Induction and maintenance of self tolerance: The role of CD4 +CD25+ regulatory T cells

Archivum Immunologiae et Therapiae Experimentalis

Volumn 54, Issue 5, 2006, Pages 307-321

  Bala, Kamalesh K ^a   Moudgil, Kamal D ^a  

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

Author keywords

Autoimmunity; CD4+CD25+ T cells; Regulatory T cells; Tolerance

Indexed keywords

AUTOIMMUNE REGULATOR PROTEIN; TRANSCRIPTION FACTOR FOXP3;

ADOPTIVE IMMUNOTHERAPY; ANTIGEN SPECIFICITY; AUTOIMMUNITY; CD4+ CD25+ T LYMPHOCYTE; CELL ACTIVITY; CELL CONTACT; CELL DEATH; CELL FUNCTION; CELL SURFACE; CLONAL ANERGY; ENTEROPATHY; GENE MUTATION; HUMAN; IMMUNE DYSREGULATION; IMMUNE SYSTEM; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; NONHUMAN; POLYENDOCRINOPATHY; PROTEIN EXPRESSION; REGULATORY T LYMPHOCYTE; REVIEW; X CHROMOSOME LINKED DISORDER;

ANIMALS; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT; MICE; SELF TOLERANCE; T-LYMPHOCYTES, REGULATORY;

EID: 33750366461     PISSN: 0004069X     EISSN: 16614917     Source Type: Journal    
DOI: 10.1007/s00005-006-0035-x     Document Type: Review

References (214)

1. Adler A. J., Marsh D. W., Yochum G. S., Guzzo J. L., Nigam A, Nelson W. G. and Pardoll D. M. (1998): CD4+ T cell tolerance to parenchymal self-antigens requires presentation by bone marrow-derived antigen-presenting cells. J. Exp. Med., 187, 1555-1564.
2. Albert M. H., Anasetti C. and Yu X. Z. (2006): T regulatory cells as an immunotherapy for transplantation. Expert Opin. Biol. Ther., 6, 315-324.
3. Alferink J., Tafuri A., Vestweber D., Hallmann R., Hammerling G. J. and Arnold B. (1998): Control of neonatal tolerance to tissue antigens by peripheral T cell trafficking. Science, 282, 1338-1341.
4. Allen S., Read S., DiPaolo R., McHugh R. S., Shevach E. M., Gleeson P. A. and van Driel I. R. (2005): Promiscuous thymic expression of an autoantigen gene does not result in negative selection of pathogenic T cells. J. Immunol., 175, 5759-5764.
5. Anderson A. C., Nicholson L. B., Legge K. L., Turchin V., Zaghouani H. and Kuchroo V. K. (2000): High frequency of autoreactive myelin proteolipid protein-specific T cells in the periphery of naive mice: mechanisms of selection of the self-reactive repertoire. J. Exp. Med., 191, 761-760.
6. Anderson M. S., Venanzi E. S., Chen Z., Berzins S. P., Benoist C. and Mathis D. (2005): The cellular mechanism of Aire control of T cell tolerance. Immunity, 23, 227-239.
7. Anderson M. S., Venanzi E. S., Klein L., Chen Z., Berzins S. P., Turley S. J., von Boehmer H., Bronson R., Dierich A., Benoist C. and Mathis D. (2002): Projection of an immunological self shadow within the thymus by the aire protein. Science, 298, 1395-1401.
8. Anderson M. S. (2002): Autoimmune endocrine disease. Curr. Opin. Immunol., 14, 760-764.
9. Anderton S. M., Radu C. G., Lowrey P. A., Ward E. S. and Wraith D. C. (2001): Negative selection during the peripheral immune response to antigen. J. Exp. Med., 193, 1-11.
10. Annunziato F., Cosmi L., Liotta F., Lazzeri E., Manetti R., Vanini V., Romagnani P., Maggi E. and Romagnani S. (2002): Phenotype, localization, and mechanism of suppression of CD4(+)CD25(+) human thymocytes. J. Exp. Med., 196, 379-387.
11. Ansel K. M., Lee D. U. and Rao A. (2003): An epigenetic view of helper T cell differentiation. Nat. Immunol., 4, 616-623.
12. Apostolou I., Sarukhan A., Klein L. and von Boehmer H. (2002): Origin of regulatory T cells with known specificity for antigen. Nat. Immunol., 3, 756-763.
13. Apostolou I. and von Boehmer H. (2004): In vivo instruction of suppressor commitment in naive T cells. J. Exp. Med., 199, 1401-1408.
14. Asano M., Toda M., Sakaguchi N. and Sakaguchi S. (1996): Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J. Exp. Med., 184, 387-396.
15. Ashton-Rickardt P. G., Van Kaer L., Schumacher T. N., Ploegh H. L. and Tonegawa S. (1993): Peptide contributes to the specificity of positive selection of CD8+ T cells in the thymus. Cell, 73, 1041-1049.
16. Avichezer D., Grajewski R. S., Chan C. C., Mattapallil M. J., Silver P. B., Raber J. A., Liou G. I., Wiggert B., Lewis G. M., Donoso L. A. and Caspi R. R. (2003): An immunologically privileged retinal antigen elicits tolerance: major role for central selection mechanisms. J. Exp. Med., 198, 1665-1676.
17. Bacchetta R., Gregori S. and Roncarolo M. G. (2005): CD4+ regulatory T cells: mechanisms of induction and effector function. Autoimmun. Rev., 4, 491-496.
18. Bach J. F. (2003): Regulatory T cells under scrutiny. Nat. Rev. Immunol., 3, 189-198.
19. Bachmann M. F., Kohler G., Ecabert B., Mak T. W. and Kopf M. (999): utting edge: lymphoproliferative disease in the absence of CTLA-4 is not T cell autonomous. J. Immunol., 163, 1128-1131.
20. Baecher-Allan C. and Hafler D. A. (2004): Suppressor T cells in human diseases. J. Exp. Med., 200, 273-276.
21. Basu S., Binder R. J., Suto R., Anderson K. M. and Srivastava P. K. (2000): Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int. Immunol., 12, 1539-1546.
22. Belkaid Y., Piccirillo C. A., Mendez S., Shevach E. M. and Sacks D. L. (2002): CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature, 420, 502-507.
23. Bensinger S. J., Bandeira A., Jordan M. S., Caton A. J. and Laufer T. M. (2001): Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4(+)25(+) immunoregulatory T cells. J. Exp. Med., 194, 427-448.
