Table of Contents Author Guidelines Submit a Manuscript
Corrigendum

A corrigendum for this article has been published. To view the corrigendum, please click here.

Journal of Immunology Research
Volume 2015, Article ID 348746, 11 pages
http://dx.doi.org/10.1155/2015/348746
Review Article

The Story of CD4+CD28 T Cells Revisited: Solved or Still Ongoing?

Clinic VI, Laboratory of Molecular Biology and Rheumatology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria

Received 29 November 2014; Revised 10 February 2015; Accepted 19 February 2015

Academic Editor: Peirong Jiao

Copyright © 2015 Kathrin Maly and Michael Schirmer. 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. D. Schmidt, J. J. Goronzy, and C. M. Weyand, “CD4+ CD7- CD28- T cells are expanded in rheumatoid arthritis and are characterized by autoreactivity,” The Journal of Clinical Investigation, vol. 97, no. 9, pp. 2027–2037, 1996. View at Publisher · View at Google Scholar · View at Scopus
  2. D. Schmidt, P. B. Martens, C. M. Weyand, and J. J. Goronzy, “The repertoire of CD4+ CD28-T cells in rheumatoid arthritis,” Molecular Medicine, vol. 2, no. 5, pp. 608–618, 1996. View at Google Scholar · View at Scopus
  3. K. J. Warrington, A. N. Vallejo, C. M. Weyand, and J. J. Goronzy, “CD28 loss in senescent CD4+ T cells: reversal by interleukin-12 stimulation,” Blood, vol. 101, no. 9, pp. 3543–3549, 2003. View at Publisher · View at Google Scholar · View at Scopus
  4. A. N. Vallejo, J. C. Brandes, C. M. Weyand, and J. J. Goronzy, “Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence,” The Journal of Immunology, vol. 162, no. 11, pp. 6572–6579, 1999. View at Google Scholar · View at Scopus
  5. A. N. Vallejo, A. R. Nestel, M. Schirmer, C. M. Weyand, and J. J. Goronzy, “Aging-related deficiency of CD28 expression in CD4+ T cells is associated with the loss of gene-specific nuclear factor binding activity,” The Journal of Biological Chemistry, vol. 273, no. 14, pp. 8119–8129, 1998. View at Publisher · View at Google Scholar · View at Scopus
  6. A. N. Vallejo, E. Bryl, K. Klarskov, S. Naylor, C. M. Weyand, and J. J. Goronzy, “Molecular basis for the loss of CD28 expression in senescent T cells,” The Journal of Biological Chemistry, vol. 277, no. 49, pp. 46940–46949, 2002. View at Publisher · View at Google Scholar · View at Scopus
  7. R. Javahery, A. Khachi, K. Lo, B. Zenzie-Gregory, and S. T. Smale, “DNA sequence requirements for transcriptional initiator activity in mammalian cells,” Molecular and Cellular Biology, vol. 14, no. 1, pp. 116–127, 1994. View at Google Scholar · View at Scopus
  8. A. E. R. Fasth, D. Cao, R. van Vollenhoven, C. Trollmo, and V. Malmström, “CD28nullCD4+T cells—characterization of an effector memory T-cell population in patients with rheumatoid arthritis,” Scandinavian Journal of Immunology, vol. 60, no. 1, pp. 199–208, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. C. Duftner, C. Dejaco, W. Kullich et al., “Preferential type 1 chemokine receptors and cytokine production of CD28- T cells in ankylosing spondylitis,” Annals of the Rheumatic Diseases, vol. 65, no. 5, pp. 647–653, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. E. Bryl, A. N. Vallejo, C. M. Weyand, and J. J. Goronzy, “Down-regulation of CD28 expression by TNF-α,” The Journal of Immunology, vol. 167, no. 6, pp. 3231–3238, 2001. View at Publisher · View at Google Scholar · View at Scopus
  11. E. Bryl, A. N. Vallejo, E. L. Matteson, J. M. Witkowski, C. M. Weyand, and J. J. Goronzy, “Modulation of CD28 expression with anti-tumor necrosis factor α therapy in rheumatoid arthritis,” Arthritis and Rheumatism, vol. 52, no. 10, pp. 2996–3003, 2005. View at Publisher · View at Google Scholar · View at Scopus
  12. V. Rizzello, G. Liuzzo, S. Brugaletta, A. Rebuzzi, L. M. Biasucci, and F. Crea, “Modulation of CD4+CD28null T lymphocytes by tumor necrosis factor-α blockade in patients with unstable angina,” Circulation, vol. 113, no. 19, pp. 2272–2277, 2006. View at Publisher · View at Google Scholar · View at Scopus
