The gut mucosa as a site for induction of regulatory T-cells

Current Pharmaceutical Design

Volumn 15, Issue 11, 2009, Pages 1191-1202

  Mizrahi, Meir ^a   Ilan, Yaron ^a  

^a HADASSAH HEBREW UNIVERSITY MEDICAL CENTER   (Israel)

Author keywords

Oral tolerance; Regulatory T cells

Indexed keywords

AUTOANTIBODY; AUTOANTIGEN; CD8 ANTIGEN; CYTOKINE; IMMUNOGLOBULIN A; LATENCY ASSOCIATED PEPTIDE; MONOCLONAL ANTIBODY CD3; PROTEIN DERIVATIVE; TRANSFORMING GROWTH FACTOR BETA ANTIBODY;

ACUTE GRAFT REJECTION; ADAPTIVE IMMUNITY; ALLERGIC ENCEPHALOMYELITIS; ANEMIA; ANTIGEN ANTIBODY REACTION; ANTIGEN PRESENTING CELL; ANTIGEN SPECIFICITY; ANTIGENICITY; APOPTOSIS; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE; BACTERIAL FLORA; BYSTANDER EFFECT; CD25+ T LYMPHOCYTE; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CELL SURVIVAL; CELL THERAPY; CELLULAR IMMUNITY; COLITIS; CROHN DISEASE; CROSS REACTION; CYTOKINE PRODUCTION; DENDRITIC CELL; DISEASE COURSE; DRUG ERUPTION; DRUG FEVER; DRUG RESEARCH; DRUG TARGETING; ENTERITIS; ENTEROPATHY; EOSINOPHIL; FOOD INTAKE; HELPER CELL; HUMAN; HUMORAL IMMUNITY; IMMUNOGLOBULIN PRODUCTION; IMMUNOLOGICAL TOLERANCE; IMMUNOMODULATION; IMMUNOPATHOGENESIS; IMMUNOPATHOLOGY; IMMUNOREGULATION; IMMUNOSTIMULATION; INFLAMMATORY CELL; INNATE IMMUNITY; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE MUCOSA; INTESTINE VILLUS; LYMPHATIC DRAINAGE; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE FUNCTION; LYMPHOCYTE HOMING; MAST CELL; MESENTERY LYMPH NODE; NONHUMAN; PEYER PATCH; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; T LYMPHOCYTE ACTIVATION; TARGET CELL; TH2 CELL; TH3 CELL;

ANIMALS; HUMANS; IMMUNE SYSTEM; IMMUNE TOLERANCE; INTESTINAL MUCOSA; T-LYMPHOCYTES, REGULATORY;

EID: 65649089803     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161209787846784     Document Type: Review

References (200)