24. Bjorses P., Halonen M., Palvimo J. J., Kolmer M., Aaltonen J., Ellonen P., Perheentupa J., Ulmanen I. and Peltonen L. (2000): Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein. Am. J. Hum. Genet., 66, 378-392.
25. Bluestone J. A. and Abbas A. K. (2003): Natural versus adaptive regulatory T cells. Nat. Rev. Immunol., 3, 253-257.
26. Bluestone J. A. and Tang Q. (2004): Therapeutic vaccination using CD4+CD25+ antigen-specific regulatory T cells. Proc. Natl. Acad. Sci. USA, 101 (suppl. 2), 14622-14626.
27. Bouneaud C., Kourilsky P. and Bousso P. (2000): Impact of negative selection on the T cell repertoire reactive to a self-peptide: a large fraction of T cell clones escapes clonal deletion. Immunity, 13, 829-840.
28. Brandle D., Muller S., Muller C., Hengartner H. and Pircher H. (1994): Regulation of RAG-1 and CD69 expression in the thymus during positive and negative selection. Eur. J. Immunol., 24, 145-151.
29. Brennan P. J., Saouaf S. J., Greene M. I. and Shen Y. (2003): Anergy and suppression as coexistent mechanisms for the maintenance of peripheral T cell tolerance. Immunol. Res., 2, 295-302.
30. Chakraborty N. G., Chattopadhyay S., Mehrotra S., Chhabra A. and Mukherji B. (2004): Regulatory T-cell response and tumor vaccine-induced cytotoxic T lymphocytes in human melanoma. Hum. Immunol., 65, 794-802.
31. Charles P. C., Weber K. S., Cipriani B. and Brosnan C. F. (1999): Cytokine, chemokine and chemokine receptor mRNA expression in different strains of normal mice: implications for establishment of a Th1/Th2 bias. J. Neuroimmunol., 100, 64-73.
32. Chen W., Jin W., Hardegen N., Lei K. J., Li L., Marinos N., McGrady G. and Wahl S. M. (2003): Conversion of peripheral CD4+CD25- naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J. Exp. Med., 198, 1875-1886.
33. Cibotti R., Kanellopoulos J. M., Cabaniols J. P., Halle-Panenko O., Kosmatopoulos K., Sercarz E. and Kourilsky P. (1992): Tolerance to a self-protein involves its immunodominant but does not involve its subdominant determinants. Proc. Natl. Acad. Sci. USA, 89, 416-420.
34. Cobbold S. P., Castejon R., Adams E., Zelenika D., Graca L., Humm S. and Waldmann H. (2004): Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants. J. Immunol., 172, 6003-6010.
35. Coutinho A., Hori S., Carvalho T., Caramalho I. and Demengeot J. (2001): Regulatory T cells: the physiology of autoreactivity in dominant tolerance and "quality control" of immune responses. Immunol. Rev., 182, 89-98.
36. Curiel T. J., Coukos G., Zou L., Alvarez X., Cheng P., Mottram P., Evdemon-Hogan M., Conejo-Garcia J. R., Zhang L., Burow M., Zhu Y., Wei S., Kryczek I., Daniel B., Gordon A., Myers L., Lackner A., Disis M. L., Knutson K. L., Chen L. and Zou W. (2004): Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat. Med., 10, 942-949.
37. Curotto de Lafaille M. A., Lino A. C., Kutchukhidze N. and Lafaille J. J. (2004): CD25- T cells generate CD25+Foxp3+ regulatory T cells by peripheral expansion. J. Immunol., 173, 7259-7268.
38. Dai Z., Li Q., Wang Y., Gao G., Diggs L. S., Tellides G. and Lakkis F. G. (2004): CD4+CD25+ regulatory T cells suppress allograft rejection mediated by memory CD8+ T cells via a CD30-dependent mechanism. J. Clin. Invest., 113, 310-317.
39. Darrasse-Jeze G., Klatzmann D., Charlotte F., Salomon B. L. and Cohen J. L. (2006): CD4+CD25+ regulatory/suppressor T cells prevent allogeneic fetus rejection in mice. Immunol. Lett., 102, 106-109.
40. Delarasse C., Daubas P., Mars L. T., Vizler C, Litzenburger T., Iglesias A., Bauer J., Della Gaspera B., Schubart A., Decker L., Dimitri D., Roussel G., Dierich A., Amor S., Dautigny A., Liblau R. and Pham-Dinh D. (2003): Myelin/oligodendrocyte glycoprotein-deficient (MOG-deficient) mice reveal lack of immune tolerance to MOG in wild-type mice. J. Clin. Invest., 112, 544-553.
41. Derbinski J., Schulte A, Kyewski B. and Klein L. (2001): Promiscuous gene expression in medullary thymic epithelial cells mirrors the peripheral self. Nat. Immunol., 2, 1032-1039.
42. Durai M., Gupta R. S. and Moudgil K. D. (2004): The T cells specific for the carboxyl-terminal determinants of self (rat) heat-shock protein 65 escape tolerance induction and are involved in regulation of autoimmune arthritis. J. Immunol., 172, 2795-2802.
43. Durai M., Kim H. R. and Moudgil K. D. (2004): The regulatory C-terminal determinants within mycobacterial heat shock protein 65 are cryptic and cross-reactive with the dominant self homologs: implications for the pathogenesis of autoimmune arthritis. J. Immunol., 173, 181-188.
44. Faideau B., Briand J. P., Lotton C., Tardivel I., Halbout P., Jami J., Elliott J. F., Krief P., Muller S., Boitard C. and Carel J. C. (2004): Expression of preproinsulin-2 gene shapes the immune response to preproinsulin in normal mice. J. Immunol., 172, 25-33.
45. Faria A. M. and Weiner H. L. (2005): Oral tolerance. Immunol. Rev., 206, 232-259.
46. Fehervari Z. and Sakaguchi S. (2004): Development and function of CD25+CD4+ regulatory T cells. Curr. Opin. Immunol., 16, 203-208.
47. Fisher G. H., Rosenberg F. J., Straus S. E., Dale J. K., Middleton L. A., Lin A. Y., Strober W., Lenardo M. J. and Puck J. M. (1995): Dominant interfering Fas gene mutations impair apoptosis in a human autoimmune lymphoproliferative syndrome. Cell, 81, 935-946.
48. Fisson S., Darrasse-Jeze G., Litvinova E., Septier F., Klatzmann D., Liblau R. and Salomon L. (2003): Continuous activation of autoreactive CD4+CD25+ regulatory T cells in the steady state. J. Exp. Med., 198, 737-746.