  13. J. J. Goronzy, J. W. Fulbright, C. S. Crowson, G. A. Poland, W. M. O'Fallon, and C. M. Weyand, “Value of immunological markers in predicting responsiveness to influenza vaccination in elderly individuals,” Journal of Virology, vol. 75, no. 24, pp. 12182–12187, 2001. View at Publisher · View at Google Scholar · View at Scopus
  14. Y. O. S. H. Morishita, H. Sao, J. A. Hansen, and P. J. Martin, “A distinct subset of human CD4+ cells with a limited alloreactive T cell receptor repertoire,” The Journal of Immunology, vol. 143, no. 9, pp. 2783–2789, 1989. View at Google Scholar · View at Scopus
  15. C. Dejaco, C. Duftner, A. Klauser, and M. Schirmer, “Altered T-cell subtypes in spondyloarthritis, rheumatoid arthritis and polymyalgia rheumatica,” Rheumatology International, vol. 30, no. 3, pp. 297–303, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. M. Schirmer, A. N. Vallejo, C. M. Weyand, and J. J. Goronzy, “Resistance to apoptosis and elevated expression of bcl-2 in clonally expanded CD4+CD28-T cells from rheumatoid arthritis patients,” Journal of Immunology, vol. 161, no. 2, pp. 1018–1025, 1998. View at Google Scholar · View at Scopus
  17. C. Duftner, C. Goldberger, A. Falkenbach et al., “Prevalence, clinical relevance and characterization of circulating cytotoxic CD4+CD28T cells in ankylosing spondylitis.,” Arthritis Research & Therapy, vol. 5, no. 5, pp. R292–R300, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. A. E. R. Fasth, M. Dastmalchi, A. Rahbar et al., “T cell infiltrates in the muscles of patients with dermatomyositis and polymyositis are dominated by CD28null T cells,” The Journal of Immunology, vol. 183, no. 7, pp. 4792–4799, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. C. Dejaco, C. Duftner, J. Al-Massad et al., “NKG2D stimulated T-cell autoreactivity in giant cell arteritis and polymyalgia rheumatica,” Annals of the Rheumatic Diseases, vol. 72, no. 11, pp. 1852–1859, 2013. View at Publisher · View at Google Scholar · View at Scopus
  20. I. E. Dumitriu, E. T. Araguás, C. Baboonian, and J. C. Kaski, “CD4+CD28null T cells in coronary artery disease: when helpers become killers,” Cardiovascular Research, vol. 81, no. 1, pp. 11–19, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. P. Lamprecht, F. Moosig, E. Csernok et al., “CD28 negative T cells are enriched in granulomatous lesions of the respiratory tract in Wegener's granulomatosis,” Thorax, vol. 56, no. 10, pp. 751–757, 2001. View at Publisher · View at Google Scholar · View at Scopus
  22. M. J. Pinto-Medel, J. A. García-León, B. Oliver-Martos et al., “The CD4+ T-cell subset lacking expression of the CD28 costimulatory molecule is expanded and shows a higher activation state in multiple sclerosis,” Journal of Neuroimmunology, vol. 243, no. 1-2, pp. 1–11, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. J. García de Tena, L. Manzano, J. C. Leal, E. San Antonio, V. Sualdea, and M. Álvarez-Mon, “Active Crohn's disease patients show a distinctive expansion of circulating memory CD4+CD45RO+CD28null T cells,” Journal of Clinical Immunology, vol. 24, no. 2, pp. 185–196, 2004. View at Publisher · View at Google Scholar · View at Scopus
  24. G. Liuzzo, S. L. Kopecky, R. L. Frye et al., “Perturbation of the T-cell repertoire in patients with unstable angina,” Circulation, vol. 100, no. 21, pp. 2135–2139, 1999. View at Publisher · View at Google Scholar · View at Scopus
  25. H. F. Alber, C. Duftner, M. Wanitschek et al., “Neopterin, CD4+CD28—lymphocytes and the extent and severity of coronary artery disease,” International Journal of Cardiology, vol. 135, no. 1, pp. 27–35, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. G. Liuzzo, J. J. Goronzy, H. Yang et al., “Monoclonal T-cell proliferation and plaque instability in acute coronary syndromes,” Circulation, vol. 101, no. 25, pp. 2883–2888, 2000. View at Publisher · View at Google Scholar · View at Scopus
