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Multiple Sclerosis International
Volume 2011, Article ID 423971, 9 pages
http://dx.doi.org/10.1155/2011/423971
Review Article

Potential Impact of B Cells on T Cell Function in Multiple Sclerosis

Departments of Neurology, Neurotherapeutics and Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA

Received 13 October 2010; Accepted 13 January 2011

Academic Editor: Angelo Ghezzi

Copyright © 2011 Sara Ireland and Nancy Monson. 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. Y. Yang, J. Weiner, Y. Liu et al., “T-bet is essential for encephalitogenicity of both Th1 and Th17 cells,” Journal of Experimental Medicine, vol. 206, no. 7, pp. 1549–1564, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. I. M. Stromnes, L. M. Cerretti, D. Liggitt et al., “Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells,” Nature Medicine, vol. 14, no. 3, pp. 337–342, 2008. View at Google Scholar
  3. M. Sospedra and R. Martin, “Immunology of multiple sclerosis,” Annual Review of Immunology, vol. 23, pp. 683–747, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  4. A. Naess and H. Nyland, “Multiple sclerosis. T lymphocytes in cerebrospinal fluid and blood,” European Neurology, vol. 17, no. 2, pp. 61–66, 1978. View at Google Scholar · View at Scopus
  5. C. J. Hedegaard, M. Krakauer, K. Bendtzen, H. Lund, F. Sellebjerg, and C. H. Nielsen, “T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis,” Immunology, vol. 125, no. 2, pp. 161–169, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  6. M. El-behi, A. Rostami, and B. Ciric, “Current views on the roles of Th1 and Th17 cells in experimental autoimmune encephalomyelitis,” Journal of Neuroimmune Pharmacology, vol. 5, no. 2, pp. 189–197, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. M. Sandberg Wollheim, “Immunoglobulin synthesis in vitro by cerebrospinal fluid cells in patients with meningoencephalitis of presumed viral origin,” Scandinavian Journal of Immunology, vol. 4, no. 7, pp. 617–622, 1975. View at Google Scholar · View at Scopus
  8. J. W. Prineas and R. G. Wright, “Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis,” Laboratory Investigation, vol. 38, no. 4, pp. 409–421, 1978. View at Google Scholar · View at Scopus
  9. R. P. Lisak, A. I. Levinson, B. Zweiman, and N. I. Abdou, “T and B lymphocytes in multiple sclerosis,” Clinical and Experimental Immunology, vol. 22, no. 1, pp. 30–34, 1975. View at Google Scholar · View at Scopus
  10. T. Holmøy, “The discovery of oligoclonal bands: a 50-year anniversary,” European Neurology, vol. 62, no. 5, pp. 311–315, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  11. H. F. McFarland, “The B cell—old player, new position on the team,” The New England Journal of Medicine, vol. 358, no. 7, pp. 664–665, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  12. S. L. Hauser, E. Waubant, D. L. Arnold et al., “B-cell depletion with rituximab in relapsing-remitting multiple sclerosis,” The New England Journal of Medicine, vol. 358, no. 7, pp. 676–688, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. H. F. Petereit, W. Moeller-Hartmann, D. Reske, and A. Rubbert, “Rituximab in a patient with multiple sclerosis—effect on B cells, plasma cells and intrathecal IgG synthesis,” Acta Neurologica Scandinavica, vol. 117, no. 6, pp. 399–403, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. S. Corinti, D. Medaglini, C. Prezzi, A. Cavani, G. Pozzi, and G. Girolomoni, “Human dendritic cells are superior to B cells at presenting a major histocompatibility complex class II-restricted heterologous antigen expressed on recombinant Streptococcus gordonii,” Infection and Immunity, vol. 68, no. 4, pp. 1879–1883, 2000. View at Publisher · View at Google Scholar · View at Scopus
  15. T. Issekutz, E. Chu, and R. S. Geha, “Antigen presentation by human B cells: T cell proliferation induced by Epstein Barr virus B lymphoblastoid cells,” The Journal of Immunology, vol. 129, no. 4, pp. 1446–1450, 1982. View at Google Scholar
  16. K. L. Good, D. T. Avery, and S. G. Tangye, “Resting human memory B cells are intrinsically programmed for enhanced survival and responsiveness to diverse stimuli compared to naive B cells,” The Journal of Immunology, vol. 182, no. 2, pp. 890–901, 2009. View at Google Scholar