49. Fisson S., Djelti F., Trenado A., Billiard F., Liblau R., Klatzmann D., Cohen J. L. and Salomon B. L. (2006): Therapeutic potential of self-antigen-specific CD4(+)CD25(+) regulatory T cells selected in vitro from a polyclonal repertoire. Eur. J. Immunol., 36, 817-827.
50. Fontenot J. D., Gavin M. A. and Rudensky A. Y. (2003): Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat. Immunol., 4, 330-336.
51. Fontenot J. D. and Rudensky A. Y. (2005): A well adapted regulatory contrivance: regulatory T cell development and the forkhead family transcription factor Foxp3. Nat. Immunol., 6, 331-337.
52. Fukaura H., Kent S. C., Pietrusewicz M. J., Khoury S. J., Weiner H. L. and Hafler D. A. (1996): Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. J. Clin. Invest., 98, 70-77.
53. Furtado G. C., Olivares-Villagomez D., Curotto de Lafaille M. A., Wensky A. K., Latkowski J. A. and Lafaille J. J. (2001): Regulatory T cells in spontaneous autoimmune encephalomyelitis. Immunol. Rev., 182, 122-134.
54. Gambineri E., Torgerson T. R. and Ochs H. D. (2003): 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.
55. Gammon G. and Sercarz E. (1989): How some T cells escape tolerance induction. Nature, 342, 183-185.
56. Germain R. N. (2002): T-cell development and the CD4-CD8 lineage decision. Nat. Rev. Immunol., 2, 309-322.
57. Ghiringhelli F., Menard C., Terme M., Flament C., Taieb J., Chaput N., Puig P. E., Novault S., Escudier B., Vivier E., Lecesne A., Robert C., Blay J. Y., Bernard J., Caillat-Zucman S., Freitas A., Tursz T., Wagner-Ballon O., Capron C., Vainchencker W., Martin F. and Zitvogel L. (2005): CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J. Exp. Med., 202, 1075-1085.
58. Godfrey V. L., Wilkinson J. E. and Russell L. B. (1991): X-linked lymphoreticular disease in the scurfy (sf) mutant mouse. Am. J. Pathol., 138, 1379-1387.
59. Gondek D. C., Lu L. F., Quezada S. A., Sakaguchi S. and Noelle R. J. (2005): Cutting edge: Contact-mediated suppression by CD4+CD25+ regulatory cells involves a granzyme b-dependent, perforin-independent mechanism. J. Immunol., 174, 1783-1786.
60. Gregori S., Giarratana N., Smiroldo S. and Adorini L. (2003): Dynamics of pathogenic and suppressor T cells in autoimmune diabetes development. J. Immunol., 171, 4040-4047.
61. Grewal I. S., Moudgil K. D. and Sercarz E. E. (1995): Hindrance of binding to class II major histocompatibility complex molecules by a single amino acid residue contiguous to a determinant leads to crypticity of the determinant as well as lack of response to the protein antigen. Proc. Natl. Acad. Sci. USA, 92, 1779-1783.
62. Grossman W. J., Verbsky J. W., Barchet W., Colonna M., Atkinson J. P. and Ley T. J. (2004): Human T regulatory cells can use the perforin pathway to cause autologous target cell death. Immunity, 21, 589-601.
63. Groux H., O'Garra A., Bigler M., Rouleau M., Antonenko S., de Vries J. E. and Roncarolo M. G. (1997): A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature, 389, 737-742.
64. Grundstrom S., Cederbom L., Sundstedt A., Scheipers P. and Ivars F. (2003): Superantigen-induced regulatory T cells display different suppressive functions in the presence or absence of natural CD4+CD25+ regulatory T cells in vivo. J. Immunol., 170, 5008-5017.
65. Hogquist K. A., Gavin M. A. and Bevan M. J. (1993): Positive selection of CD8+ T cells induced by major histocompatibility complex binding peptides in fetal thymic organ culture. J. Exp. Med., 177, 1469-1473.
66. Hori S., Nomura T. and Sakaguchi S. (2003): Control of regulatory T cell development by the transcription factor Foxp3. Science, 299, 1057-1061.
67. Hsieh C. S., Liang Y., Tyznik A. J., Self S. G., Liggitt D. and Rudensky A. Y. (2004): Recognition of the peripheral self by naturally arising CD25+CD4+ T cell receptors. Immunity, 21, 267-277.
68. Huehn J., Siegmund K., Lehmann J. C., Siewert C., Haubold U., Feuerer M., Debes G. F., Lauber J., Frey O., Przybylski G. K., Niesner U., de la Rosa M., Schmidt C. A., Brauer R., Buer J., Scheffold A. and Hamann A. (2004): Developmental stage, phenotype, and migration distinguish naive- and effector/memory-like CD4+ regulatory T cells. J. Exp. Med., 199, 303-313.
69. Hwang E. S., Szabo S. J., Schwartzberg P. L. and Glimcher L. H. (2005): T helper cell fate specified by kinase-mediated interaction of T-bet with GATA-3. Science, 307, 430-433.
70. Ichihara F., Kono K., Takahashi A., Kawaida H., Sugai H. and Fujii H. (2003): Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers. Clin. Cancer Res., 9, 4404-4408.
71. Jenkins M. K. and Schwartz R. H. (1987): Antigen presentation by chemically modified splenocytes induces antigen-specific T cell unresponsiveness in vitro and in vivo. J. Exp. Med., 165, 302-319.
72. Jiang S., Camara N., Lombardi G. and Lechler R. I. (2003): Induction of allopeptide-specific human CD4+CD25+ regulatory T cells ex vivo. Blood, 102, 2180-2186.
73. Joffre O., Gorsse N., Romagnoli P., Hudrisier D. and van Meerwijk J. P. (2004): Induction of antigen-specific tolerance to bone marrow allografts with CD4+CD25+ T lymphocytes. Blood, 103, 4216-4221.
74. Jolicoeur C., Hanahan D. and Smith K. M. (1994): T-cell tolerance toward a transgenic beta-cell antigen and transcription of endogenous pancreatic genes in thymus. Proc. Natl. Acad. Sci. USA, 91, 6707-6711.
75. Jones S. C., Murphy G. F. and Korngold R. (2003): Post-hematopoietic cell transplantation control of graft-versus-host disease by donor CD425 T cells to allow an effective graft-versus-leukemia response. Biol. Blood Marrow Transplant., 9, 243-256.