  27. C. Duftner, R. Seiler, P. Klein-Weigel et al., “High prevalence of circulating CD4+CD28- T-cells in patients with small abdominal aortic aneurysms,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 7, pp. 1347–1352, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Pawlik, M. Florczak, M. Masiuk et al., “The expansion of CD4+CD28—T cells in patients with chronic kidney graft rejection,” Transplantation Proceedings, vol. 35, no. 8, pp. 2902–2904, 2003. View at Google Scholar · View at Scopus
  29. E. M. M. van Leeuwen, E. B. M. Remmerswaal, M. T. M. Vossen et al., “Emergence of a CD4+CD28 granzyme B+, cytomegalovirus-specific T cell subset after recovery of primary cytomegalovirus infection,” Journal of Immunology, vol. 173, no. 3, pp. 1834–1841, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. J. van Bergen, E. M. C. Kooy-Winkelaar, H. van Dongen et al., “Functional killer Ig-like receptors on human memory CD4+ T cells specific for cytomegalovirus,” The Journal of Immunology, vol. 182, no. 7, pp. 4175–4182, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. O. K. Haffar, M. D. Smithgall, J. G. P. Wong, J. Bradshaw, and P. S. Linsley, “Human immunodeficiency virus type 1 infection of CD4+ T cells down-regulates the expression of CD28: effect on T cell activation and cytokine production,” Clinical Immunology and Immunopathology, vol. 77, no. 3, pp. 262–270, 1995. View at Publisher · View at Google Scholar · View at Scopus
  32. R. Kämmerer, A. Iten, P. C. Frei, and P. Bürgisser, “Expansion of T cells negative for CD28 expression in HIV infection. Relation to activation markers and cell adhesion molecules, and correlation with prognostic markers,” Medical Microbiology and Immunology, vol. 185, no. 1, pp. 19–25, 1996. View at Publisher · View at Google Scholar · View at Scopus
  33. C. A. S. Menezes, M. O. C. Rocha, P. E. A. Souza, A. C. L. Chaves, K. J. Gollob, and W. O. Dutra, “Phenotypic and functional characteristics of CD28+ and CD28 cells from chagasic patients: distinct repertoire and cytokine expression,” Clinical & Experimental Immunology, vol. 137, no. 1, pp. 129–138, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. Y. Wang, J. Bai, F. Li et al., “Characteristics of expanded CD4+CD28null T cells in patients with chronic hepatitis B,” Immunological Investigations, vol. 38, no. 5, pp. 434–446, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. B. Broux, S. Markovic-Plese, P. Stinissen, and N. Hellings, “Pathogenic features of CD4+CD28- T cells in immune disorders,” Trends in Molecular Medicine, vol. 18, no. 8, pp. 446–453, 2012. View at Publisher · View at Google Scholar · View at Scopus
  36. A. N. Vallejo, C. M. Weyand, and J. J. Goronzy, “T-cell senescence: a culprit of immune abnormalities in chronic inflammation and persistent infection,” Trends in Molecular Medicine, vol. 10, no. 3, pp. 119–124, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. U. Wagner, M. Pierer, S. Kaltenhäuser et al., “Clonally expanded CD4+CD28null T cells in rheumatoid arthritis use distinct combinations of T cell receptor BV and BJ elements,” European Journal of Immunology, vol. 33, no. 1, pp. 79–84, 2003. View at Publisher · View at Google Scholar · View at Scopus
  38. M. López-Botet, A. Muntasell, and C. Vilches, “The CD94/NKG2C+ NK-cell subset on the edge of innate and adaptive immunity to human cytomegalovirus infection,” Seminars in Immunology, vol. 26, no. 2, pp. 145–151, 2014. View at Publisher · View at Google Scholar · View at Scopus
  39. J. Olsson, A. Wikby, B. Johansson, S. Löfgren, B. O. Nilsson, and F. G. Ferguson, “Age-related change in peripheral blood T-lymphocyte subpopulations and cytomegalovirus infection in the very old: the Swedish Longitudinal OCTO Immune Study,” Mechanisms of Ageing and Development, vol. 121, no. 1–3, pp. 187–201, 2001. View at Publisher · View at Google Scholar · View at Scopus