  17. T. Holmøy and F. Vartdal, “Cerebrospinal fluid T cells from multiple sclerosis patients recognize autologous Epstein-Barr virus-transformed B cells,” Journal of NeuroVirology, vol. 10, no. 1, pp. 52–56, 2004. View at Publisher · View at Google Scholar · View at Scopus
  18. A. Bar-Or, E. M. L. Oliveira, D. E. Anderson et al., “Immunological memory: contribution of memory B cells expressing costimulatory molecules in the resting state,” Journal of Immunology, vol. 167, no. 10, pp. 5669–5677, 2001. View at Google Scholar · View at Scopus
  19. O. Chan, M. P. Madaio, and M. J. Shlomchik, “The roles of B cells in MRL/lpr murine lupus,” Annals of the New York Academy of Sciences, vol. 815, pp. 75–87, 1997. View at Publisher · View at Google Scholar · View at Scopus
  20. O. Chan, M. P. Madaio, and M. J. Shlomchik, “The roles of B cells in MRL/lpr murine lupus,” Annals of the New York Academy of Sciences, vol. 815, pp. 75–87, 1997. View at Google Scholar
  21. A. Crawford, M. MacLeod, T. Schumacher, L. Corlett, and D. Gray, “Primary T cell expansion and differentiation in vivo requires antigen presentation by B cells,” Journal of Immunology, vol. 176, no. 6, pp. 3498–3506, 2006. View at Google Scholar · View at Scopus
  22. S. K. O'Neill, M. J. Shlomchik, T. T. Glant, Y. Cao, P. D. Doodes, and A. Finnegan, “Antigen-specific B cells are required as APCs and autoantibody-producing cells for induction of severe autoimmune arthritis,” Journal of Immunology, vol. 174, no. 6, pp. 3781–3788, 2005. View at Google Scholar · View at Scopus
  23. F. S. Wong, LI. Wen, M. Tang et al., “Investigation of the role of B-cells in type 1 diabetes in the NOD mouse,” Diabetes, vol. 53, no. 10, pp. 2581–2587, 2004. View at Publisher · View at Google Scholar · View at Scopus
  24. D. E. Evans, M. W. Munks, J. M. Purkerson, and D. C. Parker, “Resting B lymphocytes as APC for naive T lymphocytes: dependence on CD40 ligand/CD40,” Journal of Immunology, vol. 164, no. 2, pp. 688–697, 2000. View at Google Scholar · View at Scopus
  25. J. I. Krieger, S. F. Grammer, H. M. Grey, and R. W. Chesnut, “Antigen presentation by splenic B cells: resting B cells are ineffective, whereas activated B cells are effective accessory cells for T cell responses,” Journal of Immunology, vol. 135, no. 5, pp. 2937–2945, 1985. View at Google Scholar · View at Scopus
  26. K. L. Rock, B. Benacerraf, and A. K. Abbas, “Antigen presentation by hapten-specific B lymphocytes. I. Role of surface immunoglobulin receptors,” Journal of Experimental Medicine, vol. 160, no. 4, pp. 1102–1113, 1984. View at Google Scholar · View at Scopus
  27. W. Jiang, M. M. Lederman, C. V. Harding, B. Rodriguez, R. J. Mohner, and S. F. Sieg, “TLR9 stimulation drives naïve B cells to proliferate and to attain enhanced antigen presenting function,” European Journal of Immunology, vol. 37, no. 8, pp. 2205–2213, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. C. T. Harp, A. E. Lovett-Racke, M. K. Racke, E. M. Frohman, and N. L. Monson, “Impact of myelin-specific antigen presenting B cells on T cell activation in multiple sclerosis,” Clinical Immunology, vol. 128, no. 3, pp. 382–391, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. M. von Bergwelt-Baildon, J. L. Schultze, B. Maecker et al., “Correspondence re R. Lapointe et al., CD40-stimulated B lymphocytes pulsed with tumor antigens are effective antigen-presenting cells that can generate specific T cells,” Cancer Research, vol. 64, no. 11, pp. 4055–4056, 2004. View at Google Scholar
  30. R. Lapointe, A. Bellemare-Pelletier, F. Housseau, J. Thibodeau, and P. Hwu, “CD40-stimulated B lymphocytes pulsed with tumor antigens are effective antigen-presenting cells that can generate specific T cells,” Cancer Research, vol. 63, no. 11, pp. 2836–2843, 2003. View at Google Scholar
  31. M. Von Bergwelt-Baildon, A. Shimabukuro-Vornhagen, A. Popov et al., “CD40-activated B cells express full lymph node homing triad and induce T-cell chemotaxis: potential as cellular adjuvants,” Blood, vol. 107, no. 7, pp. 2786–2789, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. E. J. Fuchs and P. Matzinger, “B cells turn off virgin but not memory T cells,” Science, vol. 258, no. 5085, pp. 1156–1159, 1992. View at Google Scholar · View at Scopus
