IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Regulatory T Cells in B Cell Follicles

  • Received : 2014.08.12
  • Accepted : 2014.09.12
  • Published : 2014.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

Understanding germinal center reactions is crucial not only for the design of effective vaccines against infectious agents and malignant cells but also for the development of therapeutic intervention for the treatment of antibody-mediated immune disorders. Recent advances in this field have revealed specialized subsets of T cells necessary for the control of B cell responses in the follicle. These cells include follicular regulatory T cells and Qa-1-restricted cluster of differentiation $(CD)8^+$ regulatory T cells. In this review, we discuss the current knowledge related to the role of regulatory T cells in the B cell follicle.

Keywords

References

  1. Wahren-Herlenius, M. and T. Dorner. 2013. Immunopathogenic mechanisms of systemic autoimmune disease. Lancet 382: 819-831. https://doi.org/10.1016/S0140-6736(13)60954-X
  2. Paul, W. E. and J. Ohara. 1987. B-cell stimulatory factor-1/interleukin 4. Annu. Rev. Immunol. 5: 429-459. https://doi.org/10.1146/annurev.iy.05.040187.002241
  3. Banchereau, J., P. P. de, A. Valle, E. Garcia, and F. Rousset. 1991. Long-term human B cell lines dependent on interleukin-4 and antibody to CD40. Science 251: 70-72. https://doi.org/10.1126/science.1702555
  4. Arpin, C., J. Dechanet, K. C. Van, P. Merville, G. Grouard, F. Briere, J. Banchereau, and Y. J. Liu. 1995. Generation of memory B cells and plasma cells in vitro. Science 268: 720-722. https://doi.org/10.1126/science.7537388
  5. Johnston, R. J., A. C. Poholek, D. DiToro, I. Yusuf, D. Eto, B. Barnett, A. L. Dent, J. Craft, and S. Crotty. 2009. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325: 1006-1010. https://doi.org/10.1126/science.1175870
  6. Nurieva, R. I., Y. Chung, G. J. Martinez, X. O. Yang, S. Tanaka, T. D. Matskevitch, Y. H. Wang, and C. Dong. 2009. Bcl6 mediates the development of T follicular helper cells. Science 325: 1001-1005. https://doi.org/10.1126/science.1176676
  7. Yu, D., S. Rao, L. M. Tsai, S. K. Lee, Y. He, E. L. Sutcliffe, M. Srivastava, M. Linterman, L. Zheng, N. Simpson, J. I. Ellyard, I. A. Parish, C. S. Ma, Q. J. Li, C. R. Parish, C. R. Mackay, and C. G. Vinuesa. 2009. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31: 457-468. https://doi.org/10.1016/j.immuni.2009.07.002
  8. Fillatreau, S., C. H. Sweenie, M. J. McGeachy, D. Gray, and S. M. Anderton. 2002. B cells regulate autoimmunity by provision of IL-10. Nat. Immunol. 3: 944-950.
  9. Mizoguchi, A., E. Mizoguchi, H. Takedatsu, R. S. Blumberg, and A. K. Bhan. 2002. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16: 219-230. https://doi.org/10.1016/S1074-7613(02)00274-1
  10. Mauri, C., D. Gray, N. Mushtaq, and M. Londei. 2003. Prevention of arthritis by interleukin 10-producing B cells. J. Exp. Med. 197: 489-501. https://doi.org/10.1084/jem.20021293
  11. Victora, G. D. and M. C. Nussenzweig. 2012. Germinal centers. Annu. Rev. Immunol. 30: 429-457. https://doi.org/10.1146/annurev-immunol-020711-075032
  12. MacLennan, I. C., K. M. Toellner, A. F. Cunningham, K. Serre, D. M. Sze, E. Zuniga, M. C. Cook, and C. G. Vinuesa. 2003. Extrafollicular antibody responses. Immunol. Rev. 194: 8-18. https://doi.org/10.1034/j.1600-065X.2003.00058.x
  13. Vinuesa, C. G., M. A. Linterman, C. C. Goodnow, and K. L. Randall. 2010. T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol. Rev. 237: 72-89. https://doi.org/10.1111/j.1600-065X.2010.00937.x