  40. J. M. Fletcher, M. Vukmanovic-Stejic, P. J. Dunne et al., “Cytomegalovirus-specific CD4+ T cells in healthy carriers are continuously driven to replicative exhaustion,” Journal of Immunology, vol. 175, no. 12, pp. 8218–8225, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. C. Söderberg-Nauclér, “HCMV microinfections in inflammatory diseases and cancer,” Journal of Clinical Virology, vol. 41, no. 3, pp. 218–223, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Hooper, E. G. Kallas, D. Coffin, D. Campbell, T. G. Evans, and R. J. Looney, “Cytomegalovirus seropositivity is associated with the expansion of CD4+CD28 and CD8+CD28 T cells in rheumatoid arthritis,” The Journal of Rheumatology, vol. 26, no. 7, pp. 1452–1457, 1999. View at Google Scholar · View at Scopus
  43. B. Zal, J. C. Kaski, G. Arno et al., “Heat-shock protein 60-reactive CD4+CD28null T cells in patients with acute coronary syndromes,” Circulation, vol. 109, no. 10, pp. 1230–1235, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. W. van Eden, R. van der Zee, and B. Prakken, “Heat-shock proteins induce T-cell regulation of chronic inflammation,” Nature Reviews Immunology, vol. 5, no. 4, pp. 318–330, 2005. View at Publisher · View at Google Scholar · View at Scopus
  45. B. Zal, J. C. Kaski, J. P. Akiyu et al., “Differential pathways govern CD4+CD28 T cell proinflammatory and effector responses in patients with coronary artery disease,” The Journal of Immunology, vol. 181, no. 8, pp. 5233–5241, 2008. View at Publisher · View at Google Scholar · View at Scopus
  46. J. H. Yen, B. E. Moore, T. Nakajima et al., “Major histocompatibility complex class I-recognizing receptors are disease risk genes in rheumatoid arthritis,” The Journal of Experimental Medicine, vol. 193, no. 10, pp. 1159–1167, 2001. View at Publisher · View at Google Scholar · View at Scopus
  47. L. Hayflick and P. S. Moorhead, “The serial cultivation of human diploid cell strains,” Experimental Cell Research, vol. 25, no. 3, pp. 585–621, 1961. View at Publisher · View at Google Scholar · View at Scopus
  48. H. F. Valenzuela and R. B. Effros, “Divergent telomerase and CD28 expression patterns in human CD4 and CD8 T cells following repeated encounters with the same antigenic stimulus,” Clinical Immunology, vol. 105, no. 2, pp. 117–125, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. R. B. Effros and G. Pawelec, “Replicative senescence of T cells: does the Hayflick Limit lead to immune exhaustion?” Immunology Today, vol. 18, no. 9, pp. 450–454, 1997. View at Publisher · View at Google Scholar · View at Scopus
  50. C. M. Counter, A. A. Avilion, C. E. LeFeuvre et al., “Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity,” The EMBO Journal, vol. 11, no. 5, pp. 1921–1929, 1992. View at Google Scholar · View at Scopus
  51. K. Koetz, E. Bryl, K. Spickschen, W. M. O'Fallon, J. J. Goronzy, and C. M. Weyand, “T cell homeostasis in patients with rheumatoid arthritis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 16, pp. 9203–9208, 2000. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Fessler, A. Raicht, R. Husic et al., “Premature senescence of T-cell subsets in axial spondyloarthritis,” Annals of the Rheumatic Diseases, 2015. View at Publisher · View at Google Scholar
  53. F. A. Harding, J. G. McArthur, J. A. Gross, D. H. Raulet, and J. P. Allison, “CD28-mediated signalling co-stimulates murine T cells and prevents induction of anergy in T-cell clones,” Nature, vol. 356, no. 6370, pp. 607–609, 1992. View at Publisher · View at Google Scholar · View at Scopus
  54. W. Park, C. M. Weyand, D. Schmidt, and J. J. Goronzy, “Co-stimulatory pathways controlling activation and peripheral tolerance of human CD4+CD28 cells,” European Journal of Immunology, vol. 27, no. 5, pp. 1082–1090, 1997. View at Publisher · View at Google Scholar · View at Scopus
  55. A. N. Vallejo, M. Schirmer, C. M. Weyand, and J. J. Goronzy, “Clonality and longevity of CD4+CD28null T cells are associated with defects in apoptotic pathways,” Journal of Immunology, vol. 165, no. 11, pp. 6301–6307, 2000. View at Publisher · View at Google Scholar · View at Scopus