  33. L. C. Chen, J. C. Delgado, P. E. Jensen, and X. Chen, “Direct expansion of human allospecific FoxP3+CD4+ regulatory T cells with allogeneic B cells for therapeutic application,” Journal of Immunology, vol. 183, no. 6, pp. 4094–4102, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  34. E. E. Eynon and D. C. Parker, “Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens,” Journal of Experimental Medicine, vol. 175, no. 1, pp. 131–138, 1992. View at Publisher · View at Google Scholar · View at Scopus
  35. P. Reichardt, B. Dornbach, S. Rong et al., “Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse,” Blood, vol. 110, no. 5, pp. 1519–1529, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. K. Attanavanich and J. F. Kearney, “Marginal zone, but not follicular B cells, are potent activators of naive CD4 T cells,” Journal of Immunology, vol. 172, no. 2, pp. 803–811, 2004. View at Google Scholar · View at Scopus
  37. T. Kakiuchi, R. W. Chesnut, and H. M. Grey, “B cells as antigen-presenting cells: the requirement for B cell activation,” Journal of Immunology, vol. 131, no. 1, pp. 109–114, 1983. View at Google Scholar · View at Scopus
  38. C. Pasare, V. Morafo, M. Entringer et al., “Presence of activated antigen-binding B cells during immunization enhances relative levels of IFN-γ in T cell responses,” Journal of Immunology, vol. 160, no. 2, pp. 778–787, 1998. View at Google Scholar · View at Scopus
  39. C. T. Harp, S. Ireland, L. S. Davis et al., “Memory B cells from a subset of treatment-naive relapsing-remitting multiple sclerosis patients elicit CD4(+) T-cell proliferation and IFN-γ production in response to myelin basic protein and myelin oligodendrocyte glycoprotein,” European Journal of Immunology, vol. 40, no. 10, pp. 2942–2956, 2010. View at Google Scholar
  40. T. Honjo, F. W. Alt, and M. S. Neuberger, Eds., Molecular Biology of B cells, Elsevier Academic Press, London, UK, 2004.
  41. K. Yanaba, J. D. Bouaziz, T. Matsushita, C. M. Magro, ST. Clair, and T. F. Tedder, “B-lymphocyte contributions to human autoimmune disease,” Immunological Reviews, vol. 223, no. 1, pp. 284–299, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  42. D. A. Dyment, G. C. Ebers, and A. D. Sadovnick, “Genetics of multiple sclerosis,” Lancet Neurology, vol. 3, no. 2, pp. 104–110, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. P. J. Perrin, C. H. June, J. H. Maldonado, R. B. Ratts, and M. K. Racke, “Blockade of CD28 during in vitro activation of encephalitogenic T cells or after disease onset ameliorates experimental autoimmune encephalomyelitis,” Journal of Immunology, vol. 163, no. 3, pp. 1704–1710, 1999. View at Google Scholar · View at Scopus
  44. L. Chen, “Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity,” Nature Reviews Immunology, vol. 4, no. 5, pp. 336–347, 2004. View at Google Scholar · View at Scopus
  45. R. W. Stuart and M. K. Racke, “Targeting T cell costimulation in autoimmune disease,” Expert Opinion on Therapeutic Targets, vol. 6, no. 3, pp. 275–289, 2002. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  46. B. Salomon and J. A. Bluestone, “Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation,” Annual Review of Immunology, vol. 19, pp. 225–252, 2001. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. K. Genç, D. L. Dona, and A. T. Reder, “Increased CD80(+) B cells in active multiple sclerosis and reversal by interferon β-1b therapy,” Journal of Clinical Investigation, vol. 99, no. 11, pp. 2664–2671, 1997. View at Google Scholar · View at Scopus
  48. S. Amu, A. Tarkowski, T. Dörner, M. Bokarewa, and M. Brisslert, “The human immunomodulatory CD25+ B cell population belongs to the memory B cell pool,” Scandinavian Journal of Immunology, vol. 66, no. 1, pp. 77–86, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. A. E. Lovett-Racke, J. L. Trotter, J. Lauber, P. J. Perrin, C. H. June, and M. K. Racke, “Decreased dependence of myelin basic protein-reactive T cells on CD28- mediated costimulation in multiple sclerosis patients,” Journal of Clinical Investigation, vol. 101, no. 4, pp. 725–730, 1998. View at Google Scholar · View at Scopus
