The T-cell receptor repertoire of regulatory T cells

Immunology

Volumn 125, Issue 4, 2008, Pages 450-458

  Pacholczyk, Rafal ^a   Kern, Joanna ^a  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

Author keywords

MHC HLA; Regulatory T cell; T cells; T cell receptor; Thymus

Indexed keywords

CYTOKINE; INTERLEUKIN 2 RECEPTOR ALPHA; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3;

ANTIGEN PRESENTING CELL; ANTIGEN RECOGNITION; AUTOIMMUNE DISEASE; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; GENETIC VARIABILITY; GRAFT VERSUS HOST REACTION; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; LEISHMANIA MAJOR; LYMPHOCYTE DIFFERENTIATION; MAJOR HISTOCOMPATIBILITY COMPLEX; NONHUMAN; NUDE MOUSE; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; SIGNAL TRANSDUCTION; THYMUS; TRANSGENIC MOUSE;

ANIMALS; EPITOPES; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; MAJOR HISTOCOMPATIBILITY COMPLEX; RECEPTORS, ANTIGEN, T-CELL; SELF TOLERANCE; T-LYMPHOCYTES, REGULATORY; THYMUS GLAND;

EID: 55449084935     PISSN: 00192805     EISSN: 13652567     Source Type: Journal    
DOI: 10.1111/j.1365-2567.2008.02992.x     Document Type: Review

References (99)