  56. P. H. Krammer, “CD95(APO-1/Fas)-mediated apoptosis: live and let die,” Advances in Immunology, vol. 71, pp. 163–210, 1999. View at Google Scholar · View at Scopus
  57. T. Kataoka, M. Schröter, M. Hahne et al., “FLIP prevents apoptosis induced by death receptors but not by perforin/granzyme B, chemotherapeutic drugs, and gamma irradiation,” The Journal of Immunology, vol. 161, no. 8, pp. 3936–3942, 1998. View at Google Scholar · View at Scopus
  58. C. M. Weyand, J. C. Brandes, D. Schmidt, J. W. Fulbright, and J. J. Goronzy, “Functional properties of CD4+CD28 T cells in the aging immune system,” Mechanisms of Ageing and Development, vol. 102, no. 2-3, pp. 131–147, 1998. View at Publisher · View at Google Scholar · View at Scopus
  59. T. Namekawa, U. G. Wagner, J. J. Goronzy, and C. M. Weyand, “Functional subsets of CD4 T cells in rheumatoid synovitis,” Arthritis & Rheumatism, vol. 41, no. 12, pp. 2108–2116, 1998. View at Publisher · View at Google Scholar
  60. D. D. Yang, D. Conze, A. J. Whitmarsh et al., “Differentiation of CD4+ T cells to Th1 cells requires MAP kinase JNK2,” Immunity, vol. 9, no. 4, pp. 575–585, 1998. View at Publisher · View at Google Scholar · View at Scopus
  61. I. E. Dumitriu, P. Baruah, C. J. Finlayson et al., “High levels of costimulatory receptors OX40 and 4-1BB characterize CD4+CD28null T cells in patients with acute coronary syndrome,” Circulation Research, vol. 110, no. 6, pp. 857–869, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. T. Nakajima, S. Schulte;, K. J. Warrington et al., “T-cell-mediated lysis of endothelial cells in acute coronary syndromes,” Circulation, vol. 105, no. 5, pp. 570–575, 2002. View at Publisher · View at Google Scholar · View at Scopus
  63. E. Liaskou, L. E. Jeffery, P. J. Trivedi et al., “Loss of CD28 expression by liver-infiltrating T cells contributes to pathogenesis of primary sclerosing cholangitis,” Gastroenterology, vol. 147, no. 1, pp. 221.e7–232.e7, 2014. View at Publisher · View at Google Scholar
  64. R. Gerli, G. Schillaci, A. Giordano et al., “CD4+CD28- T lymphocytes contribute to early atherosclerotic damage in rheumatoid arthritis patients,” Circulation, vol. 109, no. 22, pp. 2744–2748, 2004. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Pawlik, L. Ostanek, I. Brzosko et al., “Therapy with infliximab decreases the CD4+CD28- T cell compartment in peripheral blood in patients with rheumatoid arthritis,” Rheumatology International, vol. 24, no. 6, pp. 351–354, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. S. Giubilato, G. Liuzzo, S. Brugaletta et al., “Expansion of CD4+CD28null T-lymphocytes in diabetic patients: exploring new pathogenetic mechanisms of increased cardiovascular risk in diabetes mellitus,” European Heart Journal, vol. 32, no. 10, pp. 1214–1226, 2011. View at Publisher · View at Google Scholar · View at Scopus
  67. V. Pasceri, J. T. Willerson, and E. T. H. Yeh, “Direct proinflammatory effect of C-reactive protein on human endothelial cells,” Circulation, vol. 102, no. 18, pp. 2165–2168, 2000. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Pieper, S. Johansson, O. Snir et al., “Peripheral and site-specific CD4+ CD28null T cells from rheumatoid arthritis patients show distinct characteristics,” Scandinavian Journal of Immunology, vol. 79, no. 2, pp. 149–155, 2014. View at Publisher · View at Google Scholar · View at Scopus
  69. A. N. Vallejo, “CD28 extinction in human T cells: altered functions and the program of T-cell senescence,” Immunological Reviews, vol. 205, pp. 158–169, 2005. View at Publisher · View at Google Scholar · View at Scopus
  70. V. Groh, A. Brühl, H. El-Gabalawy, J. L. Nelson, and T. Spies, “Stimulation of T cell autoreactivity by anomalous expression of NKG2D and its MIC ligands in rheumatoid arthritis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 16, pp. 9452–9457, 2003. View at Publisher · View at Google Scholar · View at Scopus