  50. M. Comabella, D. W. Craig, M. Carmiña-Tato et al., “Identification of a novel risk locus for multiple sclerosis at 13q31.3 by a pooled genome-wide scan of 500,000 single nucleotide polymorphisms,” PLoS ONE, vol. 3, no. 10, article e3490, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  51. D. A. Dyment, B. M. Herrera, M. Z. Cader et al., “Complex interactions among MHC haplotypes in multiple sclerosis: susceptibility and resistance,” Human Molecular Genetics, vol. 14, no. 14, pp. 2019–2026, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  52. D. A. Hafler, A. Compston, S. Sawcer et al., “Risk alleles for multiple sclerosis identified by a genomewide study,” The New England Journal of Medicine, vol. 357, no. 9, pp. 851–862, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  53. G. A. Bishop and B. S. Hostager, “The CD40-CD154 interaction in B cell-T cell liaisons,” Cytokine and Growth Factor Reviews, vol. 14, no. 3-4, pp. 297–309, 2003. View at Publisher · View at Google Scholar · View at Scopus
  54. D. T. Boumpas, R. Furie, S. Manzi et al., “A short course of BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in patients with proliferative lupus glomerulonephritis,” Arthritis and Rheumatism, vol. 48, no. 3, pp. 719–727, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  55. M. Mirabet, J. A. Barrabés, A. Quiroga, and D. Garcia-Dorado, “Platelet pro-aggregatory effects of CD40L monoclonal antibody,” Molecular Immunology, vol. 45, no. 4, pp. 937–944, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. M. C. Levesque, “Translational mini-review series on B cell-directed therapies: recent advances in B cell-directed biological therapies for autoimmune disorders,” Clinical and Experimental Immunology, vol. 157, no. 2, pp. 198–208, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. E. L. Carpenter, R. Mick, J. Rüter, and R. H. Vonderheide, “Activation of human B cells by the agonist CD40 antibody CP-870,893 and augmentation with simultaneous toll-like receptor 9 stimulation,” Journal of Translational Medicine, vol. 7, article 1479, p. 93, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. F. Gantner, P. Hermann, K. Nakashima, S. Matsukawa, K. Sakai, and K. B. Bacon, “CD40-dependent and -independent activation of human tonsil B cells by CpG oligodeoxynucleotides,” European Journal of Immunology, vol. 33, no. 6, pp. 1576–1585, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  59. Y. Wang, M. Li, M. Song et al., “Expression of OX40 ligand in microglia activated by IFN-γ sustains a protective CD4+ T-cell response in vitro,” Cellular Immunology, vol. 251, no. 2, pp. 86–92, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. T. Ito, Y. H. Wang, O. Duramad et al., “0X40 ligand shuts down IL-10-producing regulatory T cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 35, pp. 13138–13143, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. J. Li, L. I. Li, X. Shang et al., “Negative regulation of IL-17 production by OX40/OX40L interaction,” Cellular Immunology, vol. 253, no. 1-2, pp. 31–37, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. K. Taga and G. Tosato, “IL-10 inhibits human T cell proliferation and IL-2 production,” Journal of Immunology, vol. 148, no. 4, pp. 1143–1148, 1992. View at Google Scholar
  63. K. W. Moore, R. de Waal Malefyt, R. L. Coffman et al., “Interleukin-10,” Annual Review of Immunology, vol. 11, pp. 165–190, 1993. View at Google Scholar
  64. K. W. Moore, R. de Waal Malefyt, R. L. Coffman et al., “Interleukin-10 and the interleukin-10 receptor,” Annual Review of Immunology, vol. 19, pp. 683–765, 2001. View at Google Scholar
  65. M. Wagner, H. Poeck, B. Jahrsdoerfer et al., “IL-12p70-dependent Th1 induction by human B cells requires combined activation with CD40 ligand and CpG DNA,” Journal of Immunology, vol. 172, no. 2, pp. 954–963, 2004. View at Google Scholar
  66. M. E. Duddy, A. Alter, and A. Bar-Or, “Distinct profiles of human B cell effector cytokines: a role in immune regulation?” Journal of Immunology, vol. 172, no. 6, pp. 3422–3427, 2004. View at Google Scholar
  67. Y. P. Rubtsov and A. Y. Rudensky, “TGFβ signalling in control of T-cell-mediated self-reactivity,” Nature Reviews Immunology, vol. 7, no. 6, pp. 443–453, 2007. View at Publisher · View at Google Scholar · View at PubMed
  68. M. O. Li, Y. Y. Wan, S. Sanjabi, A. K. L. Robertson, and R. A. Flavell, “Transforming growth factor-β regulation of immune responses,” Annual Review of Immunology, vol. 24, pp. 99–146, 2006. View at Publisher · View at Google Scholar · View at PubMed