1. Dahan S, Roth-Walter F, Arnaboldi P, Agarwal S, Mayer L. Epithelia: lymphocyte interactions in the gut. Immunol Rev 2007; 215: 243-53.
2. Sherman MA, Kalman D. Initiation and resolution of mucosal inflammation. Immunol Res 2004; 29: 241-52.
3. Macdonald TT, Monteleone G. Immunity, inflammation, and allergy in the gut. Science 2005; 307: 1920-5.,
4. Spahn TW, Kucharzik T. Modulating the intestinal immune system: the role of lymphotoxin and GALT organs. Gut 2004; 53: 456-65.
5. Mowat AM. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol 2003; 3: 331-41.
6. Campbell N, Yio XY, So LP, Li Y, Mayer L. The intestinal epithelial cell: processing and presentation of antigen to the mucosal immune system. Immunol Rev 1999; 172: 315-24.
7. Kelsall B. Innate and adaptive mechanisms to control of pathological intestinal inflammation. J Pathol 2008; 214: 242-59.
8. Sansonetti PJ. War and peace at mucosal surfaces. Nat Rev Immunol 2004; 4: 953-64.
9. Miller H, Zhang J, Kuolee R, Patel GB, Chen W. Intestinal M cells: the fallible sentinels? World J Gastroenterol 2007; 13: 1477-86.
10. Johansson-Lindbom B, Agace WW. Generation of gut-homing T cells and their localization to the small intestinal mucosa. Immunol Rev 2007; 215: 226-42.
11. Thompson-Chagoyan OC, Maldonado J, Gil A. Colonization and impact of disease and other factors on intestinal microbiota. Dig Dis Sci 2007; 52: 2069-77.
12. Marchesi J, Shanahan F. The normal intestinal microbiota. Curr Opin Infect Dis 2007; 20: 508-13.
13. Chin R, Wang J, Fu YX. Lymphoid microenvironment in the gut for immunoglobulin A and inflammation. Immunol Rev 2003; 195: 190-201.
14. Makala LH, Suzuki N, Nagasawa H. Peyer's patches: organized lymphoid structures for the induction of mucosal immune responses in the intestine. Pathobiology 2002; 70: 55-68.
15. Okamoto K, Fukatsu K, Ueno C, Shinto E, Hashiguchi Y, Nagayoshi H, et al. T lymphocyte numbers in human gut associated lymphoid tissue are reduced without enteral nutrition. JPEN J Parenter Enteral Nutr 2005; 29: 56-8.
16. Corthesy B. Roundtrip ticket for secretory IgA: role in mucosal homeostasis? J Immunol 2007; 178: 27-32.
17. Berin MC, Li H, Sperber K. Antibody-mediated antigen sampling across intestinal epithelial barriers. Ann N Y Acad Sci 2006; 1072: 253-61.
18. Suzuki K, Ha SA, Tsuji M, Fagarasan S. Intestinal IgA synthesis: a primitive form of adaptive immunity that regulates microbial communities in the gut. Semin Immunol 2007; 19: 127-35.
19. Brandtzaeg P, Kiyono H, Pabst B, Russell MW. Terminology: nomenclature of mucosa-associated lymphoid tissue. Mucosal Immunol 2008; 1: 31-7.
20. Fagarasan S. Intestinal IgA synthesis: a primitive form of adaptive immunity that regulates microbial communities in the gut. Curr Top Microbiol Immunol 2006; 308: 137-53.
21. Macpherson AJ. IgA adaptation to the presence of commensal bacteria in the intestine. Curr Top Microbiol Immunol 2006; 308: 117-36.
22. Liebler-Tenorio EM, Pabst R. MALT structure and function in farm animals. Vet Res 2006; 37: 257-80.
23. Pabst R, Rothkotter HJ. Structure and function of the gut mucosal immune system. Adv Exp Med Biol 2006; 579: 1-14.
24. Brandtzaeg P, Johansen FE, Baekkevold ES, Carlsen HS, Farstad IN. The traffic of mucosal lymphocytes to extraintestinal sites. J Pediatr Gastroenterol Nutr 2004; 39(Suppl 3): S725-6.
25. Kunisawa J, Fukuyama S, Kiyono H. Mucosa-associated lymphoid tissues in the aerodigestive tract: their shared and divergent traits and their importance to the orchestration of the mucosal immune system. Curr Mol Med 2005; 5: 557-72.
26. Man AL, Prieto-Garcia ME, Nicoletti C. Improving M cell mediated transport across mucosal barriers: do certain bacteria hold the keys? Immunology 2004; 113: 15-22.
27. Brandtzaeg P, Johansen FE. Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunol Rev 2005; 206: 32-63.
28. Kwa SF, Beverley P, Smith AL. Peyer's patches are required for the induction of rapid Th1 responses in the gut and mesenteric lymph nodes during an enteric infection. J Immunol 2006; 176: 7533-41.