  71. T. Namekawa, M. R. Snyder, J.-H. Yen et al., “Killer cell actuating receptors function as costimulatory molecules on CD4+CD28null T cells clonally expanded in rheumatoid arthritis,” The Journal of Immunology, vol. 165, no. 2, pp. 1138–1145, 2000. View at Publisher · View at Google Scholar · View at Scopus
  72. K. J. Warrington, S. Takemura, J. J. Goronzy, and C. M. Weyand, “CD4+,CD28− T cells in rheumatoid arthritis patients combine features of the innate and adaptive immune systems,” Arthritis & Rheumatism, vol. 44, no. 1, pp. 13–20, 2001. View at Publisher · View at Google Scholar
  73. B. Raffeiner, C. Dejaco, C. Duftner et al., “Between adaptive and innate immunity: TLR4-mediated perforin production by CD28null T-helper cells in ankylosing spondylitis,” Arthritis Research & Therapy, vol. 7, no. 6, pp. R1412–1420, 2005. View at Publisher · View at Google Scholar · View at Scopus
  74. B. Broux, K. Pannemans, X. Zhang et al., “CX3CR1 drives cytotoxic CD4+CD28- T cells into the brain of multiple sclerosis patients,” Journal of Autoimmunity, vol. 38, no. 1, pp. 10–19, 2012. View at Publisher · View at Google Scholar · View at Scopus
  75. F. Facchetti, C. Appiani, L. Salvi, J. Levy, and L. D. Notarangelo, “Immunohistologic analysis of ineffective CD40-CD40 ligand interaction in lymphoid tissues from patients with X-linked immunodeficiency with hyper- IgM: abortive germinal center cell reaction and severe depletion of follicular dendritic cells,” The Journal of Immunology, vol. 154, no. 12, pp. 6624–6633, 1995. View at Google Scholar · View at Scopus
  76. G. Hodge, S. Hodge, J. Ahern, C.-L. Holmes-Liew, P. N. Reynolds, and M. Holmes, “Up-regulation of alternate co-stimulatory molecules on proinflammatory CD28null T cells in bronchiolitis obliterans syndrome,” Clinical & Experimental Immunology, vol. 173, no. 1, pp. 150–160, 2013. View at Publisher · View at Google Scholar · View at Scopus
  77. H. Sawai, Y. W. Park, J. Roberson, T. Imai, J. J. Goronzy, and C. M. Weyand, “T cell costimulation by Fractalkine-Expressing synoviocytes in rheumatoid arthritis,” Arthritis & Rheumatism, vol. 52, no. 5, pp. 1392–1401, 2005. View at Publisher · View at Google Scholar · View at Scopus
  78. R. Yano, M. Yamamura, K. Sunahori et al., “Recruitment of CD16+ monocytes into synovial tissues is mediated by fractalkine and CX3CR1 in rheumatoid arthritis patients,” Acta Medica Okayama, vol. 61, no. 2, pp. 89–98, 2007. View at Google Scholar · View at Scopus
  79. M. V. Volin, J. M. Woods, M. A. Amin, M. A. Connors, L. A. Harlow, and A. E. Koch, “Fractalkine: a novel angiogenic chemokine in rheumatoid arthritis,” The American Journal of Pathology, vol. 159, no. 4, pp. 1521–1530, 2001. View at Publisher · View at Google Scholar · View at Scopus
  80. A. N. Vallejo, L. O. Mügge, P. A. Klimiuk, C. M. Weyand, and J. J. Goronzy, “Central role of thrombospondin-1 in the activation and clonal expansion of inflammatory T cells,” The Journal of Immunology, vol. 164, no. 6, pp. 2947–2954, 2000. View at Publisher · View at Google Scholar · View at Scopus
  81. X. Zhang, T. Nakajima, J. J. Goronzy, and C. M. Weyand, “Tissue trafficking patterns of effector memory CD4+ T cells in rheumatoid arthritis,” Arthritis & Rheumatism, vol. 52, no. 12, pp. 3839–3849, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. C. Duftner, C. Dejaco, and M. Schirmer, “Early aged T-cells in immune-mediated diseases,” Current Immunology Reviews, vol. 7, no. 1, pp. 124–132, 2011. View at Publisher · View at Google Scholar · View at Scopus
  83. M. R. Snyder, C. M. Weyand, and J. J. Goronzy, “The double life of NK receptors: stimulation or co-stimulation?” Trends in Immunology, vol. 25, no. 1, pp. 25–32, 2004. View at Publisher · View at Google Scholar · View at Scopus
  84. S. Bauer, V. Groh, J. Wu et al., “Activation of NK cells and T cells by NKG2D, a receptor for stress—inducible MICA,” Science, vol. 285, no. 5428, pp. 727–729, 1999. View at Publisher · View at Google Scholar · View at Scopus
  85. V. Groh, J. Wu, C. Yee, and T. Spies, “Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation,” Nature, vol. 419, no. 6908, pp. 734–738, 2002. View at Publisher · View at Google Scholar · View at Scopus