  69. M. Veldhoen and B. Stockinger, “TGFβ1, a “Jack of all trades”: the link with pro-inflammatory IL-17-producing T cells,” Trends in Immunology, vol. 27, no. 8, pp. 358–361, 2006. View at Publisher · View at Google Scholar · View at PubMed
  70. E. Bettelli, M. Oukka, and V. K. Kuchroo, “T(H)-17 cells in the circle of immunity and autoimmunity,” Nature Immunology, vol. 8, no. 4, pp. 345–350, 2007. View at Publisher · View at Google Scholar · View at PubMed
  71. G. L. Warner, J. W. Ludlow, D. A. Nelson, A. Gaur, and D. W. Scott, “Anti-immunoglobulin treatment of murine B-cell lymphomas induces active transforming growth factor beta but pRB hypophosphorylation is transforming growth factor beta independent,” Cell Growth & Differentiation, vol. 3, no. 3, pp. 175–181, 1992. View at Google Scholar
  72. N. H. Ruddle, “Lymphoid neo-organogenesis: lymphotoxin's role in inflammation and development,” Immunologic Research, vol. 19, no. 2-3, pp. 119–125, 1999. View at Google Scholar
  73. K. Pfeffer, “Biological functions of tumor necrosis factor cytokines and their receptors,” Cytokine & Growth Factor Reviews, vol. 14, no. 3-4, pp. 185–191, 2003. View at Google Scholar
  74. M. Apostolaki, M. Armaka, P. Victoratos, and G. Kollias, “Cellular mechanisms of TNF function in models of inflammation and autoimmunity,” Current Directions in Autoimmunity, vol. 11, pp. 1–26, 2010. View at Publisher · View at Google Scholar · View at PubMed
  75. G. Kollias, E. Douni, G. Kassiotis, and D. Kontoyiannis, “On the role of tumor necrosis factor and receptors in models of multiorgan failure, rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease,” Immunological Reviews, vol. 169, pp. 175–194, 1999. View at Publisher · View at Google Scholar
  76. P. Scheurich, B. Thoma, U. Ucer, and K. Pfizenmaier, “Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-α: induction of TNF receptors on human T cells and TNF-α-mediated enhancement of T cell responses,” Journal of Immunology, vol. 138, no. 6, pp. 1786–1790, 1987. View at Google Scholar
  77. C. T. Harp, S. Ireland, L. S. Davis et al., “Memory B cells from a subset of treatment-naive relapsing-remitting multiple sclerosis patients elicit CD4(+) T-cell proliferation and IFN-gamma production in response to myelin basic protein and myelin oligodendrocyte glycoprotein,” European Journal of Immunology, vol. 40, no. 10, pp. 2942–2956, 2010. View at Google Scholar
  78. G. Trinchieri, “Interleukin-12: a cytokine produced by antigen-presenting cells with immunoregulatory functions in the generation of T-helper cells type 1 and cytotoxic lymphocytes,” Blood, vol. 84, no. 12, pp. 4008–4027, 1994. View at Google Scholar
  79. M. Romano, M. Sironi, C. Toniatti et al., “Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment,” Immunity, vol. 6, no. 3, pp. 315–325, 1997. View at Publisher · View at Google Scholar
  80. J. Van Snick, “Interleukin-6: an overview,” Annual Review of Immunology, vol. 8, pp. 253–278, 1990. View at Google Scholar
  81. A. Kimura and T. Kishimoto, “IL-6: regulator of Treg/Th17 balance,” European Journal of Immunology, vol. 40, no. 7, pp. 1830–1835, 2010. View at Publisher · View at Google Scholar · View at PubMed
  82. T. Hirano, S. Akira, T. Taga, and T. Kishimoto, “Biological and clinical aspects of interleukin 6,” Immunology Today, vol. 11, no. 12, pp. 443–449, 1990. View at Google Scholar
  83. A. Billiau and P. Matthys, “Interferon-γ: a historical perspective,” Cytokine and Growth Factor Reviews, vol. 20, no. 2, pp. 97–113, 2009. View at Publisher · View at Google Scholar · View at PubMed
  84. A. O'Garra, L. Steinman, and K. Gijbels, “CD4+ T-cell subsets in autoimmunity,” Current Opinion in Immunology, vol. 9, no. 6, pp. 872–883, 1997. View at Publisher · View at Google Scholar
  85. M. A. Dayton, T. J. Knobloch, and D. Benjamin, “Human B cell lines express the interferon gamma gene,” Cytokine, vol. 4, no. 6, pp. 454–460, 1992. View at Google Scholar
  86. Y. Pang, Y. Norihisa, D. Benjamin, R. R. S. Kantor, and H. A. Young, “Interferon-γ gene expression in human B-cell lines: induction by interleukin-2, protein kinase C activators, and possible effect of hypomethylation on gene regulation,” Blood, vol. 80, no. 3, pp. 724–732, 1992. View at Google Scholar
