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Autoimmune Diseases
Volume 2012 (2012), Article ID 189096, 16 pages
http://dx.doi.org/10.1155/2012/189096
Review Article

CD8+ T-Cell Deficiency, Epstein-Barr Virus Infection, Vitamin D Deficiency, and Steps to Autoimmunity: A Unifying Hypothesis

1School of Medicine, The University of Queensland, Brisbane, QLD 4072, Australia
2Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane, QLD 4029, Australia

Received 18 August 2011; Revised 3 October 2011; Accepted 16 October 2011

Academic Editor: Corrado Betterle

Copyright © 2012 Michael P. Pender. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. S. Evans, N. F. Rothfield, and J. C. Niederman, “Raised antibody titres to E.B. virus in systemic lupus erythematosus,” The Lancet, vol. 1, no. 7691, pp. 167–168, 1971. View at Scopus
  2. H. L. E. Lang, H. Jacobsen, S. Ikemizu et al., “A functional and structural basis for TCR cross-reactivity in multiple sclerosis,” Nature Immunology, vol. 3, no. 10, pp. 940–943, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  3. B. D. Poole, R. H. Scofield, J. B. Harley, and J. A. James, “Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus,” Autoimmunity, vol. 39, no. 1, pp. 63–70, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. J. D. Lünemann, I. Jelčić, S. Roberts et al., “EBNA1-specific T cells from patients with multiple sclerosis cross react with myelin antigens and co-produce IFN-γ and IL-2,” Journal of Experimental Medicine, vol. 205, no. 8, pp. 1763–1773, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  5. M. P. Pender, “Infection of autoreactive B lymphocytes with EBV, causing chronic autoimmune diseases,” Trends in Immunology, vol. 24, no. 11, pp. 584–588, 2003. View at Publisher · View at Google Scholar · View at Scopus
  6. G. R. Nemerow, C. Mold, V. K. Schwend, V. Tollefson, and N. R. Cooper, “Identification of gp350 as the viral glycoprotein mediating attachment of Epstein-Barr virus (EBV) to the EBV/C3d receptor of B cells: sequence homology of gp350 and C3 complement fragment C3d,” Journal of Virology, vol. 61, no. 5, pp. 1416–1420, 1987.
  7. D. A. Thorley-Lawson and A. Gross, “Persistence of the Epstein-Barr virus and the origins of associated lymphomas,” The New England Journal of Medicine, vol. 350, no. 13, pp. 1328–1337, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  8. L. L. Laichalk and D. A. Thorley-Lawson, “Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo,” Journal of Virology, vol. 79, no. 2, pp. 1296–1307, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  9. V. Hadinoto, M. Shapiro, C. C. Sun, and D. A. Thorley-Lawson, “The dynamics of EBV shedding implicate a central role for epithelial cells in amplifying viral output,” PLoS Pathogens, vol. 5, no. 7, Article ID e1000496, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. T. A. Souza, B. D. Stollar, J. L. Sullivan, K. Luzuriaga, and D. A. Thorley-Lawson, “Peripheral B cells latently infected with Epstein-Barr virus display molecular hallmarks of classical antigen-selected memory B cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 50, pp. 18093–18098, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. C. Mancao and W. Hammerschmidt, “Epstein-Barr virus latent membrane protein 2A is a B-cell receptor mimic and essential for B-cell survival,” Blood, vol. 110, no. 10, pp. 3715–3721, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. J. Rastelli, C. Hömig-Hölzel, J. Seagal et al., “LMP1 signaling can replace CD40 signaling in B cells in vivo and has unique features of inducing class-switch recombination to IgG1,” Blood, vol. 111, no. 3, pp. 1448–1455, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. J. E. Roughan and D. A. Thorley-Lawson, “The intersection of Epstein-Barr virus with the germinal center,” Journal of Virology, vol. 83, no. 8, pp. 3968–3976, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. A. D. Hislop, G. S. Taylor, D. Sauce, and A. B. Rickinson, “Cellular responses to viral infection in humans: lessons from Epstein-Barr virus,” Annual Review of Immunology, vol. 25, pp. 587–617, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  15. A. B. Rickinson and E. Kieff, “Epstein-Barr virus,” in Fields Virology. Volume 2, D. M. Knipe and P. M. Howley, Eds., pp. 2575–2627, Lippincott Williams & Wilkins, Philadelphia, Pa, USA, 4th edition, 2001.
  16. E. L. Reinherz, H. L. Weiner, and S. L. Hauser, “Loss of suppressor T cells in active multiple sclerosis. Analysis with monoclonal antibodies,” The New England Journal of Medicine, vol. 303, no. 3, pp. 125–129, 1980.
  17. M. A. Bach, E. Tournier, F. Phan-Dinh-Tuy, et al., “Deficit of suppressor T cells in active multiple sclerosis,” The Lancet, vol. 2, no. 8206, pp. 1221–1223, 1980.
  18. A. J. Thompson, J. Brazil, C. A. Whelan, E. A. Martin, M. Hutchinson, and C. Feighery, “Peripheral blood T lymphocyte changes in multiple sclerosis: a marker of disease progression rather than of relapse?” Journal of Neurology Neurosurgery and Psychiatry, vol. 49, no. 8, pp. 905–912, 1986.
  19. E. Kreuzfelder, G. Shen, M. Bittorf et al., “Enumeration of T, B and natural killer peripheral blood cells of patients with multiple sclerosis and controls,” European Neurology, vol. 32, no. 4, pp. 190–194, 1992. View at Scopus
  20. G. Michałowska-Wender and M. Wender, “Mononuclear subsets in the peripheral blood of multiple sclerosis patients in relation to results of brain gadolinium—enhancing imaging,” Folia Neuropathologica, vol. 44, no. 1, pp. 67–71, 2006. View at Scopus
  21. M. P. Pender, P. A. Csurhes, C. M. M. Pfluger, and S. R. Burrows, “Decreased CD8+T cell response to Epstein-Barr virus infected B cells in multiple sclerosis is not due to decreased HLA class I expression on B cells or monocytes,” BMC Neurology, vol. 11, article 95, 2011. View at Publisher · View at Google Scholar · View at PubMed
  22. E. M. Veys, P. Hermanns, G. Goldstein, P. Kung, J. Schindler, and J. Van Wauwe, “Determination of T lymphocyte subpopulations by monoclonal antibodies in rheumatoid arthritis. Influence of immunomodulating agents,” International Journal of Immunopharmacology, vol. 3, no. 3, pp. 313–319, 1981. View at Publisher · View at Google Scholar
  23. R. I. Fox, S. Fong, N. Sabharwal, S. A. Carstens, P. C. Kung, and J. H. Vaughan, “Synovial fluid lymphocytes differ from peripheral blood lymphocytes atients with rheumatoid arthritis,” Journal of Immunology, vol. 128, no. 1, pp. 351–354, 1982.
  24. C. Morimoto, E. L. Reinherz, S. F. Schlossman, P. H. Schur, J. A. Mills, and A. D. Steinberg, “Alterations in immunoregulatory T cell subsets in active systemic lupus erythematosus,” Journal of Clinical Investigation, vol. 66, no. 5, pp. 1171–1174, 1980.
  25. C. Morimoto, E. L. Reinherz, L. M. Nadler, J. A. Distaso, A. D. Steinberg, and S. F. Schlossman, “Comparison in T- and B-cell markers in patients with Sjögren's syndrome and systemic lupus erythematosus,” Clinical Immunology and Immunopathology, vol. 22, no. 2, pp. 270–278, 1982.