1. Hogquist KA, Baldwin TA, Jameson SC. Central tolerance: learning self-control in the thymus. Nat Rev Immunol 2005 5 : 772 82.
2. Davis MM. T cell receptor gene diversity and selection. Annu Rev Biochem 1990 59 : 475 96.
3. Kappler JW, Roehm N, Marrack P. T cell tolerance by clonal elimination in the thymus. Cell 1987 49 : 273 80.
4. Kisielow P, Bluthmann H, Staerz UD, Steinmetz M, von Boehmer H. Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature 1988 333 : 742 6.
5. Stockinger B. T lymphocyte tolerance: from thymic deletion to peripheral control mechanisms. Adv Immunol 1999 71 : 229 65.
6. Piccirillo CA, Shevach EM. Naturally-occurring CD4+CD25+ immunoregulatory T cells: central players in the arena of peripheral tolerance. Semin Immunol 2004 16 : 81 8.
7. Sakaguchi S. Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 2004 22 : 531 62.
8. Chen W, Jin W, Hardegen N, Lei KJ, Li L, Marinos N, McGrady G, Wahl SM. Conversion of peripheral CD4+. J Exp Med 2003 198 : 1875 86.
9. Walker MR, Kasprowicz DJ, Gersuk VH, Benard A, Van Landeghen M, Buckner JH, Ziegler SF. Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+. J Clin Invest 2003 112 : 1437 43.
10. Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev Immunol 2003 3 : 253 7.
11. Chatila T. Molecular mechanisms of regulatory T cell development. J Clin Immunol 2008 [Epub ahead of print].
12. Nishizuka Y, Sakakura T. Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 1969 166 : 753 5.
13. Penhale WJ, Farmer A, McKenna RP, Irvine WJ. Spontaneous thyroiditis in thymectomized and irradiated Wistar rats. Clin Exp Immunol 1973 15 : 225 36.
14. Penhale WJ, Irvine WJ, Inglis JR, Farmer A. Thyroiditis in T cell-depleted rats: suppression of the autoallergic response by reconstitution with normal lymphoid cells. Clin Exp Immunol 1976 25 : 6 16.
15. Sakaguchi S, Takahashi T, Nishizuka Y. Study on cellular events in post-thymectomy autoimmune oophoritis in mice. II. Requirement of Lyt-1 cells in normal female mice for the prevention of oophoritis. J Exp Med 1982 156 : 1577 86.
16. Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. 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 1995 155 : 1151 64.
17. Suri-Payer E, Amar AZ, Thornton AM, Shevach EM. CD4+CD25+ T cells inhibit both the induction and effector function of autoreactive T cells and represent a unique lineage of immunoregulatory cells. J Immunol 1998 160 : 1212 8.
18. Shevach EM. Certified professionals: CD4(+)CD25(+) suppressor T cells. J Exp Med 2001 193 : F41 6.
19. Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003 4 : 330 6.
20. Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003 299 : 1057 61.
21. Khattri R, Cox T, Yasayko SA, Ramsdell F. An essential role for Scurfin in CD4+CD25+ T regulatory cells. Nat Immunol 2003 4 : 337 42.
22. Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity 2005 22 : 329 41.
23. Gavin MA, Rasmussen JP, Fontenot JD, Vasta V, Manganiello VC, Beavo JA, Rudensky AY. Foxp3-dependent programme of regulatory T-cell differentiation. Nature 2007 445 : 771 5.
24. Wan YY, Flavell RA. Regulatory T-cell functions are subverted and converted owing to attenuated Foxp3 expression. Nature 2007 445 : 766 70.
25. Zheng Y, Rudensky AY. Foxp3 in control of the regulatory T cell lineage. Nat Immunol 2007 8 : 457 62.
26. Itoh M, Takahashi T, Sakaguchi N, Kuniyasu Y, Shimizu J, Otsuka F, Sakaguchi S. Thymus and autoimmunity: production of CD25+CD4+ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J Immunol 1999 162 : 5317 26.
27. Olivares-Villagomez D, Wensky AK, Wang Y, Lafaille JJ. Repertoire requirements of CD4+ T cells that prevent spontaneous autoimmune encephalomyelitis. J Immunol 2000 164 : 5499 507.
28. Takahashi T, Kuniyasu Y, Toda M, Sakaguchi N, Itoh M, Iwata M, Shimizu J, Sakaguchi S. Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 1998 10 : 1969 80.
29. Thornton AM, Shevach EM. CD4+CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 1998 188 : 287 96.
