A well adapted regulatory contrivance: Regulatory T cell development and the forkhead family transcription factor Foxp3

Nature Immunology

Volumn 6, Issue 4, 2005, Pages 331-337

  Fontenot, Jason D ^a   Rudensky, Alexander Y ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; LYMPHOCYTE ANTIGEN RECEPTOR; T LYMPHOCYTE RECEPTOR; TRANSCRIPTION FACTOR FOXP3; DNA BINDING PROTEIN; FORKHEAD TRANSCRIPTION FACTOR; FOXP3 PROTEIN, HUMAN; FOXP3 PROTEIN, MOUSE; LEUKOCYTE ANTIGEN;

AUTOIMMUNITY; CELL LINEAGE; CELL MATURATION; GENETIC ANALYSIS; HUMAN; IMMUNOLOGICAL TOLERANCE; LYMPHOPROLIFERATIVE DISEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; T LYMPHOCYTE; ANIMAL; IMMUNOLOGY; MOUSE; THYMUS;

ANIMALS; ANTIGENS, CD; DNA-BINDING PROTEINS; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; MICE; RECEPTORS, ANTIGEN, T-CELL; SELF TOLERANCE; T-LYMPHOCYTES; THYMUS GLAND;

EID: 16844363097     PISSN: 15292908     EISSN: 15292916     Source Type: Journal    
DOI: 10.1038/ni1179     Document Type: Review

References (93)