  87. A. N. Theofilopoulos, R. Baccala, B. Beutler, and D. H. Kono, “Type I interferons (α/β) in immunity and autoimmunity,” Annual Review of Immunology, vol. 23, pp. 307–336, 2005. View at Publisher · View at Google Scholar · View at PubMed
  88. W. P. Arend, “The balance between IL-1 and IL-1Ra in disease,” Cytokine and Growth Factor Reviews, vol. 13, no. 4-5, pp. 323–340, 2002. View at Publisher · View at Google Scholar
  89. A. Fontana, H. Hengartner, and E. Weber, “Interleukin 1 activity in the synovial fluid of patients with rheumatoid arthritis,” Rheumatology International, vol. 2, no. 2, pp. 49–53, 1982. View at Google Scholar
  90. K. L. Isaacs, R. B. Sartor, and S. Haskill, “Cytokine messenger RNA profiles in inflammatory bowel disease mucosa detected by polymerase chain reaction amplification,” Gastroenterology, vol. 103, no. 5, pp. 1587–1595, 1992. View at Google Scholar
  91. J. A. Hanten, J. P. Vasilakos, C. L. Riter et al., “Comparison of human B cell activation by TLR7 and TLR9 agonists,” BMC Immunology, vol. 9, article 39, 2008. View at Publisher · View at Google Scholar · View at PubMed
  92. S. M. Anderton and S. Fillatreau, “Activated B cells in autoimmune diseases: the case for a regulatory role,” Nature Clinical Practice Rheumatology, vol. 4, no. 12, pp. 657–666, 2008. View at Publisher · View at Google Scholar · View at PubMed
  93. S. Fillatreau, C. H. Sweenie, M. J. McGeachy, D. Gray, and S. M. Anderton, “B cells regulate autoimmunity by provision of IL-10,” Nature Immunology, vol. 3, no. 10, pp. 944–950, 2002. View at Publisher · View at Google Scholar · View at PubMed
  94. M. K. Mann, K. Maresz, L. P. Shriver, Y. Tan, and B. N. Dittel, “B cell regulation of CD4+CD25+ T regulatory cells and IL-10 via B7 is essential for recovery from experimental autoimmune encephalomyelitis,” Journal of Immunology, vol. 178, no. 6, pp. 3447–3456, 2007. View at Google Scholar
  95. J. Correale, M. Farez, and G. Razzitte, “Helminth infections associated with multiple sclerosis induce regulatory B cells,” Annals of Neurology, vol. 64, no. 2, pp. 187–199, 2008. View at Publisher · View at Google Scholar · View at PubMed
  96. M. Duddy, M. Niino, F. Adatia et al., “Distinct effector cytokine profiles of memory and naive human B cell subsets and implication in multiple sclerosis,” Journal of Immunology, vol. 178, no. 10, pp. 6092–6099, 2007. View at Google Scholar
  97. D. P. D'Cruz, S. Mellor-Pita, B. Joven et al., “Transverse myelitis as the first manifestation of systemic lupus erythematosus or lupus-like disease: good functional outcome and relevance of antiphospholipid antibodies,” Journal of Rheumatology, vol. 31, no. 2, pp. 280–285, 2004. View at Google Scholar
  98. Y. U. J. Heo, Y. B. Joo, H. J. Oh et al., “IL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population of rheumatoid arthritis patients,” Immunology Letters, vol. 127, no. 2, pp. 150–156, 2010. View at Publisher · View at Google Scholar · View at PubMed
  99. C. F. Ware, T. L. VanArsdale, P. D. Crowe, and J. L. Browning, “The ligands and receptors of the lymphotoxin system,” Current Topics in Microbiology and Immunology, vol. 198, pp. 175–218, 1995. View at Google Scholar
  100. R. M. Locksley, N. Killeen, and M. J. Lenardo, “The TNF and TNF receptor superfamilies: integrating mammalian biology,” Cell, vol. 104, no. 4, pp. 487–501, 2001. View at Publisher · View at Google Scholar
  101. Y. X. Fu, H. Molina, M. Matsumoto, G. Huang, J. Min, and D. D. Chaplin, “Lymphotoxin-α (LTα) supports development of splenic follicular structure that is required for IgG responses,” Journal of Experimental Medicine, vol. 185, no. 12, pp. 2111–2120, 1997. View at Publisher · View at Google Scholar
  102. P. Yu, Y. Wang, R. K. Chin et al., “B cells control the migration of a subset of dendritic cells into B cell follicles via CXC chemokine ligand 13 in a lymphotoxin-dependent fashion,” Journal of Immunology, vol. 168, no. 10, pp. 5117–5123, 2002. View at Google Scholar
  103. Y. X. Fu, G. Huang, Y. Wang, and D. D. Chaplin, “Lymphotoxin-α-dependent spleen microenvironment supports the generation of memory B cells and is required for their subsequent antigen-induced activation,” Journal of Immunology, vol. 164, no. 5, pp. 2508–2514, 2000. View at Google Scholar