30. Apostolou I, Sarukhan A, Klein L, von Boehmer H. Origin of regulatory T cells with known specificity for antigen. Nat Immunol 2002 3 : 756 63.
31. Klein L, Khazaie K, von Boehmer H. In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro. Proc Natl Acad Sci USA 2003 100 : 8886 91.
32. Thornton AM, Shevach EM. Suppressor effector function of CD4+CD25+ immunoregulatory T cells is antigen nonspecific. J Immunol 2000 164 : 183 90.
33. Kojima A, Taguchi O, Nishizuka Y. Experimental production of possible autoimmune gastritis followed by macrocytic anemia in athymic nude mice. Lab Invest 1980 42 : 387 95.
34. Kojima A, Prehn RT. Genetic susceptibility to post-thymectomy autoimmune diseases in mice. Immunogenetics 1981 14 : 15 27.
35. Tung KS, Smith S, Teuscher C, Cook C, Anderson RE. Murine autoimmune oophoritis, epididymoorchitis, and gastritis induced by day 3 thymectomy. Immunopathology. Am J Pathol 1987 126 : 293 302.
36. Asano M, Toda M, Sakaguchi N, Sakaguchi S. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J Exp Med 1996 184 : 387 96.
37. Jordan MS, Boesteanu A, Reed AJ, Petrone AL, Holenbeck AE, Lerman MA, Naji A, Caton AJ. Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol 2001 2 : 301 6.
38. Kawahata K, Misaki Y, Yamauchi M, Tsunekawa S, Setoguchi K, Miyazaki JI, Yamamoto K. Generation of CD4+CD25+ regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from nonautoreactive T cells by endogenous TCR expression. J Immunol 2002 168 : 4399 405.
39. Walker LS, Chodos A, Eggena M, Dooms H, Abbas AK. Antigen-dependent proliferation of CD4+ CD25+ regulatory T cells in vivo. J Exp Med 2003 198 : 249 58.
40. Lohr J, Knoechel B, Jiang S, Sharpe AH, Abbas AK. The inhibitory function of B7 costimulators in T cell responses to foreign and self-antigens. Nat Immunol 2003 4 : 664 9.
41. D'Cruz LM, Klein L. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol 2005 6 : 1152 9.
42. van Santen HM, Benoist C, Mathis D. Number of T reg cells that differentiate does not increase upon encounter of agonist ligand on thymic epithelial cells. J Exp Med 2004 200 : 1221 30.
43. Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC. Aire regulates negative selection of organ-specific T cells. Nat Immunol 2003 4 : 350 4.
44. Bonasio R, Scimone ML, Schaerli P, Grabie N, Lichtman AH, von Andrian UH. Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nat Immunol 2006 7 : 1092 100.
45. Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 2002 420 : 502 7.
46. Cohen JL, Trenado A, Vasey D, Klatzmann D, Salomon BL. CD4(+)CD25(+) immunoregulatory T Cells: new therapeutics for graft-versus-host disease. J Exp Med 2002 196 : 401 6.
47. Hoffmann P, Ermann J, Edinger M, Fathman CG, Strober S. Donor-type CD4(+)CD25(+) regulatory T cells suppress lethal acute graft-versus-host disease after allogeneic bone marrow transplantation. J Exp Med 2002 196 : 389 99.
48. Taylor PA, Lees CJ, Blazar BR. The infusion of ex vivo activated and expanded CD4(+)CD25(+) immune regulatory cells inhibits graft-versus-host disease lethality. Blood 2002 99 : 3493 9.
49. Suvas S, Kumaraguru U, Pack CD, Lee S, Rouse BT. CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses. J Exp Med 2003 198 : 889 901.
50. Edinger M, Hoffmann P, Ermann J, Drago K, Fathman CG, Strober S, Negrin RS. CD4+CD25+ regulatory T cells preserve graft-versus-tumor activity while inhibiting graft-versus-host disease after bone marrow transplantation. Nat Med 2003 9 : 1144 50.
51. Lerman MA, Larkin J III., Cozzo C, Jordan MS, Caton AJ. CD4+ CD25+ regulatory T cell repertoire formation in response to varying expression of a neo-self-antigen. J Immunol 2004 173 : 236 44.
52. Ochando JC, Yopp AC, Yang Y et al. Lymph node occupancy is required for the peripheral development of alloantigen-specific Foxp3+ regulatory T cells. J Immunol 2005 174 : 6993 7005.
53. Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G. Ex vivo isolation and characterization of CD4+CD25+ T cells with regulatory properties from human blood. J Exp Med 2001 193 : 1303 10.
54. Pacholczyk R, Kraj P, Ignatowicz L. Peptide specificity of thymic selection of CD4+CD25+ T cells. J Immunol 2002 168 : 613 20.
55. Jiang S, Camara N, Lombardi G, Lechler RI. Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex vivo. Blood 2003 102 : 2180 6.
56. Romagnoli P, Hudrisier D, van Meerwijk JP. Preferential recognition of self antigens despite normal thymic deletion of CD4(+)CD25(+) regulatory T cells. J Immunol 2002 168 : 1644 8.
57. Hsieh CS, Liang Y, Tyznik AJ, Self SG, Liggitt D, Rudensky AY. Recognition of the peripheral self by naturally arising CD25+ CD4+ T cell receptors. Immunity 2004 21 : 267 77.
58. Hsieh CS, Zheng Y, Liang Y, Fontenot JD, Rudensky AY. An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoires. Nat Immunol 2006 7 : 401 10.
59. Pacholczyk R, Kern J, Singh N, Iwashima M, Kraj P, Ignatowicz L. Nonself-antigens are the cognate specificities of Foxp3+ regulatory T cells. Immunity 2007 27 : 493 504.
60. Kasow KA, Chen X, Knowles J, Wichlan D, Handgretinger R, Riberdy JM. Human CD4+CD25+ regulatory T cells share equally complex and comparable repertoires with CD4+CD25- counterparts. J Immunol 2004 172 : 6123 8.
61. Fujishima M, Hirokawa M, Fujishima N, Sawada K. TCRalphabeta repertoire diversity of human naturally occurring CD4+CD25+ regulatory T cells. Immunol Lett 2005 99 : 193 7.
62. Arstila TP, Casrouge A, Baron V, Even J, Kanellopoulos J, Kourilsky P. A direct estimate of the human alphabeta T cell receptor diversity. Science 1999 286 : 958 61.
63. Casrouge A, Beaudoing E, Dalle S, Pannetier C, Kanellopoulos J, Kourilsky P. Size estimate of the alpha beta TCR repertoire of naive mouse splenocytes. J Immunol 2000 164 : 5782 7.
64. Pannetier C, Cochet M, Darche S, Casrouge A, Zoller M, Kourilsky P. The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. Proc Natl Acad Sci USA 1993 90 : 4319 23.
65. Miqueu P, Guillet M, Degauque N, Dore JC, Soulillou JP, Brouard S. Statistical analysis of CDR3 length distributions for the assessment of T and B cell repertoire biases. Mol Immunol 2006 44 : 1057 64.
66. Pacholczyk R, Ignatowicz H, Kraj P, Ignatowicz L. Origin and T cell receptor diversity of Foxp3+CD4+CD25+ T cells. Immunity 2006 25 : 249 59.
67. Wong J, Obst R, Correia-Neves M, Losyev G, Mathis D, Benoist C. Adaptation of TCR repertoires to self-peptides in regulatory and nonregulatory CD4+ T cells. J Immunol 2007 178 : 7032 41.
68. Huseby ES, Kappler JW, Marrack P. Thymic selection stifles TCR reactivity with the main chain structure of MHC and forces interactions with the peptide side chains. Mol Immunol 2008 45 : 599 606.
69. Malek TR, Porter BO, Codias EK, Scibelli P, Yu A. Normal lymphoid homeostasis and lack of lethal autoimmunity in mice containing mature T cells with severely impaired IL-2 receptors. J Immunol 2000 164 : 2905 14.
70. Malek TR, Yu A, Vincek V, Scibelli P, Kong L. CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity 2002 17 : 167 78.
71. Tang Q, Henriksen KJ, Boden EK et al. Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells. J Immunol 2003 171 : 3348 52.
72. Tai X, Cowan M, Feigenbaum L, Singer A. CD28 costimulation of developing thymocytes induces Foxp3 expression and regulatory T cell differentiation independently of interleukin 2. Nat Immunol 2005 6 : 152 62.
73. Sakaguchi S. Naturally arising Foxp3-expressing CD25+CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 2005 6 : 345 52.
74. Modigliani Y, Coutinho A, Pereira P, Le Douarin N, Thomas-Vaslin V, Burlen-Defranoux O, Salaun J, Bandeira A. Establishment of tissue-specific tolerance is driven by regulatory T cells selected by thymic epithelium. Eur J Immunol 1996 26 : 1807 15.
75. Papiernik M, de Moraes ML, Pontoux C, Vasseur F, Penit C. Regulatory CD4 T cells: expression of IL-2R alpha chain, resistance to clonal deletion and IL-2 dependency. Int Immunol 1998 10 : 371 8.