  26. R. I. Fox, S. A. Carstens, S. Fong, C. A. Robinson, F. Howell, and J. H. Vaughan, “Use of monoclonal antibodies to analyze peripheral blood and salivary gland lymphocyte subsets in Sjögren's syndrome,” Arthritis and Rheumatism, vol. 25, no. 4, pp. 419–426, 1982.
  27. T. L. Whiteside, Y. Kumagai, A. D. Roumm, R. Almendinger, and G. P. Rodnan, “Suppressor cell function and T lymphocyte subpopulations in peripheral blood of patients with progressive systemic sclerosis,” Arthritis and Rheumatism, vol. 26, no. 7, pp. 841–847, 1983.
  28. R. Gustafsson, T. H. Tötterman, L. Klareskog, and R. Hällgren, “Increase in activated T cells and reduction in suppressor inducer T cells in systemic sclerosis,” Annals of the Rheumatic Diseases, vol. 49, no. 1, pp. 40–45, 1990. View at Scopus
  29. M. R. G. O'Gorman, V. Corrochano, J. Roleck, M. Donovan, and L. M. Pachman, “Flow cytometric analyses of the lymphocyte subsets in peripheral blood of children with untreated active juvenile dermatomyositis,” Clinical and Diagnostic Laboratory Immunology, vol. 2, no. 2, pp. 205–208, 1995. View at Scopus
  30. M. Aleksza, A. Szegedi, P. Antal-Szalmás et al., “Altered cytokine expression of peripheral blood lymphocytes in polymyositis and dermatomyositis,” Annals of the Rheumatic Diseases, vol. 64, no. 10, pp. 1485–1489, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  31. R. Moreno-Otero, M. P. Civeira, T. Suou, M. E. Kanof, S. P. James, and E. A. Jones, “Reduced numbers of CD8+ T cells and B cell expression of Leu-8 antigen in peripheral blood of patients with primary biliary cirrhosis,” Hepato-Gastroenterology, vol. 41, no. 3, pp. 239–243, 1994. View at Scopus
  32. K. D. Lindor, R. H. Wiesner, and J. A. Katzmann, “Lymphocyte subsets in primary sclerosing cholangitis,” Digestive Diseases and Sciences, vol. 32, no. 7, pp. 720–725, 1987. View at Scopus
  33. N. J. Godin, D. B. Sachar, and R. Winchester, “Loss of suppressor T-cells in active inflammatory bowel disease,” Gut, vol. 25, no. 7, pp. 743–747, 1984. View at Scopus
  34. R. P. Learmonth, E. Pihl, W. R. Johnson, M. A. Barnett, F. T. McDermott, and E. S. Hughes, “Altered blood lymphocyte subclasses in patients with ulcerative colitis,” Australian and New Zealand Journal of Surgery, vol. 54, no. 3, pp. 265–269, 1984.
  35. F. Kokelj, S. Perticarari, G. Presani, and G. Trevisan, “An analysis of T-lymphocyte subpopulations in psoriasis using monoclonal antibodies,” Acta Dermato-Venereologica, vol. 63, no. 5, pp. 422–424, 1983. View at Scopus
  36. R. D'Amelio, C. Frati, A. Fattorossi, and F. Aiuti, “Peripheral T-cell subset imbalance in patients with vitiligo and in their apparently healthy first-degree relatives,” Annals of Allergy, vol. 65, no. 2, pp. 143–145, 1990. View at Scopus
  37. R. Pichler, K. Sfetsos, B. Badics, S. Gutenbrunner, J. Berg, and J. Auböck, “Lymphocyte imbalance in vitiligo patients indicated by elevated CD4+/CD8+ T-cell ratio,” Wiener Medizinische Wochenschrift, vol. 159, no. 13-14, pp. 337–341, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  38. A. Hovmark and E. Asbrink, “An immunological study of patients with bullous pemphigiod,” Acta Dermato-Venereologica, vol. 62, no. 3, pp. 201–204, 1982. View at Scopus
  39. B. Guillot, H. Laure, M. Andary et al., “Immunological studies in bullous pemphigoid: cellular immunity before and after treatment with corticosteroid and plasma exchanges,” Transfusion Science, vol. 11, no. 1, pp. 79–84, 1990. View at Publisher · View at Google Scholar · View at Scopus
  40. J. Luckac, B. Burek, and Z. Kusić, “Peripheral blood lymphocyte populations and phagocytic functions in patients with active alopecia areata,” Acta Medica Croatica, vol. 47, no. 3, pp. 113–118, 1993. View at Scopus
  41. J. E. Sanderson, D. Koech, D. Iha, and H. P. Ojiambo, “T-lymphocyte subsets in idiopathic dilated cardiomyopathy,” American Journal of Cardiology, vol. 55, no. 6, pp. 755–758, 1985. View at Scopus
  42. A. Bozkurt, A. Canataroǧlu, S. Cetiner, Y. Dönmez, A. Usal, and M. Demirtaş, “Lymphocyte subsets in patients with idiopathic dilated cardiomyopathy,” Anadolu Kardiyoloji Dergisi, vol. 1, no. 2, pp. 98–100, 2001.
  43. K. Buschard, C. Ropke, S. Madsbad, J. Mehlsen, T. B. Sørensen, and J. Rygaard, “Alterations of peripheral T-lymphocyte subpopulations in patients with insulin-dependent (type 1) diabetes mellitus,” Journal of Clinical and Laboratory Immunology, vol. 10, no. 3, pp. 127–131, 1983.
  44. A. Galluzzo, C. Giordano, G. Rubino, and G. D. Bompiani, “Immunoregulatory T-lymphocyte subset deficiency in newly diagnosed type 1 (insulin-dependent) diabetes mellitus,” Diabetologia, vol. 26, no. 6, pp. 426–430, 1984. View at Scopus
  45. C. Johnston, L. Alviggi, B. A. Millward, R. D. G. Leslie, D. A. Pyke, and D. Vergani, “Alterations in T-lymphocyte subpopulations in type I diabetes. Exploration of genetic influence in identical twins,” Diabetes, vol. 37, no. 11, pp. 1484–1488, 1988. View at Scopus
  46. S. A. Kaaba and S. A. Al-Harbi, “Abnormal lymphocyte subsets in Kuwaiti patients with type-1 insulin-dependent diabetes mellitus and their first-degree relatives,” Immunology Letters, vol. 47, no. 3, pp. 209–213, 1995. View at Publisher · View at Google Scholar · View at Scopus
  47. C. Thielemans, L. Vanhaelst, and M. De Waele, “Autoimmune thyroiditis: a condition related to a decrease in T-suppressor cells,” Clinical Endocrinology, vol. 15, no. 3, pp. 259–263, 1981. View at Scopus
  48. N. Xia, S. Zhou, Y. Liang et al., “CD4+ T cells and the Th1/Th2 imbalance are implicated in the pathogenesis of Graves' ophthalmopathy,” International Journal of Molecular Medicine, vol. 17, no. 5, pp. 911–916, 2006. View at Scopus
  49. Y. Iwatani, N. Amino, Y. Hidaka et al., “Decreases in αβ T cell receptor negative T cells and CD8 cells, and an increase in CD4+ CD8+ cells in active Hashimoto's disease and subacute thyroiditis,” Clinical and Experimental Immunology, vol. 87, no. 3, pp. 444–449, 1992. View at Scopus
  50. S. Berrih, C. Gaud, M. A. Bach, H. Le Brigand, J. P. Binet, and J. F. Bach, “Evaluation of T cell subsets in myasthenia gravis using anti-T cell monoclonal antibodies,” Clinical and Experimental Immunology, vol. 45, no. 1, pp. 1–8, 1981.