  14. Craft, J. E. 2012. Follicular helper T cells in immunity and systemic autoimmunity. Nat. Rev. Rheumatol. 8: 337-347. https://doi.org/10.1038/nrrheum.2012.58
  15. Fazilleau, N., L. Mark, L. J. Heyzer-Williams, and M. G. Heyzer-Williams. 2009. Follicular helper T cells: lineage and location. Immunity 30: 324-335. https://doi.org/10.1016/j.immuni.2009.03.003
  16. Crotty, S. 2011. Follicular helper CD4 T cells (TFH). Annu. Rev. Immunol. 29: 621-663. https://doi.org/10.1146/annurev-immunol-031210-101400
  17. King, I. L. and M. Mohrs. 2009. IL-4-producing $CD4^{+}$ T cells in reactive lymph nodes during helminth infection are T follicular helper cells. J. Exp. Med. 206: 1001-1007. https://doi.org/10.1084/jem.20090313
  18. Nurieva, R. I., Y. Chung, D. Hwang, X. O. Yang, H. S. Kang, L. Ma, Y. H. Wang, S. S. Watowich, A. M. Jetten, Q. Tian, and C. Dong. 2008. Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 29: 138-149. https://doi.org/10.1016/j.immuni.2008.05.009
  19. Liu, X., X. Chen, B. Zhong, A. Wang, X. Wang, F. Chu, R. I. Nurieva, X. Yan, P. Chen, L. G. van der Flier, H. Nakatsukasa, S. S. Neelapu, W. Chen, H. Clevers, Q. Tian, H. Qi, L. Wei, and C. Dong. 2014. Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development. Nature 507: 513-518. https://doi.org/10.1038/nature12910
  20. Diehl, S. A., H. Schmidlin, M. Nagasawa, B. Blom, and H. Spits. 2012. IL-6 triggers IL-21 production by human $ CD4^{+}$ T cells to drive STAT3-dependent plasma cell differentiation in B cells. Immunol. Cell Biol. 90: 802-811. https://doi.org/10.1038/icb.2012.17
  21. Eddahri, F., S. Denanglaire, F. Bureau, R. Spolski, W. J. Leonard, O. Leo, and F. Andris. 2009. Interleukin-6/STAT3 signaling regulates the ability of naive T cells to acquire B-cell help capacities. Blood 113: 2426-2433. https://doi.org/10.1182/blood-2008-04-154682
  22. Ma, C. S., D. T. Avery, A. Chan, M. Batten, J. Bustamante, S. Boisson-Dupuis, P. D. Arkwright, A. Y. Kreins, D. Averbuch, D. Engelhard, K. Magdorf, S. S. Kilic, Y. Minegishi, S. Nonoyama, M. A. French, S. Choo, J. M. Smart, J. Peake, M. Wong, P. Gray, M. C. Cook, D. A. Fulcher, J. L. Casanova, E. K. Deenick, and S. G. Tangye. 2012. Functional STAT3 deficiency compromises the generation of human T follicular helper cells. Blood 119: 3997-4008. https://doi.org/10.1182/blood-2011-11-392985
  23. Betz, B. C., K. L. Jordan-Williams, C. Wang, S. G. Kang, J. Liao, M. R. Logan, C. H. Kim, and E. J. Taparowsky. 2010. Batf coordinates multiple aspects of B and T cell function required for normal antibody responses. J. Exp. Med. 207: 933-942. https://doi.org/10.1084/jem.20091548
  24. Ise, W., M. Kohyama, B. U. Schraml, T. Zhang, B. Schwer, U. Basu, F. W. Alt, J. Tang, E. M. Oltz, T. L. Murphy, and K. M. Murphy. 2011. The transcription factor BATF controls the global regulators of class-switch recombination in both B cells and T cells. Nat. Immunol. 12: 536-543. https://doi.org/10.1038/ni.2037
  25. Biswas, P. S., S. Gupta, R. A. Stirzaker, V. Kumar, R. Jessberger, T. T. Lu, G. Bhagat, and A. B. Pernis. 2012. Dual regulation of IRF4 function in T and B cells is required for the coordination of T-B cell interactions and the prevention of autoimmunity. J. Exp. Med. 209: 581-596. https://doi.org/10.1084/jem.20111195
  26. Bollig, N., A. Brustle, K. Kellner, W. Ackermann, E. Abass, H. Raifer, B. Camara, C. Brendel, G. Giel, E. Bothur, M. Huber, C. Paul, A. Elli, R. A. Kroczek, R. Nurieva, C. Dong, R. Jacob, T. W. Mak, and M. Lohoff. 2012. Transcription factor IRF4 determines germinal center formation through follicular T-helper cell differentiation. Proc. Natl. Acad. Sci. U. S. A. 109: 8664-8669. https://doi.org/10.1073/pnas.1205834109