29. Velazquez P, Wei B, Braun J. Surveillance B lymphocytes and mucosal immunoregulation. Springer Semin Immunopathol 2005; 26: 453-62.
30. Brandtzaeg P, Farstad IN, Johansen FE, Morton HC, Norderhaug IN, Yamanaka T. The B-cell system of human mucosae and exocrine glands. Immunol Rev 1999; 171: 45-87.
31. Ganusov VV, De Boer RJ. Do most lymphocytes in humans really reside in the gut? Trends Immunol 2007; 28: 514-8.
32. Casola S, Rajewsky K. B cell recruitment and selection in mouse GALT germinal centers. Curr Top Microbiol Immunol 2006; 308: 155-71.
33. Iweala OI, Nagler CR. Immune privilege in the gut: the establishment and maintenance of non-responsiveness to dietary antigens and commensal flora. Immunol Rev 2006; 213: 82-100.
34. Kraal G, Samsom JN, Mebius RE. The importance of regional lymph nodes for mucosal tolerance. Immunol Rev 2006; 213: 119-30.
35. Kunisawa J, Takahashi I, Kiyono H. Intraepithelial lymphocytes: their shared and divergent immunological behaviors in the small and large intestine. Immunol Rev 2007; 215: 136-53.
36. McGhee JR, Kunisawa J, Kiyono H. Gut lymphocyte migration: we are halfway 'home'. Trends Immunol 2007; 28: 150-3.
37. Brandtzaeg P, Pabst R. Let's go mucosal: communication on slippery ground. Trends Immunol 2004; 25: 570-7.
38. Brandtzaeg PE. Current understanding of gastrointestinal immunoregulation and its relation to food allergy. Ann N Y Acad Sci 2002; 964: 13-45.
39. Brandtzaeg P, Baekkevold ES, Morton HC. From B to A the mucosal way. Nat Immunol 2001; 2: 1093-4.
40. Boursier L, Gordon JN, Thiagamoorthy S, Edgeworth JD, Spencer J. Human intestinal IgA response is generated in the organized gut-associated lymphoid tissue but not in the lamina propria. Gastroenterology 2005; 128: 1879-89.
41. He B, Xu W, Santini PA, Polydorides AD, Chiu A, Estrella J, et al. Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. Immunity 2007; 26: 812-26.
42. van Driel IR, Ang DK. Role of regulatory T cells in gastrointestinal inflammatory disease. J Gastroenterol Hepatol 2008; 23: 171-7.
43. Lefrancois L, Puddington L. Intestinal and pulmonary mucosal T cells: local heroes fight to maintain the status quo. Annu Rev Immunol 2006; 24: 681-704.
44. Rav-Acha M, Sassa D, Ilan Y, Milgalter E, Lotan C. [Surgical intervention in infective endocarditis: indications and timing]. Harefuah 2005; 144: 421-5, 453.
45. Moghaddami M, Cummins A, Mayrhofer G. Lymphocyte-filled villi: comparison with other lymphoid aggregations in the mucosa of the human small intestine. Gastroenterology 1998; 115: 1414-25.
46. Onai N, Kitabatake M, Zhang YY, Ishikawa H, Ishikawa S, Matsushima K. Pivotal role of CCL25 (TECK)-CCR9 in the formation of gut cryptopatches and consequent appearance of intestinal intraepithelial T lymphocytes. Int Immunol 2002; 14: 687-94.
47. Guy-Grand D, Azogui O, Celli S, Darche S, Nussenzweig MC, Kourilsky P, et al. Extrathymic T cell lymphopoiesis: ontogeny and contribution to gut intraepithelial lymphocytes in athymic and euthymic mice. J Exp Med 2003; 197: 333-41.
48. Craig SW, Cebra JJ. Peyer's patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit. J Exp Med 1971; 134: 188-200.
49. McWilliams M, Phillips-Quagliata JM, Lamm ME. Mesenteric lymph node B lymphoblasts which home to the small intestine are precommitted to IgA synthesis. J Exp Med 1977; 145: 866-75.
50. MacDonald TT, Spencer J. Ontogeny of the mucosal immune response. Springer Semin Immunopathol 1990; 12: 129-37.
51. Trepel F. Number and distribution of lymphocytes in man. A critical analysis. Klin Wochenschr 1974; 52: 511-5.
52. O'Leary AD, Sweeney EC. Lymphoglandular complexes of the colon: structure and distribution. Histopathology 1986; 10: 267-83.
53. Dohi T, Rennert PD, Fujihashi K, Kiyono H, Shirai Y, Kawamura YI, et al. Elimination of colonic patches with lymphotoxin beta receptor-Ig prevents Th2 cell-type colitis. J Immunol 2001; 167: 2781-90.
54. Saurer L, McCullough KC, Summerfield A. In vitro induction of mucosa-type dendritic cells by all-trans retinoic acid. J Immunol 2007; 179: 3504-14.