1. Ehrlich, P. Collected Studies on Immunity (J. Wiley & Sons, New York, 1910).
2. Burnet, F.M. A modification of Jerne's theory of antibody production using the concept of clonal selection. Australian J. Sci. 20, 67-69 (1957).
3. Talmage, D.W. Allergy and immunology. Annu. Rev. Med. 8, 239-256 (1957).
4. Gershon, R.K. & Kondo, K. Infectious immunological tolerance. Immunology 21, 903-914 (1971).
5. Dorf, M.E. & Benacerraf, B. Suppressor cells and immunoregulation. Annu. Rev. Immunol. 2, 127-157 (1984).
6. Moller, G. Do suppressor T cells exist? Scand. J. Immunol. 27, 247-250 (1988).
7. Nishizuka, Y. & Sakakura, T. Thymus and reproduction: sex-linked dysgenesia of the gonad after neonatal thymectomy in mice. Science 166, 753-755 (1969).
8. + regulatory T cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol. 22, 531-562 (2004).
9. Shevach, E.M. Regulatory T cells in autoimmmunity*. Annu. Rev. Immunol. 18, 423-449 (2000).
10. Sakaguchi, S., Sakaguchi, N., Asano, M., Itoh, M. & Toda, M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor α-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 155, 1151-1164 (1995).
11. Seddon, B. & Mason, D. The third function of the thymus, Immunol. Today 21, 95-99 (2000).
12. + immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J. Exp. Med. 188, 287-296 (1998).
13. + naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int. Immunol. 10, 1969-1980 (1998).
14. + T cells: a population of T cells with immune regulatory activities in vitro. Eur. J. Immunol. 28, 3435-3447 (1998).
15. + regulatory T cells in the steady state. J. Exp. Med. 198, 737-746 (2003).
16. + suppressor T cells in vivo. Nat. Immunol. 3, 33-41 (2002).
17. 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 100, 8886-8891 (2003).
18. + regulatory T cells in vivo. J. Exp. Med. 198, 249-258 (2003).
19. + T cells regulate the expansion of peripheral CD4 T cells through the production of IL-10. J. Immunol. 166, 3008-3018 (2001).
20. Malek, T.R., Yu, A., Vincek, V., Scibelli, P. & Kong, L. CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rβ-deficient mice. Implications for the nonredundant function of IL-2. Immunity 17, 167-178 (2002).
21. + regulatory T cells. Nat. Immunol. 4, 330-336 (2003).
22. Tang, Q. et al. In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J. Exp. Med. 199, 1455-1465 (2004).
23. von Boehmer, H. Mechanisms of suppression by suppressor T cells. Nat. Immunol. 6, 338-344 (2005).
24. + suppressor T cells: more questions than answers. Nat. Rev. Immunol. 2, 389-400 (2002).
25. + T cells through TGF-β-TGF-β receptor interactions in type 1 diabetes. Proc. Natl. Acad. Sci. USA 100, 10878-10883 (2003).
26. Asseman, C., Mauze, S., Leach, M.W., Coffman, R.L. & Powrie, F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J. Exp. Med. 190, 995-1004 (1999).
27. Paust, S., Lu, L., McCarty, N. & Cantor, H. Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc. Natl. Acad. Sci. USA 101, 10398-10403 (2004).
28. + regulatory T cells can mediate suppressor function in the absence of transforming growth factor β1 production and responsiveness. J. Exp. Med. 196, 237-246 (2002).
29. + regulatory T cell function. Eur. J. Immunol. 34, 2996-3005 (2004).
30. Grossman, W.J. et al. Human T regulatory cells can use the perform pathway to cause autologous target cell death. Immunity 21, 589-601 (2004).
31. Barthlott, T., Kassiotis, G. & Stockinger, B. T cell regulation as a side effect of homeostasis and competition. J. Exp. Med. 197, 451-460 (2003).
32. + Treg cells: highly potent regulators of diabetes that require TRANCE-RANK signals. Immunity 16, 183-191 (2002).
33. + T cell suppressor function. J. Immunol. 172, 6519-6523 (2004).
34. + regulatory T cell function. Eur. J. Immunol. 34, 2480-2488 (2004).
35. + regulatory T cells by peripheral expansion. J. Immunol. 173, 7259-7268 (2004).
36. + and CD25- subpopulations. J. Immunol. 165, 3105-3110 (2000).
37. + naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J. Immunol. 162, 5317-5326 (1999).
38. Papiernik, M., de Moraes, M.L., Pontoux, C., Vasseur, F. & Penit, C. Regulatory CD4 T cells: expression of IL-2Rα chain, resistance to clonal deletion and IL-2 dependency. Int. Immunol. 10, 371-378 (1998).
39. + regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 3, 135-142 (2002).
40. Asano, M., Toda, M., Sakaguchi, N. & Sakaguchi, S. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J. Exp. Med. 184, 387-396 (1996).
41. + T cells. Proc. Natl. Acad. Sci. USA 101, 14473-14478 (2004).
42. Goldrath, A.W. & Bevan, M.J. Selecting and maintaining a diverse T-cell repertoire. Nature 402, 255-262 (1999).
43. + regulatory T cells. Curr. Opin. Immunol. 16, 203-208 (2004).
44. + regulatory T cell biology. Curr. Top. Microbiol. Immunol. (in the press).
45. Lafaille, J.J., Nagashima, K., Katsuki, M. & Tonegawa, S. High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic mice. Cell 78, 399-408 (1994).
46. + T cells expressing endogenous T cell receptor chains protect myelin basic protein-specific transgenic mice from spontaneous autoimmune encephalomyelitis. J. Exp. Med. 188, 1883-1894 (1998).
47. + 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. 168, 4399-4405 (2002).
48. + regulatory T cells induced by an agonist self-peptide. Nat. Immunol. 2, 301-306 (2001).