76. Jonuleit H., Schmitt E., Schuler G., Knop J. and Enk A. H. (2000): Induction of interleukin 10-producing, nonproliferating CD4(+) T cells with regulatory properties by repetitive stimulation with allogeneic immature human dendritic cells. J. Exp. Med., 192, 1213-1222.
77. Kaestner K. H., Knochel W. and Martinez D. E. (2000): Unified nomenclature for the winged helix/forkhead transcription factors. Genes Dev., 14, 142-146.
78. Kang H. K. and Datta S. K. (2006): Regulatory T cells in lupus. Int. Rev. Immunol., 25, 5-25.
79. Kang H. K., Michaels M. A., Berner B. R. and Datta S. K. (2005): Very low-dose tolerance with nucleosomal peptides controls lupus and induces potent regulatory T cell subsets. J. Immunol., 174, 3247-3255.
80. Kappler J. W., Roehm N. and Marrack P. (1987): T cell tolerance by clonal elimination in the thymus. Cell, 49, 273-280.
81. Karim M., Kingsley C. I., Bushell A. R., Sawitzki B. S. and Wood K. J. (2004): Alloantigen-induced CD25+CD4+ regulatory T cells can develop in vivo from CD25-CD4+ precursors in a thymus-independent process. J. Immunol., 172, 923-928.
82. Kawahata K., Misaki Y., Yamauchi M., Tsunekawa S., Setoguchi K., Miyazaki J. and Yamamoto K. (2002): 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., 168, 4399-4405.
83. Khoo U. Y., Proctor I. E. and Macpherson A. J. (1997): CD4+ T cell down-regulation in human intestinal mucosa: evidence for intestinal tolerance to luminal bacterial antigens. J. Immunol., 158, 3626-3634.
84. Kinjo Y., Wu D., Kim G., Xing G. W., Poles M. A., Ho D. D., Tsuji M., Kawahara K., Wong C. H. and Kronenberg M. (2005): Recognition of bacterial glycosphingolipids by natural killer T cells. Nature, 434, 520-525.
85. Kisielow P., Bluthmann H., Staerz U. D., Steinmetz M. and von Boehmer H. (1988): Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes. Nature, 333, 742-746.
86. Klein L., Khazaie K. and von Boehmer H. (2003): In vivo dynamics of antigen-specific regulatory T cells not predicted from behavior in vitro. Proc. Natl. Acad. Sci. USA, 100, 8886-8891.
87. Klein L., Roettinger B. and Kyewski B. (2001): Sampling of complementing self-antigen pools by thymic stromal cells maximizes the scope of central T cell tolerance. Eur. J. Immunol., 31, 2476-2486.
88. Kohm A. P., Carpentier P. A., Anger H. A. and Miller S. D. (2002): Cutting edge: CD4+CD25+ regulatory T cells suppress antigen-specific autoreactive immune responses and central nervous system inflammation during active experimental autoimmune encephalomyelitis. J. Immunol., 169, 4712-4716.
89. Kohm A. P., Carpentier P. A. and Miller S. D. (2003): Regulation of experimental autoimmune encephalomyelitis (EAE) by CD4+CD25+ regulatory T cells. Novartis Found Symp., 252, 45-52; discussion-4, 106-114.
90. Kourilsky P., Chaouat G., Rabourdin-Combe C. and Claverie J. M. (1987): Working principles in the immune system implied by the "peptidic self" model. Proc. Natl. Acad. Sci. USA, 84, 3400-3404.
91. Kurts C., Miller J. F., Subramaniam R. M., Carbone F. R. and Heath W. R. (1998): Major histocompatibility complex class I-restricted cross-presentation is biased towards high dose antigens and those released during cellular destruction. J. Exp. Med., 188, 409-414.
92. Kyewski B. and Derbinski J. (2004): Self-representation in the thymus: an extended view. Nat. Rev. Immunol., 4, 688-698.
93. La Cava A., Ebling F. M. and Hahn B. H. (2004): Ig-reactive CD4+CD25+ T cells from tolerized (New Zealand Black x New Zealand White)F1 mice suppress in vitro production of antibodies to DNA. J. Immunol., 173, 3542-3548.
94. Lan R. Y., Ansari A. A, Lian Z. X. and Gershwin M. E. (2005): Regulatory T cells: development, function and role in autoimmunity. Autoimmun Rev., 4, 351-363.
95. Laufer T. M., DeKoning J., Markowitz J. S., Lo D. and Glimcher L. H. (1996): Unopposed positive selection and autoreactivity in mice expressing class II MHC only on thymic cortex. Nature, 383, 81-85.
96. Lawson C. A., Brown A. K., Bejarano V., Douglas S. H., Burgoyne C. H., Greenstein A. S., Boylston A. W., Emery P., Ponchel F. and Isaacs J. D. (2006): Early rheumatoid arthritis is associated with a deficit in the CD4+CD25high regulatory T cell population in peripheral blood. Rheumatology (in press).
97. Lechner O., Lauber J., Franzke A., Sarukhan A., von Boehmer H. and Buer J. (2001): Fingerprints of anergic T cells. Curr. Biol., 11, 587-595.
98. Lerman M. A., Larkin J. 3rd., Cozzo C., Jordan M. S. and Caton A. J. (2004): CD4+ CD25+ regulatory T cell repertoire formation in response to varying expression of a neo-self-antigen. J. Immunol., 173, 236-244.
99. Levings M. K., Sangregorio R., Sartirana C., Moschin A. L., Battaglia M., Orban P. C. and Roncarolo M. G. (2002): Human CD25+CD4+ T suppressor cell clones produce transforming growth factor beta, but not interleukin 10, and are distinct from type 1 T regulatory cells. J. Exp. Med., 196, 1335-1346.
100. Lim H. W., Hillsamer P., Banham A. H. and Kim C. H. (2005): Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells. J. Immunol., 175, 4180-4183.
101. Lin R. H. and Stockinger B. (1989): T cell immunity or tolerance as a consequence of self antigen presentation. Eur. J. Immunol., 19, 105-110.
102. Liu G. Y., Fairchild P. J., Smith R. M., Prowle J. R., Kioussis D. and Wraith D. C. (1995): Low avidity recognition of self-antigen by T cells permits escape from central tolerance. Immunity, 3, 407-415.