  51. P. R. Skolnik, R. P. Lisak, and B. Zweiman, “Monoclonal antibody analysis of blood T-cell subsets in myasthenia gravis,” Annals of Neurology, vol. 11, no. 2, pp. 170–176, 1982. View at Scopus
  52. L. Chatenoud and M. A. Bach, “Abnormalities of T-cell subsets in glomerulonephritis and systemic lupus erythematosus,” Kidney International, vol. 20, no. 2, pp. 267–274, 1981. View at Scopus
  53. A. Fornasieri, R. Sinico, G. Fiorini et al., “T-lymphocyte subsets in primary and secondary glomerulonephritis,” Proceedings of the European Dialysis and Transplant Association, vol. 19, pp. 635–641, 1983. View at Scopus
  54. N. Imamura, K. Fujimura, and A. Kuramoto, “Lymphocyte subpopulations in pernicious anemia,” The New England Journal of Medicine, vol. 311, no. 1, p. 56, 1984. View at Scopus
  55. C. A. Gogos, K. N. Kapatais-Zoumbos, and N. C. Zoumbos, “Lymphocyte subpopulations in megaloblastic anaemia due to vitamin B-12 deficiency,” Scandinavian Journal of Haematology, vol. 37, no. 4, pp. 316–318, 1986. View at Scopus
  56. Y. Iwatani, N. Amino, H. Mori, et al., “T lymphocyte subsets in autoimmune thyroid diseases and subacute thyroiditis detected with monoclonal antibodies,” Journal of Clinical Endocrinology and Metabolism, vol. 56, no. 2, pp. 251–254, 1983.
  57. M. Bonnyns, J. Bentin, G. Devetter, and J. Duchateau, “Heterogeneity of immunoregulatory T cells in human thyroid autoimmunity: influence of thyroid status,” Clinical and Experimental Immunology, vol. 52, no. 3, pp. 629–634, 1983. View at Scopus
  58. J. Booss, M. M. Esiri, W. W. Tourtellotte, and D. Y. Mason, “Immunohistological analysis of T lymphocyte subsets in the central nervous system in chronic progressive multiple sclerosis,” Journal of the Neurological Sciences, vol. 62, no. 1-3, pp. 219–232, 1983. View at Scopus
  59. Y. Hoshino, T. Morishima, H. Kimura, K. Nishikawa, T. Tsurumi, and K. Kuzushima, “Antigen-driven expansion and contraction of CD8+-activated T cells in primary EBV infection,” Journal of Immunology, vol. 163, no. 10, pp. 5735–5740, 1999. View at Scopus
  60. M. Yajima, K. I. Imadome, A. Nakagawa et al., “A new humanized mouse model of Epstein-Barr virus infection that reproduces persistent infection, lymphoproliferative disorder, and cell-mediated and humoral immune responses,” Journal of Infectious Diseases, vol. 198, no. 5, pp. 673–682, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. T. Strowig, C. Gurer, A. Ploss et al., “Priming of protective T cell responses against virus-induced tumors in mice with human immune system components,” Journal of Experimental Medicine, vol. 206, no. 6, pp. 1423–1434, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. A. Amadori, R. Zamarchi, G. De Silvestro et al., “Genetic control of the CD4/CD8 T-cell ratio in humans,” Nature Medicine, vol. 1, no. 12, pp. 1279–1283, 1995. View at Scopus
  63. M. A. R. Ferreira, M. Mangino, C. J. Brumme et al., “Quantitative trait loci for CD4:CD8 lymphocyte ratio are associated with risk of type 1 diabetes and HIV-1 immune control,” American Journal of Human Genetics, vol. 86, no. 1, pp. 88–92, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  64. D. A. Jabs, F. C. Arnett, W. B. Bias, and M. G. Beale, “Familial abnormalities of lymphocyte function in a large Sjögren's syndrome kindred,” Journal of Rheumatology, vol. 13, no. 2, pp. 320–326, 1986. View at Scopus
  65. M. Johansen, P. Elling, H. Elling, and A. Olsson, “A genetic approach to the aetiology of giant cell arteritis: depletion of the CD8+ T-lymphocyte subset in relatives of patients with polymyalgia rheumatica and arteritis temporalis,” Clinical and Experimental Rheumatology, vol. 13, no. 6, pp. 745–748, 1995. View at Scopus
  66. S. B. Tugume, E. M. Piwowar, T. Lutalo et al., “Hematological reference ranges among healthy Ugandans,” Clinical and Diagnostic Laboratory Immunology, vol. 2, no. 2, pp. 233–235, 1995.
  67. D. Menard, M. J. Mandeng, M. B. Tothy, E. K. Kelembho, G. Gresenguet, and A. Talarmin, “Immunohematological reference ranges for adults from the Central African Republic,” Clinical and Diagnostic Laboratory Immunology, vol. 10, no. 3, pp. 443–445, 2003. View at Publisher · View at Google Scholar · View at Scopus
  68. S. S. Uppal, S. Verma, and P. S. Dhot, “Normal values of CD4 and CD8 lymphocyte subsets in healthy Indian adults and the effects of sex, age, ethnicity, and smoking,” Cytometry Part B, vol. 52, no. 1, pp. 32–36, 2003. View at Scopus
  69. W. Jiang, L. Kang, H. Z. Lu et al., “Normal values for CD4 and CD8 lymphocyte subsets in healthy Chinese adults from Shanghai,” Clinical and Diagnostic Laboratory Immunology, vol. 11, no. 4, pp. 811–813, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  70. K. Jentsch-Ullrich, M. Koenigsmann, M. Mohren, and A. Franke, “Lymphocyte subsets' reference ranges in an age- and gender-balanced population of 100 healthy adults—a monocentric German study,” Clinical Immunology, vol. 116, no. 2, pp. 192–197, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  71. P. C. Ho, G. W. K. Tang, and J. W. M. Lawton, “Lymphocyte subsets in patients with oestrogen deficiency,” Journal of Reproductive Immunology, vol. 20, no. 1, pp. 85–91, 1991. View at Publisher · View at Google Scholar · View at Scopus
  72. W. M. Comans-Bitter, R. de Groot, R. van den Beemd et al., “Immunophenotyping of blood lymphocytes in childhood: reference values for lymphocyte subpopulations,” Journal of Pediatrics, vol. 130, no. 3, pp. 388–393, 1997. View at Publisher · View at Google Scholar · View at Scopus
  73. M. A. Hall, K. R. Ahmadi, P. Norman et al., “Genetic influence on peripheral blood T lymphocyte levels,” Genes and Immunity, vol. 1, no. 7, pp. 423–427, 2000. View at Scopus
  74. M. P. Pender, P. A. Csurhes, C. M. M. Pfluger, and S. R. Burrows, “CD8 T cell deficiency impairs control of Epstein-Barr virus and worsens with age in multiple sclerosis,” Journal of Neurology, Neurosurgery and Psychiatry. In press. View at Publisher · View at Google Scholar · View at PubMed
  75. P. Hersey, M. Bradley, E. Hasic, G. Haran, A. Edwards, and W. H. McCarthy, “Immunological effects of solarium exposure,” The Lancet, vol. 1, no. 8324, pp. 545–548, 1983.