  27. Baumjohann, D., R. Kageyama, J. M. Clingan, M. M. Morar, S. Patel, K. D. de, O. Bannard, J. A. Bluestone, M. Matloubian, K. M. Ansel, and L. T. Jeker. 2013. The microRNA cluster miR-17 approximately 92 promotes TFH cell differentiation and represses subset-inappropriate gene expression. Nat. Immunol. 14: 840-848. https://doi.org/10.1038/ni.2642
  28. Kang, S. G., W. H. Liu, P. Lu, H. Y. Jin, H. W. Lim, J. Shepherd, D. Fremgen, E. Verdin, M. B. Oldstone, H. Qi, J. R. Teijaro, and C. Xiao. 2013. MicroRNAs of the miR-17 approximately 92 family are critical regulators of T(FH) differentiation. Nat. Immunol. 14: 849-857. https://doi.org/10.1038/ni.2648
  29. Dienz, O., S. M. Eaton, J. P. Bond, W. Neveu, D. Moquin, R. Noubade, E. M. Briso, C. Charland, W. J. Leonard, G. Ciliberto, C. Teuscher, L. Haynes, and M. Rincon. 2009. The induction of antibody production by IL-6 is indirectly mediated by IL-21 produced by $ CD4^{+}$ T cells. J. Exp. Med. 206: 69-78. https://doi.org/10.1084/jem.20081571
  30. Eto, D., C. Lao, D. DiToro, B. Barnett, T. C. Escobar, R. Kageyama, I. Yusuf, and S. Crotty. 2011. IL-21 and IL-6 are critical for different aspects of B cell immunity and redundantly induce optimal follicular helper CD4 T cell (Tfh) differentiation. PLoS One 6: e17739. https://doi.org/10.1371/journal.pone.0017739
  31. Nakayamada, S., Y. Kanno, H. Takahashi, D. Jankovic, K. T. Lu, T. A. Johnson, H. W. Sun, G. Vahedi, O. Hakim, R. Handon, P. L. Schwartzberg, G. L. Hager, and J. J. O'Shea. 2011. Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity 35: 919-931. https://doi.org/10.1016/j.immuni.2011.11.012
  32. Schmitt, N., R. Morita, L. Bourdery, S. E. Bentebibel, S. M. Zurawski, J. Banchereau, and H. Ueno. 2009. Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12. Immunity 31: 158-169. https://doi.org/10.1016/j.immuni.2009.04.016
  33. Ballesteros-Tato, A., B. Leon, B. A. Graf, A. Moquin, P. S. Adams, F. E. Lund, and T. D. Randall. 2012. Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation. Immunity 36: 847-856. https://doi.org/10.1016/j.immuni.2012.02.012
  34. Johnston, R. J., Y. S. Choi, J. A. Diamond, J. A. Yang, and S. Crotty. 2012. STAT5 is a potent negative regulator of TFH cell differentiation. J. Exp. Med. 209: 243-250. https://doi.org/10.1084/jem.20111174
  35. Sakaguchi, S., N. Sakaguchi, M. Asano, M. Itoh, and M. Toda. 1995. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155: 1151-1164.
  36. Sakaguchi, S., T. Yamaguchi, T. Nomura, and M. Ono. 2008. Regulatory T cells and immune tolerance. Cell 133: 775-787. https://doi.org/10.1016/j.cell.2008.05.009
  37. Chaudhry, A., D. Rudra, P. Treuting, R. M. Samstein, Y. Liang, A. Kas, and A. Y. Rudensky. 2009. $ CD4^{+}$ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326: 986-991. https://doi.org/10.1126/science.1172702
  38. Chung, Y., S. Tanaka, F. Chu, R. I. Nurieva, G. J. Martinez, S. Rawal, Y. H. Wang, H. Lim, J. M. Reynolds, X. H. Zhou, H. M. Fan, Z. M. Liu, S. S. Neelapu, and C. Dong. 2011. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat. Med. 17: 983-988. https://doi.org/10.1038/nm.2426
  39. Koch, M. A., G. Tucker-Heard, N. R. Perdue, J. R. Killebrew, K. B. Urdahl, and D. J. Campbell. 2009. The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat. Immunol. 10: 595-602. https://doi.org/10.1038/ni.1731