103. Liyanage U. K., Moore T. T., Joo H. G., Tanaka Y., Herrmann V., Doherty G., Drebin J. A., Strasberg S. M., Eberlein T. J., Goedegebuure P. S. and Linehan D. C. (2002): Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J. Immunol., 169, 2756-2761.
104. Lohmann T., Leslie R. D. and Londei M. (1996): T cell clones to epitopes of glutamic acid decarboxylase 65 raised from normal subjects and patients with insulin-dependent diabetes. J. Autoimmun., 9, 385-389.
105. Lorenz R. G. and Allen P. M. (1988): Direct evidence for functional self-protein/Ia-molecule complexes in vivo. Proc. Natl. Acad. Sci. USA, 85, 5220-5223.
106. Mahnke K., Qian Y., Knop J. and Enk A. H. (2003): Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. Blood, 101, 4862-4869
107. Malek T. R., Porter B. O., Codias E. K., Scibelli P. and Yu A. (2000): Normal lymphoid homeostasis and lack of lethal autoimmunity in mice containing mature T cells with severely impaired IL-2 receptors. J. Immunol., 164, 2905-2914.
108. Malek T. R., Yu A., Vincek V., Scibelli P. and Kong L. (2002): CD4 regulatory T cells prevent lethal autoimmunity in IL-2Rbeta-deficient mice. Implications for the nonredundant function of IL-2. Immunity, 17, 167-178.
109. Margalit M. and Ilan Y. (2005): Induction of immune tolerance: a role for natural killer T lymphocytes? Liver Int., 25, 501-504.
110. Masteller E. L., Warner M. R., Tang Q., Tarbell K. V., McDevitt H. and Bluestone J. A. (2005):xpansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice. J. Immunol., 75, 3053-3059.
111. Mathis D. and Benoist C. (2004): Back to central tolerance. Immunity, 20, 509-516.
112. Maverakis E., Beech J., Stevens D. B., Ametani A., Brossay L., van den Elzen P., Mendoza R., Thai Q., Macias L. H., Ethell D., Campagnoni C. W., Campagnoni A. T., Sette A. and Sercarz E. E. (2003): Autoreactive T cells can be protected from tolerance induction through competition by flanking determinants for access to class II MHC. Proc. Natl. Acad. Sci. USA, 100, 5342-5347.
113. McHugh R. S. and Shevach E. M. (2002): Cutting edge: depletion of CD4+CD25+ regulatory T cells is necessary, but not sufficient, for induction of organ-specific autoimmune disease. J. Immunol., 168, 5979-5983.
114. Mekala D. J. and Geiger T. L. (2005): Immunotherapy of autoimmune encephalomyelitis with redirected CD4+ +CD25+ T lymphocytes. Blood, 105, 2090-2092.
115. Mellor A. L. and Munn D. H. (2004): IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat. Rev. Immunol., 4, 762-774.
116. Michaels M. A., Kang H. K., Kaliyaperumal A., Satyaraj E., Shi Y. and Datta S. K. (2005): A defect in deletion of nucleosome-specific autoimmune T cells in lupus-prone thymus: role of thymic dendritic cells. J. Immunol., 175, 5857-5865.
117. Monk C. R., Spachidou M., Rovis F., Leung E., Botto M., Lechler R. I. and Garden O. A. (2005): MRL/Mp CD4+,CD25- T cells show reduced sensitivity to suppression by CD4+,CD25+ regulatory T cells in vitro: a novel defect of T cell regulation in systemic lupus erythematosus. Arthritis Rheum., 52, 1180-1184.
118. Mosmann T. R. and Sad S. (1996): The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol. Today, 17, 138-146.
119. Moudgil K. D. (1998): Diversification of response to hsp65 during the course of autoimmune arthritis is regulatory rather than pathogenic. Immunol. Rev., 164, 175-184.
120. Moudgil K. D. (1999): Determinant hierarchy: shaping of the self-directed T cell repertoire, and induction of autoimmunity. Immunol. Lett., 68, 251-256.
121. Moudgil K. D., Ametani A., Grewal I. S., Kumar V. and Sercarz E. E. (1993): Processing of self-proteins and its impact on shaping the T cell repertoire, autoimmunity and immune regulation. Int. Rev. Immunol., 10, 365-377.
122. Moudgil K. D., Chang T. T., Eradat H., Chen A. M., Gupta R. S., Brahn E. and Sercarz E. E. (1997): Diversification of T cell responses to carboxy-terminal determinants within the 65-kD heat-shock protein is involved in regulation of autoimmune arthritis. J. Exp. Med., 185, 1307-1316.
123. Moudgil K. D., Grewal I. S., Jensen P. E. and Sercarz E. E. (1996): Unresponsiveness to a self-peptide of mouse lysozyme owing to hindrance of T cell receptor-major histocompatibility complex/peptide interaction caused by flanking epitopic residues. J. Exp. Med., 183, 535-546.
124. Moudgil K. D. and Sercarz E. E. (1993): Dominant determinants in hen eggwhite lysozyme correspond to the cryptic determinants within its self-homologue, mouse lysozyme: implications in shaping of the T cell repertoire and autoimmunity. J. Exp. Med., 178, 2131-2138.
125. Moudgil K. D. and Sercarz E. E. (1994): The T cell repertoire against cryptic self determinants and its involvement in autoimmunity and cancer. Clin. Immunol. Immunopathol., 73, 283-289.
126. Moudgil K. D. and Sercarz E. E. (2000): The self-directed T cell repertoire: its creation and activation. Rev. Immunogenet., 2, 26-37.
127. Moudgil K. D. and Sercarz E. E. (2005): Understanding crypticity is the key to revealing the pathogenesis of autoimmunity. Trends Immunol., 26, 355-359.
128. Moudgil K. D., Sercarz E. E. and Grewal I. S. (1998): Modulation of the immunogenicity of antigenic determinants by their flanking residues. Immunol. Today, 19, 217-220.
129. Moudgil K. D., Southwood S., Ametani A., Kim K., Sette A. and Sercarz E. E. (1999): The self-directed T cell repertoire against mouse lysozyme reflects the influence of the hierarchy of its own determinants and can be engaged by a foreign lysozyme. J. Immunol., 163, 4232-4237.
130. Mukherjee R., Chaturvedi P., Qin H. Y. and Singh B. (2003): CD4+CD25+ regulatory T cells generated in response to insulin B:9-23 peptide prevent adoptive transfer of diabetes by diabetogenic T cells. J. Autoimmun., 21, 221-237.