  104. Y. X. Fu, G. Huang, Y. Wang, and D. D. Chaplin, “B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin α-dependent fashion,” Journal of Experimental Medicine, vol. 187, no. 7, pp. 1009–1018, 1998. View at Publisher · View at Google Scholar
  105. C. F. Ware, P. D. Crowe, T. L. Vanarsdale et al., “Tumor necrosis factor (TNF) receptor expression in T lymphocytes: differential regulation of the type I TNF receptor during activation of resting and effector T cells,” Journal of Immunology, vol. 147, no. 12, pp. 4229–4238, 1991. View at Google Scholar
  106. S. R. Plant, H. A. Aknett, and J. P. Y. Ting, “Astroglial-derived lymphotoxin-α exacerbates inflammation and demyelination, but not remyelination,” Glia, vol. 49, no. 1, pp. 1–14, 2005. View at Publisher · View at Google Scholar · View at PubMed
  107. A. Bar-Or, L. Fawaz, B. Fan et al., “Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS?” Annals of Neurology, vol. 67, no. 4, pp. 452–461, 2010. View at Publisher · View at Google Scholar · View at PubMed
  108. V. Pistoia, “Production of cytokines by human B cells in health and disease,” Immunology Today, vol. 18, no. 7, pp. 343–350, 1997. View at Publisher · View at Google Scholar
  109. C. T. Weaver, L. E. Harrington, P. R. Mangan, M. Gavrieli, and K. M. Murphy, “Th17: an effector CD4 T cell lineage with regulatory T cell ties,” Immunity, vol. 24, no. 6, pp. 677–688, 2006. View at Publisher · View at Google Scholar · View at PubMed
  110. K. Kikly, L. Liu, S. Na, and J. D. Sedgwick, “The IL-23/Th axis: therapeutic targets for autoimmune inflammation,” Current Opinion in Immunology, vol. 18, no. 6, pp. 670–675, 2006. View at Publisher · View at Google Scholar · View at PubMed
  111. M. J. McGeachy, K. S. Bak-Jensen, Y. I. Chen et al., “TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T-17 cell-mediated pathology,” Nature Immunology, vol. 8, no. 12, pp. 1390–1397, 2007. View at Publisher · View at Google Scholar · View at PubMed
  112. E. Bettelli, Y. Carrier, W. Gao et al., “Reciprocal developmental pathways for the generation of pathogenic effector T17 and regulatory T cells,” Nature, vol. 441, no. 7090, pp. 235–238, 2006. View at Publisher · View at Google Scholar · View at PubMed
  113. M. Veldhoen, R. J. Hocking, C. J. Atkins, R. M. Locksley, and B. Stockinger, “TGFβ in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells,” Immunity, vol. 24, no. 2, pp. 179–189, 2006. View at Publisher · View at Google Scholar · View at PubMed
  114. A. Jäger, V. Dardalhon, R. A. Sobel, E. Bettelli, and V. K. Kuchroo, “Th1, Th17, and Th9 effector cells induce experimental autoimmune encephalomyelitis with different pathological phenotypes,” Journal of Immunology, vol. 183, no. 11, pp. 7169–7177, 2009. View at Publisher · View at Google Scholar · View at PubMed
  115. M. K. Racke, B. Cannella, P. Albert, M. Sporn, C. S. Raine, and D. E. McFarlin, “Evidence of endogenous regulatory function of transforming growth factor-β1 in experimental allergic encephalomyelitis,” International Immunology, vol. 4, no. 5, pp. 615–620, 1992. View at Google Scholar
  116. P. A. Calabresi, N. S. Fields, H. W. Maloni et al., “Phase 1 trial of transforming growth factor beta 2 in chronic progressive MS,” Neurology, vol. 51, no. 1, pp. 289–292, 1998. View at Google Scholar
  117. J. Link, B. He, V. Navikas et al., “Transforming growth factor-β1 suppresses autoantigen-induced expression of pro-inflammatory cytokines but not of interleukin-10 in multiple sclerosis and myasthenia gravis,” Journal of Neuroimmunology, vol. 58, no. 1, pp. 21–35, 1995. View at Publisher · View at Google Scholar
  118. A. Uzawa, M. Mori, M. Ito et al., “Markedly increased CSF interleukin-6 levels in neuromyelitis optica, but not in multiple sclerosis,” Journal of Neurology, vol. 256, no. 12, pp. 2082–2084, 2009. View at Publisher · View at Google Scholar · View at PubMed
  119. A. I. Kaplin, D. M. Deshpande, E. Scott et al., “IL-6 induces regionally selective spinal cord injury in patients with the neuroinflammatory disorder transverse myelitis,” Journal of Clinical Investigation, vol. 115, no. 10, pp. 2731–2741, 2005. View at Publisher · View at Google Scholar · View at PubMed
  120. C. Lock, G. Hermans, R. Pedotti et al., “Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis,” Nature Medicine, vol. 8, no. 5, pp. 500–508, 2002. View at Publisher · View at Google Scholar · View at PubMed