  40. Linterman, M. A., W. Pierson, S. K. Lee, A. Kallies, S. Kawamoto, T. F. Rayner, M. Srivastava, D. P. Divekar, L. Beaton, J. J. Hogan, S. Fagarasan, A. Liston, K. G. Smith, and C. G. Vinuesa. 2011. $Foxp3^{+}$ follicular regulatory T cells control the germinal center response. Nat. Med. 17: 975-982. https://doi.org/10.1038/nm.2425
  41. Zheng, Y., A. Chaudhry, A. Kas, P. deRoos, J. M. Kim, T. T. Chu, L. Corcoran, P. Treuting, U. Klein, and A. Y. Rudensky. 2009. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses. Nature 458: 351-356. https://doi.org/10.1038/nature07674
  42. Lu, L. F., T. H. Thai, D. P. Calado, A. Chaudhry, M. Kubo, K. Tanaka, G. B. Loeb, H. Lee, A. Yoshimura, K. Rajewsky, and A. Y. Rudensky. 2009. Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells by targeting SOCS1 protein. Immunity 30: 80-91. https://doi.org/10.1016/j.immuni.2008.11.010
  43. Vinuesa, C. G., I. Sanz, and M. C. Cook. 2009. Dysregulation of germinal centres in autoimmune disease. Nat. Rev. Immunol. 9: 845-857. https://doi.org/10.1038/nri2637
  44. Lim, H. W., P. Hillsamer, and C. H. Kim. 2004. Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell-driven B cell responses. J. Clin. Invest. 114: 1640-1649. https://doi.org/10.1172/JCI200422325
  45. Lim, H. W., P. Hillsamer, A. H. Banham, and C. H. Kim. 2005. Cutting edge: direct suppression of B cells by $ CD4^{+}$ $ CD25^{+}$ regulatory T cells. J. Immunol. 175: 4180-4183. https://doi.org/10.4049/jimmunol.175.7.4180
  46. Neumann, C., F. Heinrich, K. Neumann, V. Junghans, M. F. Mashreghi, J. Ahlers, M. Janke, C. Rudolph, N. Mockel-Tenbrinck, A. A. Kuhl, M. M. Heimesaat, C. Esser, S. H. Im, A. Radbruch, S. Rutz, and A. Scheffold. 2014. Role of Blimp-1 in programing Th effector cells into IL-10 producers. J. Exp. Med. 211: 1807-1819 https://doi.org/10.1084/jem.20131548
  47. Sun, J., H. Dodd, E. K. Moser, R. Sharma, and T. J. Braciale. 2011. $ CD4^{+}$ T cell help and innate-derived IL-27 induce Blimp-1-dependent IL-10 production by antiviral CTLs. Nat. Immunol. 12: 327-334. https://doi.org/10.1038/ni.1996
  48. Sage, P. T., L. M. Francisco, C. V. Carman, and A. H. Sharpe. 2013. The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood. Nat. Immunol. 14: 152-161.
  49. Choi, Y. S., R. Kageyama, D. Eto, T. C. Escobar, R. J. Johnston, L. Monticelli, C. Lao, and S. Crotty. 2011. ICOS receptor instructs T follicular helper cell versus effector cell differentiation via induction of the transcriptional repressor Bcl6. Immunity 34: 932-946. https://doi.org/10.1016/j.immuni.2011.03.023
  50. Choi, Y. S., J. A. Yang, and S. Crotty. 2013. Dynamic regulation of Bcl6 in follicular helper CD4 T (Tfh) cells. Curr. Opin. Immunol. 25: 366-372. https://doi.org/10.1016/j.coi.2013.04.003
  51. Hildebrand, J. M., Z. Yi, C. M. Buchta, J. Poovassery, L. L. Stunz, and G. A. Bishop. 2011. Roles of tumor necrosis factor receptor associated factor 3 (TRAF3) and TRAF5 in immune cell functions. Immunol. Rev. 244: 55-74. https://doi.org/10.1111/j.1600-065X.2011.01055.x
  52. Xie, P., Z. J. Kraus, L. L. Stunz, Y. Liu, and G. A. Bishop. 2011. TNF receptor-associated factor 3 is required for T cell-mediated immunity and TCR/CD28 signaling. J. Immunol. 186: 143-155. https://doi.org/10.4049/jimmunol.1000290
  53. Chang, J. H., H. Hu, J. Jin, N. Puebla-Osorio, Y. Xiao, B. E. Gilbert, R. Brink, S. E. Ullrich, and S. C. Sun. 2014. TRAF3 regulates the effector function of regulatory T cells and humoral immune responses. J. Exp. Med. 211: 137-151. https://doi.org/10.1084/jem.20131019