131. Nakamura K., Kitani A. and Strober W. (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.
132. Nakamura T., Kamogawa Y., Bottomly K. and Flavell R. A. (1997): Polarization of IL-4- and IFN-gamma-producing CD4+ T cells following activation of naive CD4+ T cells. J. Immunol., 158, 1085-1094.
133. Nielsen J., Holm T. L. and Claesson M. H. (2004): CD4+CD25+ regulatory T cells: II. Origin, disease models and clinical aspects. Apmis, 112, 642-650.
134. Nishikawa H., Kato T., Tawara I., Ikeda H., Kuribayashi K., Allen P. M., Schreiber R. D., Old L. J. and Shiku H. (2005): IFN-gamma controls the generation/activation of CD4+ CD25+ regulatory T cells in antitumor immune response. J. Immunol., 175, 4433-4440.
135. Nocentini G., Giunchi L., Ronchetti S., Krausz L. T., Bartoli A., Moraca R., Migliorati G. and Riccardi C. (1997): A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proc. Natl. Acad. Sci. USA, 94, 6216-6221.
136. Ohashi P. S., Oehen S., Buerki K., Pircher H., Ohashi C. T., Odermatt B., Malissen B., Zinkernagel R. M. and Hengartner H. (1991): Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice. Cell, 65, 305-317.
137. Pace L., Pioli C. and Doria G. (2005): IL-4 modulation of CD4+CD25+ T regulatory cell-mediated suppression. J. Immunol., 174, 7645-7653.
138. Palmer E. (2003): Negative selection-β-clearing out the bad apples from the T-cell repertoire. Nat. Rev. Immunol., 3, 383-391.
139. Papiernik M., de Moraes M. L., Pontoux C., Vasseur F. and Penit C. (1998): Regulatory CD4 T cells: expression of IL-2R alpha chain, resistance to clonal deletion and IL-2 dependency. Int. Immunol., 10, 371-378.
140. Pasare C, and Medzhitov R. (2003): Toll pathway-dependent blockade of CD4+CD25+ T cell-mediated suppression by dendritic cells. Science, 299, 1033-1036.
141. Paust S., Lu L., McCarty N. and Cantor H. (2004): Engagement of B7 on effector T cells by regulatory T cells prevents autoimmune disease. Proc. Natl. Acad. Sci. USA, 101, 10398-10403.
142. Peng G., Guo Z., Kiniwa Y., Voo K. S., Peng W., et al. (2005): Toll-like receptor 8-mediated reversal of CD4+ regulatory T cell function. Science, 309, 1380-1384.
143. Perez V. L., Van Parijs L., Biuckians A., Zheng X. X., Strom T. B. and Abbas A. K. (1997): Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement. Immunity, 6, 411-417.
144. Prakken B. J., Samodal R., Le T. D., Giannoni F., Yung G. P., Scavulli J., Amox D., Roord S., de Kleer I., Bonnin D., Lanza P., Berry C., Massa M., Billetta R. and Albani S. (2004): Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. Proc. Natl. Acad. Sci. USA, 101, 4228-4233.
145. Pribyl T. M., Campagnoni C., Kampf K., Handley V. W. and Campagnoni A. T. (1996): The major myelin protein genes are expressed in the human thymus. J. Neurosci. Res., 45, 812-819.
146. Read S., Malmstrom V. and Powrie F. (2000): Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J. Exp. Med., 192, 295-302.
147. Reddy J., Illes Z., Zhang X., Encinas J., Pyrdol J., Nicholson L., Sobel R. A., Wucherpfennig K. W. and Kuchroo V. K. (2004): Myelin proteolipid protein-specific CD4+CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA, 101, 15434-15439.
148. Reddy J., Waldner H., Zhang X., Illes Z., Wucherpfennig K. W., Sobel R. A. and Kuchroo V. K. (2005): Cutting edge: CD4+CD25+ regulatory T cells contribute to gender differences in susceptibility to experimental autoimmune encephalomyelitis. J. Immunol., 175, 5591-5595.
149. Roncarolo M. G., Bacchetta R., Bordignon C., Narula S. and Levings M. K. (2001): Type 1 T regulatory cells. Immunol. Rev., 182, 68-79.
150. Sakaguchi S. (2001): Policing the regulators. Nat. Immunol., 2, 283-284.
151. Sakaguchi S. (2004): Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu. Rev. Immunol., 22, 531-562.
152. Sakaguchi S. and Sakaguchi N. (2005): Regulatory T cells in immunologic self-tolerance and autoimmune disease. Int. Rev. Immunol., 24, 211-226.
153. Sakaguchi S., Sakaguchi N., Asano M., Itoh M. and Toda M. (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.
154. Salomon B., Lenschow D. J., Rhee L., Ashourian N., Singh B., Sharpe A. and Bluestone J. A. (2000): B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity, 12, 431-440.
155. Samy E. T., Parker L. A., Sharp C. P. and Tung K. S. (2005): Continuous control of autoimmune disease by antigen-dependent polyclonal CD4+CD25+ regulatory T cells in the regional lymph node. J. Exp. Med., 202, 771-781.
156. Santos L. M., al-Sabbagh A., Londono A. and Weiner H. L. (1994): Oral tolerance to myelin basic protein induces regulatory TGF-beta-secreting T cells in Peyer's patches of SJL mice. Cell. Immunol., 157, 439-447.
157. Sarween N., Chodos A., Raykundalia C., Khan M., Abbas A. K. and Walker L. S. (2004): CD4+CD25+ cells controlling a pathogenic CD4 response inhibit cytokine differentiation, CXCR-3 expression, and tissue invasion. J. Immunol., 173, 2942-2951.
158. Schubert L. A., Jeffery E., Zhang Y., Ramsdell F. and Ziegler S. F. (2001): Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J. Biol. Chem., 276, 37672-37679.
159. Sercarz E. E., Lehmann P. V., Ametani A., Benichou G., Miller A. and Moudgil K. (1993): Dominance and crypticity of T cell antigenic determinants. Annu. Rev. Immunol., 11, 729-766.
160. Sharif S., Arreaza G. A., Zucker P., Mi Q. S. and Delovitch T. L. (2002): Regulation of autoimmune disease by natural killer T cells. J. Mol. Med., 80, 290-300.
161. Shevach E. M. (2000): Regulatory T cells in autoimmmunity. Annu. Rev. Immunol., 18, 423-449.
162. Shevach E. M. (2002): CD4+ CD25+ suppressor T cells: more questions than answers. Nat. Rev. Immunol., 2, 389-400.
163. Shih F. F., Mandik-Nayak L., Wipke B. T. and Allen P. M. (2004): Massive thymic deletion results in systemic autoimmunity through elimination of CD4+ CD25+ T regulatory cells. J. Exp. Med., 199, 323-335.