  76. P. Hersey, G. Haran, E. Hasic, and A. Edwards, “Alteration of T cell subsets and induction of suppressor T cell activity in normal subjects after exposure to sunlight,” Journal of Immunology, vol. 131, no. 1, pp. 171–174, 1983. View at Scopus
  77. A. Falkenbach and A. Sedlmeyer, “Travel to sunny countries is associated with changes in immunological parameters,” Photodermatology Photoimmunology and Photomedicine, vol. 13, no. 4, pp. 139–142, 1997.
  78. C. M. Veldman, M. T. Cantorna, and H. F. DeLuca, “Expression of 1,25-dihydroxyvitamin D3 receptor in the immune system,” Archives of Biochemistry and Biophysics, vol. 374, no. 2, pp. 334–338, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  79. B. J. Nonnecke, S. T. Franklin, T. A. Reinhardt, and R. L. Horst, “In vitro modulation of proliferation and phenotype of resting and mitogen-stimulated bovine mononuclear leukocytes by 1,25-dihydroxyvitamin D3,” Veterinary Immunology and Immunopathology, vol. 38, no. 1-2, pp. 75–89, 1993. View at Publisher · View at Google Scholar · View at Scopus
  80. I. Žofková and R. L. Kancheva, “The effect of 1,25(OH)2 vitamin D3 on CD4+/CD8+ subsets of T lymphocytes in postmenopausal women,” Life Sciences, vol. 61, no. 2, pp. 147–152, 1997. View at Publisher · View at Google Scholar · View at Scopus
  81. F. N. Çakmak, M. Erol, P. Ergül, and A. Yalçýner, “T lymphocytes and vitamins,” Journal of Pediatrics, vol. 135, no. 4, p. 531, 1999. View at Scopus
  82. G. Ulett, “Geographic distribution of multiple sclerosis,” Diseases of the Nervous System, vol. 9, no. 11, pp. 342–346, 1948.
  83. J. A. Staples, A. L. Ponsonby, L. L. Y. Lim, and A. J. McMichael, “Ecologic analysis of some immune-related disorders, including type 1 diabetes, in Australia: latitude, regional ultraviolet radiation, and disease prevalence,” Environmental Health Perspectives, vol. 111, no. 4, pp. 518–523, 2003. View at Scopus
  84. V. M. Vieira, J. E. Hart, T. F. Webster et al., “Association between residences in U.S. northern latitudes and rheumatoid arthritis: a spatial analysis of the nurses' health study,” Environmental Health Perspectives, vol. 118, no. 7, pp. 957–961, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  85. K. L. Munger, L. I. Levin, B. W. Hollis, N. S. Howard, and A. Ascherio, “Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis,” Journal of the American Medical Association, vol. 296, no. 23, pp. 2832–2838, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  86. Y. Arnson, H. Amital, N. Agmon-Levin et al., “Serum 25-OH vitamin D concentrations are linked with various clinical aspects in patients with systemic sclerosis: a retrospective cohort study and review of the literature,” Autoimmunity Reviews, vol. 10, no. 8, pp. 490–494, 2011. View at Publisher · View at Google Scholar · View at PubMed
  87. E. Peelen, S. Knippenberg, A.-H. Muris et al., “Effects of vitamin D on the peripheral adaptive immune system: a review,” Autoimmunity Reviews, vol. 10, no. 12, pp. 733–743, 2011. View at Publisher · View at Google Scholar · View at PubMed
  88. S. Haahr and P. Höllsberg, “Multiple sclerosis is linked to Epstein-Barr virus infection,” Reviews in Medical Virology, vol. 16, no. 5, pp. 297–310, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  89. P. F. Bray, L. C. Bloomer, and V. C. Salmon, “Epstein-Barr virus infection and antibody synthesis in patients with multiple sclerosis,” Archives of Neurology, vol. 40, no. 7, pp. 406–408, 1983.
  90. K. P. Wandinger, W. Jabs, A. Siekhaus et al., “Association between clinical disease activity and Epstein-Barr virus reactivation in MS,” Neurology, vol. 55, no. 2, pp. 178–184, 2000. View at Scopus
  91. A. Ascherio and K. L. Munger, “Environmental risk factors for multiple sclerosis. Part I: the role of infection,” Annals of Neurology, vol. 61, no. 4, pp. 288–299, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  92. L. I. Levin, K. L. Munger, E. J. O'Reilly, K. I. Falk, and A. Ascherio, “Primary infection with the Epstein-Barr virus and risk of multiple sclerosis,” Annals of Neurology, vol. 67, no. 6, pp. 824–830, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  93. M. P. Pender, “The essential role of Epstein-Barr virus in the pathogenesis of multiple sclerosis,” Neuroscientist, vol. 17, no. 4, pp. 351–367, 2011. View at Publisher · View at Google Scholar · View at PubMed
  94. D. Pohl, B. Krone, K. Rostasy et al., “High seroprevalence of Epstein-Barr virus in children with multiple sclerosis,” Neurology, vol. 67, no. 11, pp. 2063–2065, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  95. B. Banwell, L. Krupp, J. Kennedy et al., “Clinical features and viral serologies in children with multiple sclerosis: a multinational observational study,” The Lancet Neurology, vol. 6, no. 9, pp. 773–781, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  96. J. D. Lünemann, P. Huppke, S. Roberts, W. Brück, J. Gärtner, and C. Münz, “Broadened and elevated humoral immune response to EBNA1 in pediatric multiple sclerosis,” Neurology, vol. 71, no. 13, pp. 1033–1035, 2008. View at Publisher · View at Google Scholar · View at PubMed
  97. J. A. James, K. M. Kaufman, A. D. Farris, E. Taylor-Albert, T. J. A. Lehman, and J. B. Harley, “An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus,” Journal of Clinical Investigation, vol. 100, no. 12, pp. 3019–3026, 1997. View at Scopus
  98. J. A. James, B. R. Neas, K. L. Moser et al., “Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure,” Arthritis and Rheumatism, vol. 44, no. 5, pp. 1122–1126, 2001. View at Publisher · View at Google Scholar · View at Scopus
  99. D. Thomas, F. Karachaliou, K. Kallergi et al., “Herpes virus antibodies seroprevalence in children with autoimmune thyroid disease,” Endocrine, vol. 33, no. 2, pp. 171–175, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  100. K. Nagata, S. Fukata, K. Kanai et al., “The influence of epstein-barr virus reactivation in patients with Graves' disease,” Viral Immunology, vol. 24, no. 2, pp. 143–149, 2011. View at Publisher · View at Google Scholar · View at PubMed
  101. S. Harada, J. Greally, J. Davis et al., “Epstein-Barr virus specific antibodies in patients with coeliac disease,” Irish Journal of Medical Science, vol. 154, no. 11, pp. 416–421, 1985. View at Publisher · View at Google Scholar · View at Scopus
  102. D. Hochberg, T. Souza, M. Catalina, J. L. Sullivan, K. Luzuriaga, and D. A. Thorley-Lawson, “Acute infection with Epstein-Barr virus targets and overwhelms the peripheral memory B-cell compartment with resting, latently infected cells,” Journal of Virology, vol. 78, no. 10, pp. 5194–5204, 2004. View at Publisher · View at Google Scholar · View at Scopus
  103. E. L. Thacker, F. Mirzaei, and A. Ascherio, “Infectious mononucleosis and risk for multiple sclerosis: a meta-analysis,” Annals of Neurology, vol. 59, no. 3, pp. 499–503, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  104. S. Haahr, A. M. Plesner, B. F. Vestergaard, and P. Höllsberg, “A role of late Epstein-Barr virus infection in multiple sclerosis,” Acta Neurologica Scandinavica, vol. 109, no. 4, pp. 270–275, 2004. View at Publisher · View at Google Scholar
  105. N. S. Crowcroft, A. Vyse, D. W. G. Brown, and D. P. Strachan, “Epidemiology of Epstein-Barr virus infection in pre-adolescent children: application of a new salivary method in Edinburgh, Scotland,” Journal of Epidemiology and Community Health, vol. 52, no. 2, pp. 101–104, 1998. View at Scopus
  106. A. Kondrashova, H. Viskari, A.-M. Haapala et al., “Serological evidence of thyroid autoimmunity among schoolchildren in two different socioeconomic environments,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 3, pp. 729–734, 2008. View at Publisher · View at Google Scholar · View at PubMed
  107. G. Tosato, A. D. Steinberg, and R. M. Blaese, “Defective EBV-specific suppressor T-cell function in rheumatoid arthritis,” The New England Journal of Medicine, vol. 305, no. 21, pp. 1238–1243, 1981. View at Scopus
  108. J. S. H. Gaston, A. B. Rickinson, and M. A. Epstein, “Epstein-Barr virus-specific cytotoxic T cell responses in rheumatoid arthritis patients,” Rheumatology International, vol. 2, no. 4, pp. 155–159, 1982. View at Scopus
  109. G. Tosato, A. D. Steinberg, R. Yarchoan, et al., “Abnormally elevated frequency of Epstein-Barr virus-infected B cells in the blood of patients with rheumatoid arthritis,” Journal of Clinical Investigation, vol. 73, no. 6, pp. 1789–1795, 1984.