76. Scherer MT, Ignatowicz L, Winslow GM, Kappler JW, Marrack P. Superantigens: bacterial and viral proteins that manipulate the immune system. Annu Rev Cell Biol 1993 9 : 101 28.
77. Moore NC, Anderson G, McLoughlin DE, Owen JJ, Jenkinson EJ. Differential expression of Mtv loci in MHC class II-positive thymic stromal cells. J Immunol 1994 152 : 4826 31.
78. Bensinger SJ, Bandeira A, Jordan MS, Caton AJ, Laufer TM. Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4(+)25(+) immunoregulatory T cells. J Exp Med 2001 194 : 427 38.
79. Ribot J, Romagnoli P, van Meerwijk JP. Agonist ligands expressed by thymic epithelium enhance positive selection of regulatory T lymphocytes from precursors with a normally diverse TCR repertoire. J Immunol 2006 177 : 1101 7.
80. Ribot J, Enault G, Pilipenko S, Huchenq A, Calise M, Hudrisier D, Romagnoli P, van Meerwijk JP. Shaping of the autoreactive regulatory T cell repertoire by thymic cortical positive selection. J Immunol 2007 179 : 6741 8.
81. Kurobe H, Liu C, Ueno T et al. CCR7-dependent cortex-to-medulla migration of positively selected thymocytes is essential for establishing central tolerance. Immunity 2006 24 : 165 77.
82. Fontenot JD, Dooley JL, Farr AG, Rudensky AY. Developmental regulation of Foxp3 expression during ontogeny. J Exp Med 2005 202 : 901 6.
83. Watanabe N, Wang YH, Lee HK, Ito T, Wang YH, Cao W, Liu YJ. Hassall's corpuscles instruct dendritic cells to induce CD4+CD25+ regulatory T cells in human thymus. Nature 2005 436 : 1181 5.
84. Aschenbrenner K, D'Cruz LM, Vollmann EH, Hinterberger M, Emmerich J, Swee LK, Rolink A, Klein L. Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells. Nat Immunol 2007 8 : 351 8.
85. Gray D, Abramson J, Benoist C, Mathis D. Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire. J Exp Med 2007 204 : 2521 8.
86. Anderson MS, Venanzi ES, Chen Z, Berzins SP, Benoist C, Mathis D. The cellular mechanism of Aire control of T cell tolerance. Immunity 2005 23 : 227 39.
87. Burchill MA, Yang J, Vang KB et al. Linked T cell receptor and cytokine signaling govern the development of the regulatory T cell repertoire. Immunity 2008 28 : 112 21.
88. Lio CWJ, Hsieh CS. A two-step process for thymic regulatory T cell development. Immunity 2008 28 : 100 11.
89. Liston A, Nutsch KM, Farr AG, Lund JM, Rasmussen JP, Koni PA, Rudensky AY. Differentiation of regulatory Foxp3+ T cells in the thymic cortex. Proc Natl Acad Sci USA 2008 105 : 11903 8.
90. Stephens GL, Andersson J, Shevach EM. Distinct subsets of FoxP3+ regulatory T cells participate in the control of immune responses. J Immunol 2007 178 : 6901 11.
91. Liston A, Rudensky AY. Thymic development and peripheral homeostasis of regulatory T cells. Curr Opin Immunol 2007 19 : 176 85.
92. Stefanova I, Dorfman JR, Germain RN. Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes. Nature 2002 420 : 429 34.
93. Andersson J, Stefanova I, Stephens GL, Shevach EM. CD4+CD25+ regulatory T cells are activated in vivo by recognition of self. Int Immunol 2007 19 : 557 66.
94. Sprent J, Cho JH. Self/non-self discrimination and the problem of keeping T cells alive. Immunol Cell Biol 2008 86 : 54 6.
95. Smith KA. The quantal theory of how the immune system discriminates between "self and non-self". Med Immunol 2004 3 : 3.
96. Pennington DJ, Silva-Santos B, Silberzahn T et al. Early events in the thymus affect the balance of effector and regulatory T cells. Nature 2006 444 : 1073 7.
97. Lin W, Haribhai D, Relland LM, Truong N, Carlson MR, Williams CB, Chatila TA. Regulatory T cell development in the absence of functional Foxp3. Nat Immunol 2007 8 : 359 68.
98. Tuovinen H, Kekalainen E, Rossi LH, Puntila J, Arstila TP. Cutting edge: human CD4-CD8- thymocytes express FOXP3 in the absence of a TCR. J Immunol 2008 180 : 3651 4.
99. Spence PJ, Green EA. Foxp3+ regulatory T cells promiscuously accept thymic signals critical for their development. Proc Natl Acad Sci USA 2008 105 : 973 8.