164. Shimizu J., Yamazaki S. and Sakaguchi S. (1999): Induction of tumor immunity by removing CD25+ CD4+ T cells: a common basis between tumor immunity and autoimmunity. J. Immunol., 163, 5211-5218.
165. Shimizu J., Yamazaki S., Takahashi T., Ishida Y. and Sakaguchi S. (2002): Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol., 3, 135-142.
166. Singh B., Read S., Asseman C., Malmstrom V., Mottet C., Stephens L. A., Stepankova R., Tlaskalova H. and Powrie F. (2001): Control of intestinal inflammation by regulatory T cells. Immunol. Rev., 182, 190-200.
167. Sinha P., Chi H. H., Kim H. R., Clausen B. E., Pederson B., Sercarz E. E., Forster I. and Moudgil K. D. (2004): Mouse lysozyme-M knockout mice reveal how the self-determinant hierarchy shapes the T cell repertoire against this circulating self antigen in wild-type mice. J. Immunol., 173, 1763-1771.
168. Smith K. M., Olson D. C., Hirose R. and Hanahan D. (1997): Pancreatic gene expression in rare cells of thymic medulla: evidence for functional contribution to T cell tolerance. Int. Immunol., 9, 1355-1365.
169. Song L., Wang J., Wang R., Yu M., Sun Y., Han G., Li Y., Qian J., Scott D. W., Kang Y., Soukhareva N. and Shen B. (2004): Retroviral delivery of GAD-IgG fusion construct induces tolerance and modulates diabetes: a role for CD4+ regulatory T cells and TGF-beta? Gene Ther., 11, 1487-1496.
170. Sospedra M., Ferrer-Francesch X., Dominguez O., Juan M., Foz-Sala M. and Pujol-Borrell R. (1998): Transcription of a broad range of self-antigens in human thymus suggests a role for central mechanisms in tolerance toward peripheral antigens. J. Immunol., 161, 5918-5929.
171. Starr T. K., Jameson S. C. and Hogquist K. A. (2003): Positive and negative selection of T cells. Annu. Rev. Immunol., 21, 139-176.
172. Stasiolek M., Bayas A., Kruse N., Wieczarkowiecz A., Toyka K. V., Gold R. and Selmaj K. (2006): Impaired maturation and altered regulatory function of plasmacytoid dendritic cells in multiple sclerosis. Brain, 129, 1293-1305.
173. Steinman R. M. and Nussenzweig M. C. (2002): Avoiding horror autotoxicus: the importance of dendritic cells in peripheral T cell tolerance. Proc. Natl. Acad. Sci. USA, 99, 351-358.
174. Stephens G. L., McHugh R. S., Whitters M. J., Young D. A, Luxenberg D., Carreno B. M., Collins M. and Shevach E. M. (2004): Engagement of glucocorticoid-induced TNFR family-related receptor on effector T cells by its ligand mediates resistance to suppression by CD4+CD25+ T cells. J. Immunol., 173, 5008-5020.
175. Sullivan B. A. and Kronenberg M. (2005): Activation or anergy: NKT cells are stunned by alpha-galactosylceramide. J. Clin. Invest., 115, 2328-2329.
176. Sundstedt A., O'Neill E. J., Nicolson K. S. and Wraith D. C. (2003): Role for IL-10 in suppression mediated by peptide-induced regulatory T cells in vivo. J. Immunol., 170, 1240-1248.
177. Suri-Payer E., Amar A. Z., Thornton A. M. and Shevach E. M. (1998): 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., 160, 1212-1218.
178. Taams L. S., Vukmanovic-Stejic M., Smith J., Dunne P. J., Fletcher J. M., Plunkett F. J., Ebeling S. B., Lombardi G., Rustin M. H., Bijlsma J. W., Lafeber F. P., Salmon M. and Akbar A. N. (2002): Antigen-specific T cell suppression by human CD4+CD25+ regulatory T cells. Eur. J. Immunol., 32, 1621-1630.
179. Takahama Y. (2006): Journey through the thymus: stromal guides for T-cell development and selection. Nat. Rev. Immunol., 6, 127-135.
180. Takahashi T., Kuniyasu Y., Toda M., Sakaguchi N., Itoh M., Iwata M., Shimizu J. and Sakaguchi S. (1998): 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., 10, 1969-1980.
181. Takahashi T., Tagami T., Yamazaki S., Uede T., Shimizu J., Sakaguchi N., Mak T. W. and Sakaguchi S. (2000): Immunologic self-tolerance maintained by CD25(+)CD4(+) regulatory T cells constitutively expressing cytotoxic T lymphocyte-associated antigen 4. J. Exp. Med., 192, 303-310.
182. Tanchot C., Vasseur F., Pontoux C., Garcia C. and Sarukhan A. (2004): Immune regulation by self-reactive T cells is antigen specific. J. Immunol., 172, 4285-4291.
183. Tang Q., Henriksen K. J., Bi M., Finger E. B., Szot G., Ye J., Masteller E. L., McDevitt H., Bonyhadi M. and Bluestone J. A. (2004): In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J. Exp. Med., 199, 1455-1465.
184. Tarbell K. V., Yamazaki S., Olson K., Toy P. and Steinman R. M. (2004): CD25+ CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J. Exp. Med., 199, 1467-1477.
185. Targoni O. S. and Lehmann P. V. (1998): Endogenous myelin basic protein inactivates the high avidity T cell repertoire. J. Exp. Med., 187, 2055-2063.
186. Taylor P. A., Lees C. J., Fournier S., Allison J. P., Sharpe A. H. and Blazar B. R. (2004): B7 expression on T cells down-regulates immune responses through CTLA-4 ligation via T-T interactions [corrections]. J. Immunol., 172, 34-39.
187. Thornton A. M., Donovan E. E., Piccirillo C. A. and Shevach E. M. (2004): Cutting edge: IL-2 is critically required for the in vitro activation of CD4+CD25+ T cell suppressor function. J. Immunol., 172, 6519-6523.
188. Thorstenson K. M. and Khoruts A. (2001): Generation of anergic and potentially immunoregulatory CD25+ CD4 T cells in vivo after induction of peripheral tolerance with intravenous or oral antigen. J. Immunol., 167, 188-195.