  121. D. Maimone, S. Gregory, B. G. W. Arnason, and A. T. Reder, “Cytokine levels in the cerebrospinal fluid and serum of patients with multiple sclerosis,” Journal of Neuroimmunology, vol. 32, no. 1, pp. 67–74, 1991. View at Publisher · View at Google Scholar
  122. S. L. Hauser, T. H. Doolittle, R. Lincoln, R. H. Brown, and C. A. Dinarello, “Cytokine accumulations in CSF of multiple sclerosis patients: frequent detection of interleukin-1 and tumor necrosis factor but not interleukin-6,” Neurology, vol. 40, no. 11, pp. 1735–1739, 1990. View at Google Scholar
  123. M. A. Laurenzi, A. Siden, M. A. A. Persson, G. Norkrans, L. Hagberg, and F. Chiodi, “Cerebrospinal fluid interleukin-6 activity in HIV infection and inflammatory and noninflammatory diseases of the nervous system,” Clinical Immunology and Immunopathology, vol. 57, no. 2, pp. 233–241, 1990. View at Publisher · View at Google Scholar
  124. R. K. Benwell and D. R. Lee, “Essential and synergistic roles of IL1 and IL6 in human Th17 differentiation directed by TLR ligand-activated dendritic cells,” Clinical Immunology, vol. 134, no. 2, pp. 178–187, 2010. View at Publisher · View at Google Scholar · View at PubMed
  125. H. W. Lim, J. Lee, P. Hillsamer, and C. H. Kim, “Human Th17 cells share major trafficking receptors with both polarized effector T cells and FOXP3+ regulatory T cells,” Journal of Immunology, vol. 180, no. 1, pp. 122–129, 2008. View at Google Scholar
  126. Y. Nakatsuji, M. Nakano, M. Moriya et al., “Beneficial effect of interferon-β treatment in patients with multiple sclerosis is associated with transient increase in serum IL-6 level in response to interferon-β injection,” Cytokine, vol. 36, no. 1-2, pp. 69–74, 2006. View at Publisher · View at Google Scholar · View at PubMed
  127. J. M. R. Frade, M. Mellado, G. Del Real, J. C. Gutierrez-Ramos, P. Lind, and C. Martinez-A. C., “Characterization of the CCR2 chemokine receptor: functional CCR2 receptor expression in B cells,” Journal of Immunology, vol. 159, no. 11, pp. 5576–5584, 1997. View at Google Scholar
  128. K. A. Dzenko, A. V. Andjelkovic, W. A. Kuziel, and J. S. Pachter, “The chemokine receptor CCR2 mediates the binding and internalization of monocyte chemoattractant protein-1 along brain microvessels,” Journal of Neuroscience, vol. 21, no. 23, pp. 9214–9223, 2001. View at Google Scholar
  129. H. Nakajima, M. Sugino, F. Kimura et al., “Increased intrathecal chemokine receptor CCR2 expression in multiple sclerosis,” Biomark Insights, vol. 2, pp. 463–468, 2007. View at Google Scholar
  130. J. W. Morgan, N. Kouttab, D. Ford, and A. L. Maizel, “Vitamin D-mediated gene regulation in phenotypically defined human B cell subpopulations,” Endocrinology, vol. 141, no. 9, pp. 3225–3234, 2000. View at Publisher · View at Google Scholar
  131. S. Chen, G. P. Sims, X. C. Xiao, Y. G. Yue, S. Chen, and P. E. Lipsky, “Modulatory effects of 1,25-dihydroxyvitamin D on human B cell differentiation,” Journal of Immunology, vol. 179, no. 3, pp. 1634–1647, 2007. View at Google Scholar
  132. O. Neuhaus, C. Farina, A. Yassouridis et al., “Multiple sclerosis: comparison of copolymer-1-reactive T cell lines from treated and untreated subjects reveals cytokine shift from T helper 1 to T helper 2 cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 13, pp. 7452–7457, 2000. View at Publisher · View at Google Scholar
  133. M. Niino, M. Hirotani, Y. Miyazaki, and H. Sasaki, “Memory and naïve B-cell subsets in patients with multiple sclerosis,” Neuroscience Letters, vol. 464, no. 1, pp. 74–78, 2009. View at Publisher · View at Google Scholar · View at PubMed
  134. C. J. Hedegaard, M. Krakauer, K. Bendtzen, P. S. Sørensen, F. Sellebjerg, and C. H. Nielsen, “The effect of β-interferon therapy on myelin basic protein-elicited CD4+ T cell proliferation and cytokine production in multiple sclerosis,” Clinical Immunology, vol. 129, no. 1, pp. 80–89, 2008. View at Publisher · View at Google Scholar · View at PubMed
  135. G. P. Christophi, M. Panos, C. A. Hudson et al., “Interferon-β treatment in multiple sclerosis attenuates inflammatory gene expression through inducible activity of the phosphatase SHP-1,” Clinical Immunology, vol. 133, no. 1, pp. 27–44, 2009. View at Publisher · View at Google Scholar · View at PubMed