Foxp3+ follicular regulatory T cells control the germinal center response

Nature Medicine

Volumn 17, Issue 8, 2011, Pages 975-982

  Linterman, Michelle A ^a,b   Pierson, Wim ^c   Lee, Sau K ^b   Kallies, Axel ^d   Kawamoto, Shimpei ^e   Rayner, Tim F ^a   Srivastava, Monika ^b   Divekar, Devina P ^a   Beaton, Laura ^b   Hogan, Jennifer J ^b   Fagarasan, Sidonia ^e   Liston, Adrian ^c   Smith, Kenneth G C ^a   Vinuesa, Carola G ^b  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^b Biology and Environment   (Australia)

^c UNIVERSITY OF LEUVEN   (Belgium)

^d WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH   (Australia)

^e RIKEN Center for Integrative Medical Sciences   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

B LYMPHOCYTE INDUCED MATURATION PROTEIN 1; CD28 ANTIGEN; CHEMOKINE RECEPTOR CXCR5; PROTEIN BCL 6; SIGNALING LYMPHOCYTE ACTIVATION MOLECULE ASSOCIATED PROTEIN; TRANSCRIPTION FACTOR FOXP3;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; B LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CELL POPULATION; CELL SELECTION; GERMINAL CENTER; HOMEOSTASIS; IMMUNIZATION; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; THYMUS; TISSUE REACTION;

ANIMALS; B-LYMPHOCYTES; CELL DIFFERENTIATION; DNA-BINDING PROTEINS; ENZYME-LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; FORKHEAD TRANSCRIPTION FACTORS; GERMINAL CENTER; HUMANS; IMMUNOHISTOCHEMISTRY; MEMBRANE PROTEINS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; RECEPTORS, CXCR5; REPRESSOR PROTEINS; SELF TOLERANCE; STATISTICS, NONPARAMETRIC; T-LYMPHOCYTES, REGULATORY;

EID: 79961151137     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.2425     Document Type: Article

References (50)