189. Uchida D., Hatakeyama S., Matsushima A., Han H., Ishido S., Hotta H., Kudoh J., Shimizu N., Doucas V., Nakayama K. I., Kuroda N. and Matsumoto M. (2004): AIRE functions as an E3 ubiquitin ligase. J. Exp. Med., 199, 167-172.
190. van Santen H. M., Benoist C. and Mathis D. (2004): 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.
191. Veldman C., Nagel A. and Hertl M. (2006): Type I regulatory T cells in autoimmunity and inflammatory diseases. Int. Arch. Allergy Immunol., 140, 174-183.
192. Venanzi E. S., Benoist C. and Mathis D. (2004): Good riddance: thymocyte clonal deletion prevents autoimmunity. Curr. Opin. Immunol., 16, 197-202.
193. Viglietta V., Baecher-Allan C., Weiner H. L. and Hafler D. A. (2004): Loss of functional suppression by CD4+ +CD25+ regulatory T cells in patients with multiple sclerosis. J. Exp. Med., 199, 971-979.
194. Volkmann A., Zal T. and Stockinger B. (1997): Antigen-presenting cells in the thymus that can negatively select MHC class II-restricted T cells recognizing a circulating self antigen. J. Immunol., 158, 693-706.
195. von Boehmer H. (2005): Mechanisms of suppression by suppressor T cells. Nat. Immunol., 6, 338-344.
196. von Boehmer H., Aifantis I., Gounari F., Azogui O., Haughn L., Apostolou I., Jaeckel E., Grassi F. and Klein L. (2003): Thymic selection revisited: how essential is it? Immunol. Rev., 191, 62-78.
197. Walker L. S., Chodos A., Eggena M., Dooms H. and Abbas A. K. (2003): Antigen-dependent proliferation of CD4+ CD25+ regulatory T cells in vivo. J. Exp. Med., 198, 249-258.
198. Walker M. R., Kasprowicz D. J., Gersuk V. H., Benard A., Van Landeghen M., Buckner J. H. and Ziegler S. F. (2003): Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25- T cells. J. Clin. Invest., 112, 1437-1443.
199. Wang H. Y., Lee D. A., Peng G., Guo Z., Li Y., Kiniwa Y., Shevach E. M. and Wang R. F. (2004): Tumor-specific human CD4+ regulatory T cells and their ligands: implications for immunotherapy. Immunity, 20, 107-118.
200. Wang H. Y., Peng G., Guo Z., Shevach E. M. and Wang R. F. (2005): Recognition of a new ARTC1 peptide ligand uniquely expressed in tumor cells by antigen-specific CD4+ regulatory T cells. J. Immunol., 174, 2661-2670.
201. Wang Z. Y., Link H., Ljungdahl A., Hojeberg B., Link J., He B., Qiao J., Melms A. and Olsson T. (1994): Induction of interferon-gamma, interleukin-4, and transforming growth factor-beta in rats orally tolerized against experimental autoimmune myasthenia gravis. Cell. Immunol., 157, 353-368.
202. Weiner H. L., Friedman A., Miller A., Khoury S. J., al-Sabbagh A., Santos L., Sayegh M., Nussenblatt R. B., Trentham D. E. and Hafler D. A. (1994): Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu. Rev. Immunol., 12, 809-837.
203. Wekerle H., Schwab M., Linington C. and Meyermann R. (1986): Antigen presentation in the peripheral nervous system: Schwann cells present endogenous myelin autoantigens to lymphocytes. Eur. J. Immunol., 16, 1551-1557.
204. Wilson M. T. and Van Kaer L. (2003): Natural killer T cells as targets for therapeutic intervention in autoimmune diseases. Curr. Pharm. Des., 9, 201-220.
205. Wing K., Suri-Payer E. and Rudin A. (2005): CD4+CD25+-regulatory T cells from mouse to man. Scand. J. Immunol., 62, 1-15.
206. Wohlfert E. A., Callahan M. K. and Clark R. B. 2004. Resistance to CD4+CD25+ regulatory T cells and TGF-beta in Cbl-b-/- mice. J. Immunol., 173, 1059-1065.
207. Young D. A., Lowe L. D., Booth S. S., Whitters M. J., Nicholson L., Kuchroo V. K. and Collins M. (2000): IL-4, IL-10, IL-13, and TGF-beta from an altered peptide ligand-specific Th2 cell clone down-regulate adoptive transfer of experimental autoimmune encephalomyelitis. J. Immunol., 164, 3563-3572.
208. Yu P., Gregg R. K., Bell J. J., Ellis J. S., Divekar R., Lee H. H., Jain R., Waldner H., Hardaway J. C., Collins M., Kuchroo V. K. and Zaghouani H. (2005): Specific T regulatory cells display broad suppressive functions against experimental allergic encephalomyelitis upon activation with cognate antigen. J. Immunol., 174, 6772-6780.
209. Zal T., Volkmann A. and Stockinger B. (1994): Mechanisms of tolerance induction in major histocompatibility complex class II-restricted T cells specific for a blood-borne self-antigen. J. Exp. Med., 180, 2089-2099.
210. Zhang M., Fukushima A., Vistica B. P., Kim S. J., Hung L., Wawrousek E. F., Egwuagu C. E., Lee R. S., Whitcup S. M. and Gery I. (2001): Skewed abrogation of tolerance to a neo self-antigen in double-transgenic mice coexpressing the antigen with interleukin-1beta or interferon-gamma. Cell. Immunol., 207, 6-12.
211. Zhang X., Reddy J., Ochi H., Frenkel D., Kuchroo V. K. and Weiner H. L. (2006): Recovery from experimental allergic encephalomyelitis is TGF-beta dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells. Int. Immunol., 18, 495-503.
212. Zheng S. G., Gray J. D., Ohtsuka K., Yamagiwa S. and Horwitz D. A. (2002): Generation ex vivo of TGF-beta-producing regulatory T cells from CD4+CD25- precursors. J. Immunol., 169, 4183-4189.
213. Zhou D., Mattner J., Cantu C. 3rd., Schrantz N., Yin N., Gao Y., Sagiv Y., Hudspeth K., Wu Y. P., Yamashita T., Teneberg S., Wang D., Proia R. L., Levery S. B., Savage P. B., Teyton L. and Bendelac A. (2004): Lysosomal glycosphingolipid recognition by NKT cells. Science, 306, 1786-1789.
214. Zinkernagel R. M. and Doherty P. C. (1974): Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature, 248, 701-702.