  86. G. David, Z. Djaoud, C. Willem et al., “Large spectrum of HLA-C recognition by killer Ig-like receptor (KIR)2DL2 and KIR2DL3 and restricted C1 specificity of KIR2DS2: dominant impact of KIR2DL2/KIR2DS2 on KIR2D NK cell repertoire formation,” Journal of Immunology, vol. 191, no. 9, pp. 4778–4788, 2013. View at Publisher · View at Google Scholar · View at Scopus
  87. B. Zal, N. Chitalia, Y. S. Ng et al., “Killer cell immunoglobulin receptor profile on CD4+ CD28 T cells and their pathogenic role in nondialysis and dialysis dependent chronic kidney disease patients,” Immunology, 2014. View at Publisher · View at Google Scholar
  88. O. Takeuchi and S. Akira, “Pattern recognition receptors and inflammation,” Cell, vol. 140, no. 6, pp. 805–820, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. R. S. Schwartz, M. G. Netea, and J. W. van der Meer, “Immunodeficiency and genetic defects of pattern-recognition receptors,” New England Journal of Medicine, vol. 364, pp. 60–70, 2011. View at Google Scholar
  90. T. Kawai and S. Akira, “TLR signaling,” Cell Death and Differentiation, vol. 13, no. 5, pp. 816–825, 2006. View at Publisher · View at Google Scholar · View at Scopus
  91. S. Sivori, S. Carlomagno, S. Pesce, A. Moretta, M. Vitale, and E. Marcenaro, “TLR/NCR/KIR: Which one to use and when?” Frontiers in Immunology, vol. 5, article 105, 2014. View at Publisher · View at Google Scholar · View at Scopus
  92. M. Croft and C. Dubey, “Accessory molecule and costimulation requirements for CD4 T cell response,” Critical Reviews in Immunology, vol. 17, no. 1, pp. 89–118, 1997. View at Publisher · View at Google Scholar · View at Scopus
  93. M. I. Reinhold, F. P. Lindberg, G. J. Kersh, P. M. Allen, and E. J. Brown, “Costimulation of T cell activation by integrin-associated protein (CD47) is an adhesion-dependent, CD28-independent signaling pathway,” The Journal of Experimental Medicine, vol. 185, no. 1, pp. 1–11, 1997. View at Publisher · View at Google Scholar · View at Scopus
  94. A. N. Vallejo, H. Yang, P. A. Klimiuk, C. M. Weyand, and J. J. Goronzy, “Synoviocyte-mediated expansion of inflammatory T cells in rheumatoid synovitis is dependent on CD47-thrombospondin 1 interaction,” The Journal of Immunology, vol. 171, no. 4, pp. 1732–1740, 2003. View at Publisher · View at Google Scholar · View at Scopus
  95. H. Hoff, K. Knieke, Z. Cabail et al., “Surface CD152 (CTLA-4) expression and signaling dictates longevity of CD28null T cells,” Journal of Immunology, vol. 182, no. 9, pp. 5342–5351, 2009. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Croft, “Costimulation of T cells by OX40, 4-1BB, and CD27,” Cytokine and Growth Factor Reviews, vol. 14, no. 3-4, pp. 265–273, 2003. View at Publisher · View at Google Scholar · View at Scopus
  97. T. So, S. W. Lee, and M. Croft, “Immune regulation and control of regulatory T cells by OX40 and 4-1BB,” Cytokine and Growth Factor Reviews, vol. 19, no. 3-4, pp. 253–262, 2008. View at Publisher · View at Google Scholar · View at Scopus
  98. A. Komocsi, P. Lamprecht, E. Csernok et al., “Peripheral blood and granuloma CD4+CD28 T cells are a major source of interferon-γ and tumor necrosis factor-α in Wegener's granulomatosis,” The American Journal of Pathology, vol. 160, no. 5, pp. 1717–1724, 2002. View at Publisher · View at Google Scholar · View at Scopus
  99. A. E. Fasth, O. Snir, A. A. Johansson et al., “Skewed distribution of proinflammatory CD4+CD28null T cells in rheumatoid arthritis,” Arthritis Research & Therapy, vol. 9, no. 5, article R87, 2007. View at Google Scholar
  100. P. B. Martens, J. J. Goronzy, D. Schaid, and C. M. Weyand, “Expansion of unusual CD4+ T cells in severe rheumatoid arthritis,” Arthritis & Rheumatism, vol. 40, no. 6, pp. 1106–1114, 1997. View at Publisher · View at Google Scholar · View at Scopus