55. Wendland M, Czeloth N, Mach N, Malissen B, Kremmer E, Pabst O, et al. CCR9 is a homing receptor for plasmacytoid dendritic cells to the small intestine. Proc Natl Acad Sci USA 2007; 104: 6347-52.
56. van der Heijden PJ, Stok W, Bianchi AT. Contribution of immunoglobulin-secreting cells in the murine small intestine to the total 'background' immunoglobulin production. Immunology 1987; 62: 551-5.
57. Faria AM, Weiner HL. Oral tolerance. Immunol Rev 2005; 206: 232-59.
58. Smith DW, Nagler-Anderson C. Preventing intolerance: the induction of nonresponsiveness to dietary and microbial antigens in the intestinal mucosa. J Immunol 2005; 174: 3851-7.
59. Brandtzaeg P. Development and basic mechanisms of human gut immunity. Nutr Rev 1998; 56: S5-18.
60. El Haj M, Ya'acov AB, Lalazar G, Ilan Y. Potential role of NKT regulatory cell ligands for the treatment of immune mediated colitis. World J Gastroenterol 2007; 13: 5799-804.
61. Pabst O, Herbrand H, Friedrichsen M, Velaga S, Dorsch M, Berhardt G, et al. Adaptation of solitary intestinal lymphoid tissue in response to microbiota and chemokine receptor CCR7 signaling. J Immunol 2006; 177: 6824-32.
62. Faria AM, Weiner HL. Oral tolerance: therapeutic implications for autoimmune diseases. Clin Dev Immunol 2006; 13: 143-57.
63. Brandtzaeg P, Prydz H. Direct evidence for an integrated function of J chain and secretory component in epithelial transport of immunoglobulins. Nature 1984; 311: 71-3.
64. Shlomai A, Trop S, Gotsman I, Jurim O, Diment J, Alper R, et al. Immunomodulation of experimental colitis: the role of NK1.1 liver lymphocytes and surrogate antigens--bystander effect. J Pathol 2001; 195: 498-507.
65. Parrott DM. The gut as a lymphoid organ. Clin Gastroenterol 1976; 5: 211-28.
66. Roux ME, McWilliams M, Phillips-Quagliata JM, Lamm ME. Differentiation pathway of Peyer's patch precursors of IgA plasma cells in the secretory immune system. Cell Immunol 1981; 61: 141-53.
67. Weiner HL, Gonnella PA, Slavin A, Maron R. Oral tolerance: cytokine milieu in the gut and modulation of tolerance by cytokines. Res Immunol 1997; 148: 528-33.
68. Weiner HL, Komagata Y. Oral tolerance and the treatment of rheumatoid arthritis. Springer Semin Immunopathol 1998; 20: 289-308.
69. Russo M, Jancar S, Pereira de Siqueira AL, Mengel J, Gomes E, Ficker SM, et al. Prevention of lung eosinophilic inflammation by oral tolerance. Immunol Lett 1998; 61: 15-23.
70. Cottrez F, Manca F, Dalgleish AG, Arenzana-Seisdedos F, Capron A, Groux H. Priming of human CD4+ antigen-specific T cells to undergo apoptosis by HIV-infected monocytes. A two-step mechanism involving the gp120 molecule. J Clin Invest 1997; 99: 257-66.
71. Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997; 389: 737-42.
72. Groux H, Sornasse T, Cottrez F, de Vries JE, Coffman RL, Roncarolo MG, et al. Induction of human T helper cell type 1 differentiation results in loss of IFN-gamma receptor beta-chain expression. J Immunol 1997; 158: 5627-31.
73. Garside P, Mowat AM. Polarization of Th-cell responses: a phylogenetic consequence of nonspecific immune defence? Immunol Today 1995; 16: 220-3.
74. Garside P, Steel M, Liew FY, Mowat AM. CD4+ but not CD8+ T cells are required for the induction of oral tolerance. Int Immunol 1995; 7: 501-4.
75. Garside P, Steel M, Worthey EA, Satoskar A, Alexander J, Bluethmann H, et al. T helper 2 cells are subject to high dose oral tolerance and are not essential for its induction. J Immunol 1995; 154: 5649-55.
76. Chen Y, Inobe J, Weiner HL. Induction of oral tolerance to myelin basic protein in CD8-depleted mice: both CD4+ and CD8+ cells mediate active suppression. J Immunol 1995; 155: 910-6.
77. Mowat AM. Basic mechanisms and clinical implications of oral tolerance. Curr Opin Gastroenterol 1999; 15: 546-56.
78. Mowat AM, Steel M, Leishman AJ, Garside P. Normal induction of oral tolerance in the absence of a functional IL-12-dependent IFN-gamma signaling pathway. J Immunol 1999; 163: 4728-36.
79. Kweon MN, Fujihashi K, VanCott JL, Higuchi K, Yamamoto M, McGhee JR, et al. Lack of orally induced systemic unresponsiveness in IFN-gamma knockout mice. J Immunol 1998; 160: 1687-93.