  110. G. C. Tsokos, I. T. Magrath, and J. E. Balow, “Epstein-Barr virus induces normal B cell responses but defective suppressor T cell responses in patients with systemic lupus erythematosus,” Journal of Immunology, vol. 131, no. 4, pp. 1797–1801, 1983. View at Scopus
  111. S. Whittingham, J. McNeilage, and I. R. Mackay, “Primary Sjögren's syndrome after infectious mononucleosis,” Annals of Internal Medicine, vol. 102, no. 4, pp. 490–493, 1985. View at Scopus
  112. K. Yamaoka, N. Miyasaka, and K. Yamamoto, “Possible involvement of Epstein-Barr virus in polyclonal B cell activation in Sjögren's syndrome,” Arthritis and Rheumatism, vol. 31, no. 8, pp. 1014–1021, 1988. View at Scopus
  113. J. C. Craig, S. A. Hawkins, M. W. Swallow, et al., “Subsets of T lymphocytes in relation to T lymphocyte function in multiple sclerosis,” Clinical and Experimental Immunology, vol. 61, no. 3, pp. 548–555, 1985.
  114. M. P. Pender, P. A. Csurhes, A. Lenarczyk, C. M. M. Pfluger, and S. R. Burrows, “Decreased T cell reactivity to Epstein-Barr virus infected lymphoblastoid cell lines in multiple sclerosis,” Journal of Neurology, Neurosurgery and Psychiatry, vol. 80, no. 5, pp. 498–505, 2009. View at Publisher · View at Google Scholar · View at PubMed
  115. S. P. James, E. A. Jones, J. H. Hoofnagle, and W. Strober, “Circulating activated B cells in primary biliary cirrhosis,” Journal of Clinical Immunology, vol. 5, no. 4, pp. 254–260, 1985. View at Scopus
  116. A. Shore, R. Klock, P. Lee, K. M. Snow, and E. C. Keystone, “Impaired late suppression of Epstein-Barr virus (EBV)-induced immunoglobulin synthesis: a common feature of autoimmune disease,” Journal of Clinical Immunology, vol. 9, no. 2, pp. 103–110, 1989. View at Scopus
  117. J. S. Yi, M. A. Cox, and A. J. Zajac, “T-cell exhaustion: characteristics, causes and conversion,” Immunology, vol. 129, no. 4, pp. 474–481, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  118. I. Saito, B. Servenius, T. Compton, and R. I. Fox, “Detection of Epstein-Barr virus DNA by polymerase chain reaction in blood and tissue biopsies from patients with Sjögren's syndrome,” Journal of Experimental Medicine, vol. 169, no. 6, pp. 2191–2198, 1989. View at Scopus
  119. S. C. Pflugfelder, C. Crouse, I. Pereira, and S. Atherton, “Amplification of Epstein-Barr virus genomic sequences in blood cells, lacrimal glands, and tears from primary Sjögren's syndrome patients,” Ophthalmology, vol. 97, no. 8, pp. 976–984, 1990. View at Scopus
  120. N. Balandraud, J. B. Meynard, I. Auger et al., “Epstein-Barr virus load in the peripheral blood of patients with rheumatoid arthritis: accurate quantification using real-time polymerase chain reaction,” Arthritis and Rheumatism, vol. 48, no. 5, pp. 1223–1228, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  121. I. Kang, T. Quan, H. Nolasco et al., “Defective control of latent Epstein-Barr virus infection in systemic lupus erythematosus,” Journal of Immunology, vol. 172, no. 2, pp. 1287–1294, 2004. View at Scopus
  122. S. A. Morshed, M. Nishioka, I. Saito, K. Komiyama, and I. Moro, “Increased expression of Epstein-Barr virus in primary biliary cirrhosis patients,” Gastroenterologia Japonica, vol. 27, no. 6, pp. 751–758, 1992. View at Scopus
  123. S. Sankaran-Walters, K. Ransibrahmanakul, I. Grishina et al., “Epstein-Barr virus replication linked to B cell proliferation in inflamed areas of colonic mucosa of patients with inflammatory bowel disease,” Journal of Clinical Virology, vol. 50, no. 1, pp. 31–36, 2011. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  124. A. J. Gross, D. Hochberg, W. M. Rand, and D. A. Thorley-Lawson, “EBV and systemic lupus erythematosus: a new perspective,” Journal of Immunology, vol. 174, no. 11, pp. 6599–6607, 2005. View at Scopus
  125. M. A. Catalano, D. A. Carson, S. F. Slovin, D. D. Richman, and J. H. Vaughan, “Antibodies to Epstein-Barr virus-determined antigens in normal subjects and in patients with seropositive rheumatoid arthritis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 76, no. 11, pp. 5825–5828, 1979.
  126. C. V. Sumaya, L. W. Myers, and G. W. Ellison, “Epstein-Barr virus antibodies in multiple sclerosis,” Archives of Neurology, vol. 37, no. 2, pp. 94–96, 1980. View at Scopus
  127. J. M. Vergnon, G. de Thé, P. Weynants, M. Vincent, J. F. Mornex, and J. Brune, “Cryptogenic fibrosing alveolitis and Epstein-Barr virus: an association?” The Lancet, vol. 324, no. 8406, pp. 768–771, 1984.
  128. L. Origgi, C. Hu, E. Bertetti et al., “Antibodies to Epstein-Barr virus and cytomegalovirus in primary Sjögren's syndrome,” Bollettino dell'Istituto Sieroterapico Milanese, vol. 67, no. 4, pp. 265–274, 1988.