1. Smith, K.G.C., Light, A., Nossal, G.J.V. & Tarlinton, D.M. The extent of affinity maturation differs between the memory and antibody-forming cell compartments in the primary immune response. EMBO J. 16, 2996-3006 (1997). (Pubitemid 27234939)
2. Guo, W. et al. Somatic hypermutation as a generator of antinuclear antibodies in a murine model of systemic autoimmunity. J. Exp. Med. 207, 2225-2237 (2010).
3. Vinuesa, C.G., Sanz, I. & Cook, M.C. Dysregulation of germinal centres in autoimmune disease. Nat. Rev. Immunol. 9, 845-857 (2009).
4. Victora, G.D. et al. Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell 143, 592-605 (2010).
5. Linterman, M.A. et al. Follicular helper T cells are required for systemic autoimmunity. J. Exp. Med. 206, 561-576 (2009).
6. Vinuesa, C.G. et al. A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity. Nature 435, 452-458 (2005). (Pubitemid 40734237)
7. Kim, H.J., Verbinnen, B., Tang, X., Lu, L. & Cantor, H. Inhibition of follicular T-helper cells by CD8(+) regulatory T cells is essential for self tolerance. Nature 467, 328-332 (2010).
8. Lim, H.W., Hillsamer, P., Banham, A.H. & Kim, C.H. Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells. J. Immunol. 175, 4180-4183 (2005). (Pubitemid 41361949)
9. Lim, H.W., Hillsamer, P. & Kim, C.H. Regulatory T cells can migrate to follicles upon T cell activation and suppress germinal center-Th cells and germinal center-Th cell-driven B cell responses. J. Clin. Invest. 114, 1640-1649 (2004). (Pubitemid 40385555)
10. Fields, M.L. et al. CD4+ CD25+ regulatory T cells inhibit the maturation but not the initiation of an autoantibody response. J. Immunol. 175, 4255-4264 (2005). (Pubitemid 41361959)
11. Fontenot, J.D., Gavin, M.A. & Rudensky, A.Y. Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nat. Immunol. 4, 330-336 (2003). (Pubitemid 36432314)
12. Hori, S., Nomura, T. & Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057-1061 (2003). (Pubitemid 36222930)
13. Khattri, R., Cox, T., Yasayko, S.A. & Ramsdell, F. An essential role for Scurfin in CD4+ CD25+ T regulatory cells. Nat. Immunol. 4, 337-342 (2003). (Pubitemid 36432315)
14. Bennett, C.L. et al. The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3. Nat. Genet. 27, 20-21 (2001). (Pubitemid 32044513)
15. Wildin, R.S. et al. X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy. Nat. Genet. 27, 18-20 (2001). (Pubitemid 32044512)
16. Koch, M.A. et al. The transcription factor T-bet controls regulatory T cell homeostasis and function during type 1 inflammation. Nat. Immunol. 10, 595-602 (2009).
17. Zheng, Y. et al. Regulatory T-cell suppressor program co-opts transcription factor IRF4 to control T(H)2 responses. Nature 458, 351-356 (2009).
18. Chaudhry, A. et al. CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326, 986-991 (2009).
19. Fontenot, J.D. et al. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 22, 329-341 (2005). (Pubitemid 40387475)
20. Chtanova, T. et al. T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J. Immunol. 173, 68-78 (2004). (Pubitemid 38797327)
21. Huehn, J. et al. Developmental stage, phenotype, and migration distinguish naive-and effector/memory-like CD4+ regulatory T cells. J. Exp. Med. 199, 303-313 (2004). (Pubitemid 38252043)
22. Yoshida, K. et al. Bcl6 controls granzyme B expression in effector CD8+ T cells. Eur. J. Immunol. 36, 3146-3156 (2006). (Pubitemid 44932716)
23. Cretney, E. et al. The transcription factors Blimp-1 and IRF4 jointly control the differentiation and function of effector regulatory T cells. Nat. Immunol. 12, 304-311 (2011).
24. Linterman, M.A. et al. Roquin differentiates the specialized functions of duplicated T cell costimulatory receptor genes CD28 and ICOS. Immunity 30, 228-241 (2009).
25. Linterman, M.A. & Vinuesa, C.G. Signals that influence T follicular helper cell differentiation and function. Semin. Immunopathol. 32, 183-196 (2010).
26. Salomon, B. et al. B7/CD28 costimulation is essential for the homeostasis of the CD4+ CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12, 431-440 (2000).
27. Tang, Q. et al. Cutting edge: CD28 controls peripheral homeostasis of CD4+ CD25+ regulatory T cells. J. Immunol. 171, 3348-3352 (2003). (Pubitemid 37254533)
28. Cannons, J.L. et al. Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84. Immunity 32, 253-265 (2010).
29. Qi, H., Cannons, J.L., Klauschen, F., Schwartzberg, P.L. & Germain, R.N. SAP-controlled T-B cell interactions underlie germinal centre formation. Nature 455, 764-769 (2008).
30. Deenick, E.K. et al. Follicular helper T cell differentiation requires continuous antigen presentation that is independent of unique B cell signaling. Immunity 33, 241-253 (2010).
31. Johnston, R.J. et al. Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325, 1006-1010 (2009).
32. Nurieva, R.I. et al. Bcl6 mediates the development of T follicular helper cells. Science 325, 1001-1005 (2009).
33. Yu, D. et al. The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31, 457-468 (2009).
34. Shaffer, A.L. et al. Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program. Immunity 17, 51-62 (2002). (Pubitemid 34874618)
35. Shaffer, A.L. et al. BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control. Immunity 13, 199-212 (2000).
36. Zhou, L., Chong, M.M. & Littman, D.R. Plasticity of CD4+ T cell lineage differentiation. Immunity 30, 646-655 (2009).
37. Thornton, A.M. et al. Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3+ T regulatory cells. J. Immunol. 184, 3433-3441 (2010).
38. Kim, J.M., Rasmussen, J.P. & Rudensky, A.Y. Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of mice. Nat. Immunol. 8, 191-197 (2007). (Pubitemid 46152650)
39. Tsuji, M. et al. Preferential generation of follicular B helper T cells from Foxp3+ T cells in gut Peyer's patches. Science 323, 1488-1492 (2009).
40. Rubtsov, Y.P. et al. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces. Immunity 28, 546-558 (2008).
41. Rubtsov, Y.P. et al. Stability of the regulatory T cell lineage in vivo. Science 329, 1667-1671 (2010).
42. Chan, T.D. et al. Antigen affinity controls rapid T-dependent antibody production by driving the expansion rather than the differentiation or extrafollicular migration of early plasmablasts. J. Immunol. 183, 3139-3149 (2009).
43. Willinger, T., Freeman, T., Hasegawa, H., McMichael, A.J. & Callan, M.F. Molecular signatures distinguish human central memory from effector memory CD8 T cell subsets. J. Immunol. 175, 5895-5903 (2005). (Pubitemid 41508074)
44. Martins, G.A. et al. Transcriptional repressor Blimp-1 regulates T cell homeostasis and function. Nat. Immunol. 7, 457-465 (2006).
45. Schmidt, E.M. et al. Ctla-4 controls regulatory T cell peripheral homeostasis and is required for suppression of pancreatic islet autoimmunity. J. Immunol. 182, 274-282 (2009).
46. Wing, K. et al. CTLA-4 control over Foxp3+ regulatory T cell function. Science 322, 271-275 (2008).
47. Vinuesa, C.G., Tangye, S.G., Moser, B. & Mackay, C.R. Follicular B helper T cells in antibody responses and autoimmunity. Natl. Rev. Immunol. 5, 853-865 (2005). (Pubitemid 41581667)
48. Hsu, H.C. et al. Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat. Immunol. 9, 166-175 (2008).
49. Gräbner, R. et al. Lymphotoxin beta receptor signaling promotes tertiary lymphoid organogenesis in the aorta adventitia of aged ApoE?/? mice. J. Exp. Med. 206, 233-248 (2009).
50. Wehner, J.R. et al. B cells and plasma cells in coronaries of chronically rejected cardiac transplants. Transplantation 89, 1141-1148 (2010).