  101. K. J. Warrington, P. D. Kent, R. L. Frye et al., “Rheumatoid arthritis is an independent risk factor for multi-vessel coronary artery disease: a case control study,” Arthritis Research & Therapy, vol. 7, no. 5, pp. R984–R991, 2005. View at Publisher · View at Google Scholar · View at Scopus
  102. Z. G. Nadareishvili, H. Li, V. Wright et al., “Elevated pro-inflammatory CD4+CD28- lymphocytes and stroke recurrence and death,” Neurology, vol. 63, no. 8, pp. 1446–1451, 2004. View at Publisher · View at Google Scholar · View at Scopus
  103. F. H. Téo, R. T. D. de Oliveira, R. L. Mamoni et al., “Characterization of CD4+CD28null T cells in patients with coronary artery disease and individuals with risk factors for atherosclerosis,” Cellular Immunology, vol. 281, no. 1, pp. 11–19, 2013. View at Publisher · View at Google Scholar · View at Scopus
  104. A. K. Yadav, A. Lal, and V. Jha, “Cytotoxic CD4+CD28null T lymphocytes, systemic inflammation and atherosclerotic risk in patients with chronic kidney disease,” Nephron Clinical Practice, vol. 120, no. 4, pp. c185–c193, 2012. View at Publisher · View at Google Scholar · View at Scopus
  105. M. D. Morgan, A. Pachnio, J. Begum et al., “CD4+CD28 T cell expansion in granulomatosis with polyangiitis (Wegener's) is driven by latent cytomegalovirus infection and is associated with an increased risk of infection and mortality,” Arthritis and Rheumatism, vol. 63, no. 7, pp. 2127–2137, 2011. View at Publisher · View at Google Scholar · View at Scopus
  106. M. Feldmann and R. N. Maini, “Anti-TNFα therapy of rheumatoid arthritis: what have we learned?” Annual Review of Immunology, vol. 19, pp. 163–196, 2001. View at Publisher · View at Google Scholar · View at Scopus
  107. S. Brugaletta, L. M. Biasucci, M. Pinnelli et al., “Novel anti-inflammatory effect of statins: Reduction of CD4+CD28null T lymphocyte frequency in patients with unstable angina,” Heart, vol. 92, no. 2, pp. 249–250, 2006. View at Publisher · View at Google Scholar · View at Scopus
  108. F. Cipollone, A. Mezzetti, E. Porreca et al., “Association between enhanced soluble CD40L and prothrombotic state in hypercholesterolemia: effects of statin therapy,” Circulation, vol. 106, no. 4, pp. 399–402, 2002. View at Publisher · View at Google Scholar · View at Scopus
  109. H. F. Alber, M. Frick, A. Suessenbacher et al., “Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease—a randomized, placebo-controlled study,” The American Heart Journal, vol. 151, no. 1, pp. 139.e1–139.e7, 2006. View at Publisher · View at Google Scholar · View at Scopus
  110. M. Scarsi, T. Ziglioli, and P. Airo, “Decreased circulating CD28-negative T cells in patients with rheumatoid arthritis treated with abatacept are correlated with clinical response,” The Journal of Rheumatology, vol. 37, no. 5, pp. 911–916, 2010. View at Publisher · View at Google Scholar · View at Scopus
  111. C. Dejaco, C. Duftner, E. Wipfler, and M. Schirmer, “A novel treatment option in rheumatoid arthritis: abatacept, a selective modulator of T-cell co-stimulation,” Wiener Medizinische Wochenschrift, vol. 159, no. 3-4, pp. 70–75, 2009. View at Publisher · View at Google Scholar · View at Scopus
  112. P. Mease, M. C. Genovese, G. Gladstein et al., “Abatacept in the treatment of patients with psoriatic arthritis: results of a six-month, multicenter, randomized, double-blind, placebo-controlled, phase II trial,” Arthritis & Rheumatism, vol. 63, no. 4, pp. 939–948, 2011. View at Publisher · View at Google Scholar · View at Scopus
  113. C. Duftner, C. Dejaco, P. Hengster et al., “Apoptotic effects of antilymphocyte globulins on human pro-inflammatory CD4+CD28 T-cells,” PLoS ONE, vol. 7, no. 3, Article ID e33939, 2012. View at Publisher · View at Google Scholar · View at Scopus
  114. C. Ziegler, J. Finke, and C. Grüllich, “Rabbit anti-T-lymphocyte globulin (ATG) persists with differential reactivity in patients' sera after full hematopoetic regeneration from allogeneic stem cell transplantation,” Transplant Immunology, vol. 30, no. 4, pp. 136–139, 2014. View at Publisher · View at Google Scholar · View at Scopus