  129. P. M. Andre, P. Le Pogamp, R. Griffais, D. Chevet, and M. P. Ramee, “Is Epstein-Barr virus involved in primary IgA nephropathy?” Nephron, vol. 54, no. 2, pp. 185–186, 1990. View at Scopus
  130. J. Vrbikova, I. Janatkova, V. Zamrazil, R. Tomiska, and T. Fucikova, “Epstein-Barr virus serology in patients with autoimmune thyroiditis,” Experimental and Clinical Endocrinology and Diabetes, vol. 104, no. 1, pp. 89–92, 1996. View at Scopus
  131. A. Ascherio, K. L. Munger, E. T. Lennette et al., “Epstein-Barr virus antibodies and risk of multiple sclerosis: a prospective study,” Journal of the American Medical Association, vol. 286, no. 24, pp. 3083–3088, 2001. View at Scopus
  132. P. Sundström, P. Juto, G. Wadell et al., “An altered immune response to Epstein-Barr virus in multiple sclerosis: a prospective study,” Neurology, vol. 62, no. 12, pp. 2277–2282, 2004.
  133. L. I. Levin, K. L. Munger, M. V. Rubertone et al., “Temporal relationship between elevation of Epstein-Barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis,” Journal of the American Medical Association, vol. 293, no. 20, pp. 2496–2500, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  134. J. D. Lünemann, N. Edwards, P. A. Muraro et al., “Increased frequency and broadened specificity of latent EBV nuclear antigen-1-specific T cells in multiple sclerosis,” Brain, vol. 129, no. 6, pp. 1493–1506, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  135. G. J. Babcock, L. L. Decker, R. B. Freeman, and D. A. Thorley-Lawson, “Epstein-Barr virus-infected resting memory B cells, not proliferating lymphoblasts, accumulate in the peripheral blood of immunosuppressed patients,” Journal of Experimental Medicine, vol. 190, no. 4, pp. 567–576, 1999. View at Publisher · View at Google Scholar · View at Scopus
  136. M. L. Gulley and W. Tang, “Laboratory assays for Epstein-Barr virus-related disease,” Journal of Molecular Diagnostics, vol. 10, no. 4, pp. 279–292, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  137. T. Spieker and H. Herbst, “Distribution and phenotype of Epstein-Barr virus-infected cells in inflammatory bowel disease,” American Journal of Pathology, vol. 157, no. 1, pp. 51–57, 2000. View at Scopus
  138. S. C. Pflugfelder, C. A. Crouse, D. Monroy, M. Yen, M. Rowe, and S. S. Atherton, “Epstein-Barr virus and the lacrimal gland pathology of Sjögren's syndrome,” American Journal of Pathology, vol. 143, no. 1, pp. 49–64, 1993. View at Scopus
  139. S. Wen, N. Shimizu, H. Yoshiyama, Y. Mizugaki, F. Shinozaki, and K. Takada, “Association of Epstein-Barr virus (EBV) with Sjögren's syndrome: differential EBV expression between epithelial cells and lymphocytes in salivary glands,” American Journal of Pathology, vol. 149, no. 5, pp. 1511–1517, 1996. View at Scopus
  140. H. Yanai, N. Shimizu, S. Nagasaki, N. Mitani, and K. Okita, “Epstein-Barr virus infection of the colon with inflammatory bowel disease,” American Journal of Gastroenterology, vol. 94, no. 6, pp. 1582–1586, 1999. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  141. B. Serafini, B. Rosicarelli, D. Franciotta et al., “Dysregulated Epstein-Barr virus infection in the multiple sclerosis brain,” Journal of Experimental Medicine, vol. 204, no. 12, pp. 2899–2912, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  142. P. Cavalcante, B. Serafini, B. Rosicarelli et al., “Epstein-Barr virus persistence and reactivation in myasthenia gravis thymus,” Annals of Neurology, vol. 67, no. 6, pp. 726–738, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  143. H. Iwama, S. Horikoshi, I. Shirato, and Y. Tomino, “Epstein-Barr virus detection in kidney biopsy specimens correlates with glomerular mesangial injury,” American Journal of Kidney Diseases, vol. 32, no. 5, pp. 785–793, 1998. View at Scopus
  144. J. P. Stewart, J. J. Egan, A. J. Ross et al., “The detection of Epstein-Barr virus DNA in lung tissue from patients with idiopathic pulmonary fibrosis,” American Journal of Respiratory and Critical Care Medicine, vol. 159, no. 4, pp. 1336–1341, 1999. View at Scopus
  145. R. W. Hoffman, “T cells in the pathogenesis of systemic lupus erythematosus,” Clinical Immunology, vol. 113, no. 1, pp. 4–13, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  146. S. Matsubayashi, H. Tamai, T. Morita et al., “Hashimoto's thyroiditis manifesting monoclonal lymphocytic infiltration,” Clinical and Experimental Immunology, vol. 79, no. 2, pp. 170–174, 1990. View at Scopus
  147. J. L. Pablos, P. E. Carreira, L. Morillas, G. Montalvo, C. Ballestin, and J. J. Gomez-Reino, “Clonally expanded lymphocytes in the minor salivary glands of Sjögren's syndrome patients without lymphoproliferative disease,” Arthritis and Rheumatism, vol. 37, no. 10, pp. 1441–1444, 1994. View at Publisher · View at Google Scholar · View at Scopus
  148. D. I. Stott, F. Hiepe, M. Hummel, G. Steinhauser, and C. Berek, “Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sjögren's syndrome,” Journal of Clinical Investigation, vol. 102, no. 5, pp. 938–946, 1998. View at Scopus
  149. A. Gause, K. Gundlach, M. Zdichavsky et al., “The B lymphocyte in rheumatoid arthritis: analysis of rearranged Vκ genes from B cells infiltrating the synovial membrane,” European Journal of Immunology, vol. 25, no. 10, pp. 2775–2782, 1995. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  150. A. E. Schröder, A. Greiner, C. Seyfert, and C. Berek, “Differentiation of B cells in the nonlymphoid tissue of the synovial membrane of patients with rheumatoid arthritis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 1, pp. 221–225, 1996. View at Publisher · View at Google Scholar · View at Scopus
  151. Y. Qin, P. Duquette, Y. Zhang, P. Talbot, R. Poole, and J. Antel, “Clonal expansion and somatic hypermutation of VH genes of B cells from cerebrospinal fluid in multiple sclerosis,” Journal of Clinical Investigation, vol. 102, no. 5, pp. 1045–1050, 1998. View at Scopus
  152. T. Sugimura, S. Shiokawa, S. Haraoka et al., “Local antigen-driven oligoclonal expansion of B cells in the liver portal areas of patients with primary biliary cirrhosis,” Liver International, vol. 23, no. 5, pp. 323–328, 2003. View at Scopus
  153. E. M. Bradshaw, A. Orihuela, S. L. McArdel et al., “A local antigen-driven humoral response is present in the inflammatory myopathies,” Journal of Immunology, vol. 178, no. 1, pp. 547–556, 2007. View at Scopus
  154. P. P. Sfikakis, V. Karali, K. Lilakos, G. Georgiou, and P. Panayiotidis, “Clonal expansion of B-cells in human systemic lupus erythematosus: evidence from studies before and after therapeutic B-cell depletion,” Clinical Immunology, vol. 132, no. 1, pp. 19–31, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  155. S. M. McLachlan, A. M. Dickinson, and A. Malcolm, “Thyroid autoantibody synthesis by cultures of thyroid and peripheral blood lymphocytes. I. Lymphocyte markers and response to pokeweed mitogen,” Clinical and Experimental Immunology, vol. 52, no. 1, pp. 45–53, 1983.