  54. Watanabe, M., S. Nakajima, K. Ohnuki, S. Ogawa, M. Yamashita, T. Nakayama, Y. Murakami, K. Tanabe, and R. Abe. 2012. AP-1 is involved in ICOS gene expression downstream of TCR/CD28 and cytokine receptor signaling. Eur. J. Immunol. 42: 1850-1862. https://doi.org/10.1002/eji.201141897
  55. Tan, A. H., S. C. Wong, and K. P. Lam. 2006. Regulation of mouse inducible costimulator (ICOS) expression by Fyn-NFATc2 and ERK signaling in T cells. J. Biol. Chem. 281: 28666-28678. https://doi.org/10.1074/jbc.M604081200
  56. Shevach, E. M. 2009. Mechanisms of $foxp3^{+}$ T regulatory cell-mediated suppression. Immunity 30: 636-645. https://doi.org/10.1016/j.immuni.2009.04.010
  57. Wing, K., Y. Onishi, P. Prieto-Martin, T. Yamaguchi, M. Miyara, Z. Fehervari, T. Nomura, and S. Sakaguchi. 2008. CTLA-4 control over $Foxp3^{+}$ regulatory T cell function. Science 322: 271-275. https://doi.org/10.1126/science.1160062
  58. Okazaki, T. and T. Honjo. 2006. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol. 27: 195-201. https://doi.org/10.1016/j.it.2006.02.001
  59. Linterman, M. A., W. Pierson, S. K. Lee, A. Kallies, S. Kawamoto, T. F. Rayner, M. Srivastava, D. P. Divekar, L. Beaton, J. J. Hogan, S. Fagarasan, A. Liston, K. G. Smith, and C. G. Vinuesa. 2011. $Foxp3^{+}$ follicular regulatory T cells control the germinal center response. Nat. Med. 17: 975-982. https://doi.org/10.1038/nm.2425
  60. Okazaki, T., Y. Tanaka, R. Nishio, T. Mitsuiye, A. Mizoguchi, J. Wang, M. Ishida, H. Hiai, A. Matsumori, N. Minato, and T. Honjo. 2003. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat. Med. 9: 1477-1483. https://doi.org/10.1038/nm955
  61. Okazaki, T., Y. Otaka, J. Wang, H. Hiai, T. Takai, J. V. Ravetch, and T. Honjo. 2005. Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice. J. Exp. Med. 202: 1643-1648. https://doi.org/10.1084/jem.20051984
  62. Good-Jacobson, K. L., C. G. Szumilas, L. Chen, A. H. Sharpe, M. M. Tomayko, and M. J. Shlomchik. 2010. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat. Immunol. 11: 535-542. https://doi.org/10.1038/ni.1877
  63. Nakamura, K., A. Kitani, and W. Strober. 2001. Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J. Exp. Med. 194: 629-644. https://doi.org/10.1084/jem.194.5.629
  64. Jeannin, P., S. Lecoanet, Y. Delneste, J. F. Gauchat, and J. Y. Bonnefoy. 1998. IgE versus IgG4 production can be differentially regulated by IL-10. J. Immunol. 160: 3555-3561.
  65. Coffman, R. L., D. A. Lebman, and B. Shrader. 1989. Transforming growth factor beta specifically enhances IgA production by lipopolysaccharide-stimulated murine B lymphocytes. J. Exp. Med. 170: 1039-1044. https://doi.org/10.1084/jem.170.3.1039
  66. Sarantopoulos, S., L. Lu, and H. Cantor. 2004. Qa-1 restriction of $CD8^{+}$ suppressor T cells. J. Clin. Invest. 114: 1218-1221. https://doi.org/10.1172/JCI23152
  67. Hu, D., K. Ikizawa, L. Lu, M. E. Sanchirico, M. L. Shinohara, and H. Cantor. 2004. Analysis of regulatory CD8 T cells in Qa-1-deficient mice. Nat. Immunol. 5: 516-523. https://doi.org/10.1038/ni1063
  68. Lu, L., K. Ikizawa, D. Hu, M. B. Werneck, K. W. Wucherpfennig, and H. Cantor. 2007. Regulation of activated $ CD4^{+}$ T cells by NK cells via the Qa-1-NKG2A inhibitory pathway. Immunity 26: 593-604. https://doi.org/10.1016/j.immuni.2007.03.017
  69. Lu, L., H. J. Kim, M. B. Werneck, and H. Cantor. 2008. Regulation of $CD8^{+}$ regulatory T cells: Interruption of the NKG2A-Qa-1 interaction allows robust suppressive activity and resolution of autoimmune disease. Proc. Natl. Acad. Sci. U. S. A. 105: 19420-19425. https://doi.org/10.1073/pnas.0810383105