49. Apostolou, I., Sarukhan, A., Klein, L. & von Boehmer, H. Origin of regulatory T cells with known specificity for antigen. Nat. Immunol. 3, 756-763 (2002).
50. + immunoregulatory T cells: gene expression analysis reveals a functional role for the glucocorticoid-induced TNF receptor. Immunity 16, 311-323 (2002).
51. + regulatory and natural killer-like T cells on signals leading to NF-κB activation. Proc. Natl. Acad. Sci. USA 101, 4566-4571 (2004).
52. Schmidt-Supprian, M. et al. Mature T cells depend on signaling through the IKK complex. Immunity 19, 377-389 (2003).
53. + T cell receptors. Immunity 21, 267-277 (2004).
54. Hernandez-Hoyos, G., Sohn, S.J., Rothenberg, E.V. & Alberola-Ila, J. Lck activity controls CD4/CD8 T cell lineage commitment. Immunity 12, 313-322 (2000).
55. + T cells. Immunity 13, 59-71 (2000).
56. van Santen, H.M., 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. 200, 1221-1230 (2004).
57. Viret, C. & Janeway, C.A., Jr. Self-specific MHC class II-restricted CD4-CD8- T cells that escape deletion and lack regulatory activity. J. Immunol. 170, 201-209 (2003).
58. Modigliani, Y. et al. Lymphocytes selected in allogeneic thymic epithelium mediate dominant tolerance toward tissue grafts of the thymic epithelium haplotype. Proc. Natl. Acad. Sci. USA 92, 7555-7559 (1995).
59. Modigliani, Y. et al. Establishment of tissue-specific tolerance is driven by regulatory T cells selected by thymic epithelium. Eur. J. Immunol. 26, 1807-1815 (1996).
60. + immunoregulatory T cells. J. Exp. Med. 194, 427-438 (2001).
61. + T cells. J. Immunol. 168, 613-620 (2002).
62. Kyewski, B. & Derbinski, J. Self-representation in the thymus: an extended view. Nat. Rev. Immunol. 4, 688-698 (2004).
63. + immunoregulatory T cells that control autoimmune diabetes. Immunity 12, 431-440 (2000).
64. 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. 6, 152-162 (2005).
65. +CD25- T cells through Foxp3 induction and down-regulation of Smad7. J. Immunol. 172, 5149-5153 (2004).
66. + cells educate CD4+CD25- cells to develop suppressive activity: the role of IL-2, TGF-β, and IL-10. J. Immunol. 172, 5213-5221 (2004).
67. + regulatory T cells by TGF-β induction of transcription factor Foxp3. J. Exp. Med. 198, 1875-1886 (2003).
68. +CD25- T cells. Int. Immunol. 16, 1203-1213 (2004).
69. + T-cell pool and the expression of Foxp3 in vivo. Int. Immunol. 16, 1241-1249 (2004).
70. + T cells. J. Immunol. 173, 6526-6531 (2004).
71. Malek, T.R. & Bayer, A.L. Tolerance, not immunity, crucially depends on IL-2. Nat. Rev. Immunol. 4, 665-674 (2004).
72. + regulatory T cell function. J. Exp. Med. 196, 851-857 (2002).
73. Stockinger, B., Barthlott, T. & Kassiotis, G. T cell regulation: a special job or everyone's responsibility? Nat. Immunol. 2, 757-758 (2001).
74. Brunkow, M.E. et al. Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliterative disorder of the scurfy mouse. Nat. Genet. 27, 68-73 (2001).
75. Chatila, T.A. et al. JM2, encoding a fork head-related protein, is mutated in X-linked autoimmunity-allergic disregulation syndrome. J, Clin. Invest. 106, R75-R81 (2000).
76. 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).
77. 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).
78. + regulatory T cells in immunologic tolerance to self and non-self. Nat. Immunol. 6, 345-352 (2005).
79. Gambineri, E., Torgerson, T.R. & Ochs, H.D. Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis. Curr. Opin. Rheumatol. 15, 430-435 (2003).
80. Godfrey, V.L., Wilkinson, J.E. & Russell, L.B. X-linked lymphoreticular disease in the scurfy (sf) mutant mouse. Am. J. Pathol. 138, 1379-1387 (1991).
81. Godfrey, V.L., Rouse, B.T. & Wilkinson, J.E. Transplantation of T cell-mediated, lympho-reticular disease from the scurfy (sf) mouse. Am. J. Pathol. 145, 281-286 (1994).
82. Godfrey, V.L., Wilkinson, J.E., Rinchik, E.M. & Russell, L.B. Fatal lymphoreticular disease in the scurfy (sf) mouse requires T cells that mature in a sf thymic environment: potential model for thymic education. Proc. Natl. Acad. Sci. USA 88, 5528-5532 (1991).
83. - T cells are the effector cells in disease pathogenesis in the scurfy (sf) mouse. J. Immunol. 153, 3764-3774 (1994).
84. Clark, L.B. et al. Cellular and molecular characterization of the scurfy mouse mutant. J. Immunol. 162, 2546-2554 (1999).
85. Kanangat, S. et al. Disease in the scurfy (sf) mouse is associated with overexpression of cytokine genes. Eur. J. Immunol. 26, 161-165 (1996).
86. Khattri, R. et al. The amount of scurfin protein determines peripheral T cell number and responsiveness. J. Immunol. 167, 6312-6320 (2001).
87. Kaestner, K.H., Knöchel, W. & Martinez, D.E. Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev. 14, 142-146 (2000).
88. Schubert, L.A., Jeffery, E., Zhang, Y., Ramsdell, F. & Ziegler, S.F. Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J. Biol. Chem. 276, 37672-37679 (2001).
89. + T regulatory cells. Nat. Immunol. 4, 337-342 (2003).
90. Hori, S., Nomura, T. & Sakaguchi, S. Control of regulatory T cell development by the transcription factor Foxp3. Science 299, 1057-1061 (2003).
91. Fontenot, J.D. et al. Regulatory T cell lineage specification by the forkhead transcription factor Foxp3. Immunity (in the press).
92. +CD25- T cells. J. Clin. Invest. 112, 1437-1443 (2003).
93. + regulatory T cells. Int. Immunol. 16, 1643-1656 (2004).