  156. M. P. Armengol, M. Juan, A. Lucas-Martín et al., “Thyroid autoimmune disease: demonstration of thyroid antigen-specific B cells and recombination-activating gene expression in chemokine-containing active intrathyroidal germinal centers,” American Journal of Pathology, vol. 159, no. 3, pp. 861–873, 2001.
  157. S. Salomonsson, M. V. Jonsson, K. Skarstein et al., “Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjögren's syndrome,” Arthritis and Rheumatism, vol. 48, no. 11, pp. 3187–3201, 2003. View at Publisher · View at Google Scholar · View at PubMed
  158. A. Björkland, L. Lööf, I. Mendel-Hartvig, and T. H. Tötterman, “Primary biliary cirrhosis: high proportions of B cells in blood and liver tissue produce anti-mitochondrial antibodies of several Ig classes,” Journal of Immunology, vol. 153, no. 6, pp. 2750–2757, 1994. View at Scopus
  159. H. Wardemann, S. Yurasov, A. Schaefer, J. W. Young, E. Meffre, and M. C. Nussenzweig, “Predominant autoantibody production by early human B cell precursors,” Science, vol. 301, no. 5638, pp. 1374–1377, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  160. C. Garzelli, F. E. Taub, J. E. Scharff, B. S. Prabhakar, F. Ginsberg-Fellner, and A. L. Notkins, “Epstein-Barr virus-transformed lymphocytes produce monoclonal autoantibodies that react with antigens in multiple organs,” Journal of Virology, vol. 52, no. 2, pp. 722–725, 1984.
  161. R. Schwartz-Albiez, R. C. Monteiro, M. Rodriguez, C. J. Binder, and Y. Shoenfeld, “Natural antibodies, intravenous immunoglobulin and their role in autoimmunity, cancer and inflammation,” Clinical and Experimental Immunology, vol. 158, no. 1, pp. 43–50, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  162. M. Londei, G. F. Bottazzo, and M. Feldmann, “Human T-cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells,” Science, vol. 228, no. 4695, pp. 85–89, 1985. View at Scopus
  163. C. M. Dayan, M. Londei, A. E. Corcoran et al., “Autoantigen recognition by thyroid-infiltrating T cells in Graves disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 16, pp. 7415–7419, 1991. View at Scopus
  164. S. Shimoda, J. van de Water, A. Ansari et al., “Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis,” Journal of Clinical Investigation, vol. 102, no. 10, pp. 1831–1840, 1998. View at Scopus
  165. H. Kita, S. Matsumura, X. S. He et al., “Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis,” Journal of Clinical Investigation, vol. 109, no. 9, pp. 1231–1240, 2002. View at Publisher · View at Google Scholar · View at Scopus
  166. T. Namekawa, K. Kuroda, T. Kato et al., “Identification of Ro(SSA) 52 kDa reactive T cells in labial salivary glands from patients with Sjögren's syndrome,” Journal of Rheumatology, vol. 22, no. 11, pp. 2092–2099, 1995. View at Scopus
  167. Ø. Molberg, S. N. Mcadam, R. Körner et al., “Tissue transglutaminase selectively modifies gliadin peptides that are recognized by gut-derived T cells in celiac disease,” Nature Medicine, vol. 4, no. 6, pp. 713–717, 1998. View at Publisher · View at Google Scholar
  168. Z. Tabi, P. A. McCombe, and M. P. Pender, “Apoptotic elimination of Vβ8.2+ cells from the central nervous system during recovery from experimental autoimmune encephalomyelitis induced by the passive transfer of Vβ8.2+ encephalitogenic T cells,” European Journal of Immunology, vol. 24, no. 11, pp. 2609–2617, 1994. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  169. M. P. Pender, “Genetically determined failure of activation-induced apoptosis of autoreactive T cells as a cause of multiple sclerosis,” The Lancet, vol. 351, no. 9107, pp. 978–981, 1998. View at Publisher · View at Google Scholar · View at Scopus
  170. G. Hadfield, “The primary histological lesion of regional ileitis,” The Lancet, vol. 234, no. 6058, pp. 773–776, 1939. View at Scopus
  171. H. S. Carlsen, E. S. Baekkevold, F. E. Johansen, G. Haraldsen, and P. Brandtzaeg, “B cell attracting chemokine 1 (CXCL13) and its receptor CXCR5 are expressed in normal and aberrant gut associated lymphoid tissue,” Gut, vol. 51, no. 3, pp. 364–371, 2002. View at Publisher · View at Google Scholar · View at Scopus
  172. S. Hadziyannis, P. J. Scheuer, T. Feizi, R. Naccarato, D. Doniach, and S. Sherlock, “Immunological and histological studies in primary biliary cirrhosis,” Journal of Clinical Pathology, vol. 23, no. 2, pp. 95–98, 1970. View at Scopus
  173. N. Soderstrom and A. Biorklund, “Organization of the invading lymphoid tissue in human lymphoid thyroiditis,” Scandinavian Journal of Immunology, vol. 3, no. 3, pp. 295–301, 1974.
  174. C. L. Young, T. C. Adamson, J. H. Vaughan, and R. I. Fox, “Immunohistologic characterization of synovial membrane lymphocytes in rheumatoid arthritis,” Arthritis and Rheumatism, vol. 27, no. 1, pp. 32–39, 1984. View at Scopus
  175. I. Randen, O. J. Mellbye, O. Forre, and J. B. Natvig, “The identification of germinal centres and follicular dendritic cell networks in rheumatoid synovial tissue,” Scandinavian Journal of Immunology, vol. 41, no. 5, pp. 481–486, 1995.