  70. Cantor, H. and E. A. Boyse. 1975. Functional subclasses of T-lymphocytes bearing different Ly antigens. I. The generation of functionally distinct T-cell subclasses is a differentiative process independent of antigen. J. Exp. Med. 141: 1376-1389. https://doi.org/10.1084/jem.141.6.1376
  71. Cantor, H., F. W. Shen, and E. A. Boyse. 1976. Separation of helper T cells from suppressor T cells expressing different Ly components. II. Activation by antigen: after immunization, antigen-specific suppressor and helper activities are mediated by distinct T-cell subclasses. J. Exp. Med. 143: 1391-1340. https://doi.org/10.1084/jem.143.6.1391
  72. Kim, H. J., B. Verbinnen, X. Tang, L. Lu, and H. Cantor. 2010. Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance. Nature 467: 328-332. https://doi.org/10.1038/nature09370
  73. Kim, H. J. and H. Cantor. 2011. Regulation of self-tolerance by Qa-1-restricted CD8(+) regulatory T cells. Semin. Immunol. 23: 446-452. https://doi.org/10.1016/j.smim.2011.06.001
  74. Kim, H. J., X. Wang, S. Radfar, T. J. Sproule, D. C. Roopenian, and H. Cantor. 2011. $CD8^{+}$ T regulatory cells express the Ly49 Class I MHC receptor and are defective in autoimmune prone B6-Yaa mice. Proc. Natl. Acad. Sci. U. S. A 108: 2010-2015. https://doi.org/10.1073/pnas.1018974108
  75. Leavenworth, J. W., X. Tang, H. J. Kim, X. Wang, and H. Cantor. 2013. Amelioration of arthritis through mobilization of peptide-specific $CD8^{+}$ regulatory T cells. J. Clin. Invest. 123: 1382-1389. https://doi.org/10.1172/JCI66938
  76. Jiang, H., S. M. Canfield, M. P. Gallagher, H. H. Jiang, Y. Jiang, Z. Zheng, and L. Chess. 2010. HLA-E-restricted regulatory CD8(+) T cells are involved in development and control of human autoimmune type 1 diabetes. J. Clin. Invest. 120: 3641-3650. https://doi.org/10.1172/JCI43522
  77. Correale, J. and A. Villa. 2008. Isolation and characterization of $CD8^{+}$ regulatory T cells in multiple sclerosis. J. Neuroimmunol. 195: 121-134. https://doi.org/10.1016/j.jneuroim.2007.12.004
  78. Lu, L. F., M. P. Boldin, A. Chaudhry, L. L. Lin, K. D. Taganov, T. Hanada, A. Yoshimura, D. Baltimore, and A. Y. Rudensky. 2010. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell 142: 914-929. https://doi.org/10.1016/j.cell.2010.08.012
  79. de Kouchkovsky, D., J. H. Esensten, W. L. Rosenthal, M. M. Morar, J. A. Bluestone, and L. T. Jeker. 2013. microRNA-17-92 regulates IL-10 production by regulatory T cells and control of experimental autoimmune encephalomyelitis. J. Immunol. 191: 1594-1605. https://doi.org/10.4049/jimmunol.1203567

Cited by

  1. Therapeutics to block autoantibody initiation and propagation in systemic lupus erythematosus and rheumatoid arthritis vol.7, pp.280, 2014, https://doi.org/10.1126/scitranslmed.aaa3809
  2. Blockade of STAT3 in T Cells Inhibits Germinal Center Reactions against Intranasal Allergens vol.24, pp.3, 2014, https://doi.org/10.4062/biomolther.2015.160
  3. Enforced Expression of CXCR5 Drives T Follicular Regulatory-Like Features in Foxp3+ T Cells vol.25, pp.2, 2017, https://doi.org/10.4062/biomolther.2016.075
  4. Inflammation regulates 11β-hydroxysteroid dehydrogenase type 1 differentially in specific compartments of the gut mucosal immune system vol.126, pp.None, 2014, https://doi.org/10.1016/j.steroids.2017.07.007
  5. Atherogenic dyslipidemia promotes autoimmune follicular helper T cell responses via IL-27 vol.19, pp.6, 2014, https://doi.org/10.1038/s41590-018-0102-6
  6. Immune cell subset differentiation and tissue inflammation vol.11, pp.1, 2014, https://doi.org/10.1186/s13045-018-0637-x