  176. J. D. Cañete, B. Santiago, T. Cantaert et al., “Ectopic lymphoid neogenesis in psoriatic arthritis,” Annals of the Rheumatic Diseases, vol. 66, no. 6, pp. 720–726, 2007. View at Publisher · View at Google Scholar · View at PubMed
  177. D. A. Campbell, L. W. Poulter, G. Janossy, and R. M. Du Bois, “Immunohistological analysis of lung tissue from patients with cryptogenic fibrosing alveolitis suggesting local expression of immune hypersensitivity,” Thorax, vol. 40, no. 6, pp. 405–411, 1985. View at Scopus
  178. W. A. H. Wallace, S. E. M. Howie, A. S. Krajewski, and D. Lamb, “The immunological architecture of B-lymphocyte aggregates in cryptogenic fibrosing alveolitis,” Journal of Pathology, vol. 178, no. 3, pp. 323–329, 1996. View at Publisher · View at Google Scholar · View at Scopus
  179. N. Amft, S. J. Curnow, D. Scheel-Toellner et al., “Ectopic expression of the B cell-attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sjögren's syndrome,” Arthritis and Rheumatism, vol. 44, no. 11, pp. 2633–2641, 2001. View at Publisher · View at Google Scholar · View at Scopus
  180. B. Serafini, B. Rosicarelli, R. Magliozzi, E. Stigliano, and F. Aloisi, “Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis,” Brain Pathology, vol. 14, no. 2, pp. 164–174, 2004. View at Scopus
  181. R. Magliozzi, O. Howell, A. Vora et al., “Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology,” Brain, vol. 130, no. 4, pp. 1089–1104, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  182. C. D. Cohen, N. Calvaresi, S. Armelloni et al., “CD20-positive infiltrates in human membranous glomerulonephritis,” Journal of Nephrology, vol. 18, no. 3, pp. 328–333, 2005. View at Scopus
  183. F. Heller, M. T. Lindenmeyer, C. D. Cohen et al., “The contribution of B cells to renal interstitial inflammation,” American Journal of Pathology, vol. 170, no. 2, pp. 457–468, 2007. View at Publisher · View at Google Scholar · View at PubMed
  184. C. M. L. De Padilla, A. N. Vallejo, D. Lacomis, K. Mcnallan, and A. M. Reed, “Extranodal lymphoid microstructures in inflamed muscle and disease severity of new-onset juvenile dermatomyositis,” Arthritis and Rheumatism, vol. 60, no. 4, pp. 1160–1172, 2009. View at Publisher · View at Google Scholar · View at PubMed
  185. G. D. Levine and J. Rosai, “Thymic hyperplasia and neoplasia: a review of current concepts,” Human Pathology, vol. 9, no. 5, pp. 495–515, 1978. View at Scopus
  186. J. A. Thomas, H. N. A. Willcox, and J. Newsom-Davis, “Immunohistological studies of the thymus in myasthenia gravis. Correlation with clinical state and thymocyte culture responses,” Journal of Neuroimmunology, vol. 3, no. 4, pp. 319–335, 1982. View at Publisher · View at Google Scholar · View at Scopus
  187. I. Roxanis, K. Micklem, J. McConville, J. Newsom-Davis, and N. Willcox, “Thymic myoid cells and germinal center formation in myasthenia gravis; possible roles in pathogenesis,” Journal of Neuroimmunology, vol. 125, no. 1-2, pp. 185–197, 2002. View at Publisher · View at Google Scholar · View at Scopus
  188. M. Kojima, S. Nakamura, Y. Morishita et al., “Reactive follicular hyperplasia in the lymph node lesions from systemic lupus erythematosus patients: a clinicopathological and immunohistological study of 21 cases,” Pathology International, vol. 50, no. 4, pp. 304–312, 2000. View at Publisher · View at Google Scholar · View at Scopus
  189. A. D. Sadovnick, “Genetic background of multiple sclerosis,” Autoimmunity Reviews, vol. 11, no. 3, pp. 163–166, 2012. View at Publisher · View at Google Scholar · View at PubMed
  190. E. Ballestar, “Epigenetic alterations in autoimmune rheumatic diseases,” Nature Reviews Rheumatology, vol. 7, no. 5, pp. 263–271, 2011. View at Publisher · View at Google Scholar · View at PubMed
  191. W. B. Bias, J. D. Reveille, T. H. Beaty, D. A. Meyers, and F. C. Arnett, “Evidence that autoimmunity in man is a Mendelian dominant trait,” American Journal of Human Genetics, vol. 39, no. 5, pp. 584–602, 1986.
  192. P. A. McCombe, J. B. Chalk, and M. P. Pender, “Familial occurrence of multiple sclerosis with thyroid disease and systemic lupus erythematosus,” Journal of the Neurological Sciences, vol. 97, no. 2-3, pp. 163–171, 1990. View at Publisher · View at Google Scholar · View at Scopus
  193. J. P. Lin, J. M. Cash, S. Z. Doyle et al., “Familial clustering of rheumatoid arthritis with other autoimmune diseases,” Human Genetics, vol. 103, no. 4, pp. 475–482, 1998. View at Publisher · View at Google Scholar · View at Scopus
  194. R. D. Henderson, C. J. Bain, and M. P. Pender, “The occurrence of autoimmune diseases in patients with multiple sclerosis and their families,” Journal of Clinical Neuroscience, vol. 7, no. 5, pp. 434–437, 2000. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  195. L. F. Barcellos, B. B. Kamdar, P. P. Ramsay et al., “Clustering of autoimmune diseases in families with a high-risk for multiple sclerosis: a descriptive study,” The Lancet Neurology, vol. 5, no. 11, pp. 924–931, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  196. E. Thorsby and B. A. Lie, “HLA associated genetic predisposition to autoimmune diseases: genes involved and possible mechanisms,” Transplant Immunology, vol. 14, no. 3-4, pp. 175–182, 2005. View at Publisher · View at Google Scholar · View at PubMed
  197. M. P. Pender, “Does Epstein-Barr virus infection in the brain drive the development of multiple sclerosis,” Brain, vol. 132, no. 12, pp. 3196–3198, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  198. M. P. Pender, “Preventing and curing multiple sclerosis by controlling Epstein-Barr virus infection,” Autoimmunity Reviews, vol. 8, no. 7, pp. 563–568, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  199. E. M. Sokal, K. Hoppenbrouwers, C. Vandermeulen et al., “Recombinant gp350 vaccine for infectious mononucleosis: a phase 2, randomized, double-blind, placebo-controlled trial to evaluate the safety, immunogenicity, and efficacy of an Epstein-Barr virus vaccine in healthy young adults,” Journal of Infectious Diseases, vol. 196, no. 12, pp. 1749–1753, 2007. View at Publisher · View at Google Scholar · View at PubMed
  200. T. Haque, I. Johannessen, D. Dombagoda et al., “A mouse monoclonal antibody against Epstein-Barr virus envelope glycoprotein 350 prevents infection both in Vitro and in Vivo,” Journal of Infectious Diseases, vol. 194, no. 5, pp. 584–587, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  201. B. Savoldo, J. A. Goss, M. M. Hammer et al., “Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs),” Blood, vol. 108, no. 9, pp. 2942–2949, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  202. S. G. Nanjappa, E. H. Kim, and M. Suresh, “Immunotherapeutic effects of IL-7 during a chronic viral infection in mice,” Blood, vol. 117, no. 19, pp. 5123–5132, 2011. View at Publisher · View at Google Scholar · View at PubMed
  203. Y. P. Mei, X. F. Zhu, J. M. Zhou, H. Huang, R. Deng, and Y. X. Zeng, “siRNA targeting LMP1-induced apoptosis in EBV-positive lymphoma cells is associated with inhibition of telomerase activity and expression,” Cancer Letters, vol. 232, no. 2, pp. 189–198, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  204. N. Li, S. Thompson, D. C. Schultz et al., “Discovery of selective inhibitors against EBNA1 via high throughput in silico virtual screening,” PLoS One, vol. 5, no. 4, Article ID e10126, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  205. D. H. Dreyfus, “Autoimmune disease: a role for new anti-viral therapies?” Autoimmunity Reviews, vol. 11, no. 2, pp. 88–97, 2011. View at Publisher · View at Google Scholar · View at PubMed
  206. B. Jin, H. Ni, Q. Geshang, Y. Li, W. Shen, and H. Shi, “HLA-DR4 antigen and idiopathic dilated cardiomyopathy susceptibility: a meta-analysis involving 11,761 subjects,” Tissue Antigens, vol. 77, no. 2, pp. 107–111, 2011. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  207. P. Invernizzi, C. Selmi, F. Poli et al., “Human leukocyte antigen polymorphisms in Italian primary biliary cirrhosis: a multicenter study of 664 patients and 1992 healthy controls,” Hepatology, vol. 48, no. 6, pp. 1906–1912, 2008. View at Publisher · View at Google Scholar · View at PubMed
  208. T. Ahmad, S. E. Marshall, and D. Jewell, “Genetics of inflammatory bowel disease: the role of the HLA complex,” World Journal of Gastroenterology, vol. 12, no. 23, pp. 3628–3635, 2006. View at Scopus