80. Lee H, Barrett TA. Oral tolerance therapy in an experimental model of colitis. Am J Gastroenterol 2000; 95: 861.
81. Gonnella PA, Waldner HP, Weiner HL. B cell-deficient (mu MT) mice have alterations in the cytokine microenvironment of the gutassociated lymphoid tissue (GALT) and a defect in the low dose mechanism of oral tolerance. J Immunol 2001; 166: 4456-64.
82. Faria AM, Weiner HL. Oral tolerance and TGF-beta-producing cells. Inflamm Allergy Drug Targets 2006; 5: 179-90.
83. Read S, Malmstrom V, Powrie F. Cytotoxic T lymphocyteassociated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 2000; 192: 295-302.
84. Salomon B, Lenschow DJ, Rhee L, Ashourian N, Singh B, Sharpe A, et al. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 2000; 12: 431-40.
85. 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.
86. 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.
87. Baecher-Allan C, Hafler DA. Suppressor T cells in human diseases. J Exp Med 2004; 200: 273-6.
88. Basten A, Fazekas de St Groth B. Special regulatory T-cell review: T-cell dependent suppression revisited. Immunology 2008; 123: 33-9.
89. Levy L, Ilan Y. Oral immune regulation: a new mode of therapy against chronic viral infections. Recent Patents Anti-Infect Drug Disc 2007; 2: 217-21.
90. Sakaguchi S, Wing K, Miyara M. Regulatory T cells - a brief history and perspective. Eur J Immunol 2007; 37(Suppl 1): S116-23.
91. Belkaid Y. Regulatory T cells and infection: a dangerous necessity. Nat Rev Immunol 2007; 7: 875-88.
92. Belkaid Y, Rouse BT. Natural regulatory T cells in infectious disease. Nat Immunol 2005; 6: 353-60.
93. Maron R, Blogg NS, Polanski M, Hancock W, Weiner HL. Oral tolerance to insulin and the insulin B-chain: cell lines and cytokine patterns. Ann N Y Acad Sci 1996; 778: 346-57.
94. Maron R, Guerau-de-Arellano M, Zhang X, Weiner HL. Oral administration of insulin to neonates suppresses spontaneous and cyclophosphamide induced diabetes in the NOD mouse. J Autoimmun 2001; 16: 21-8.
95. Sayegh MH, Khoury SJ, Hancock WW, Weiner HL, Carpenter CB. Induction of immunity and oral tolerance with polymorphic class II major histocompatibility complex allopeptides in the rat. Proc Natl Acad Sci USA 1992; 89: 7762-6.
96. Sayegh MH, Khoury SJ, Hancock WW, Weiner HL, Carpenter CB. Induction of immunity and oral tolerance to alloantigen by polymorphic class II major histocompatibility complex allopeptides in the rat. Transplant Proc 1993; 25: 357-8.
97. Sayegh MH, Khoury SJ, Hancock WW, Weiner HL, Carpenter CB. Mechanisms of oral tolerance by MHC peptides. Ann N Y Acad Sci 1996; 778: 338-45.
98. Slavin AJ, Maron R, Weiner HL. Mucosal administration of IL-10 enhances oral tolerance in autoimmune encephalomyelitis and diabetes. Int Immunol 2001; 13: 825-33.
99. Inobe J, Slavin AJ, Komagata Y, Chen Y, Liu L, Weiner HL. IL-4 is a differentiation factor for transforming growth factor-beta secreting Th3 cells and oral administration of IL-4 enhances oral tolerance in experimental allergic encephalomyelitis. Eur J Immunol 1998; 28: 2780-90.
100. Allez M, Mayer L. Regulatory T cells: peace keepers in the gut. Inflamm Bowel Dis 2004; 10: 666-76.
101. Chen W, Perruche S, Li J. CD4+CD25+ T regulatory cells and TGF-beta in mucosal immune system: the good and the bad. Curr Med Chem 2007; 14: 2245-9.
102. Izcue A, Powrie F. Special regulatory T-cell review: Regulatory T cells and the intestinal tract - patrolling the frontier. Immunology 2008; 123: 6-10.
103. Ding Y, Shen S, Lino AC, Curotto de Lafaille MA, Lafaille JJ. Beta-catenin stabilization extends regulatory T cell survival and induces anergy in nonregulatory T cells. Nat Med 2008; 14: 162-9.
104. Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007; 450: 566-9.
105. Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4+ CD25+Foxp3+ regulatory T cells induce cytokine deprivationmediated apoptosis of effector CD4+ T cells. Nat Immunol 2007; 8: 1353-62.
106. Chen Y, Kuchroo VK, Inobe J, Hafler DA, Weiner HL. Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 1994; 265: 1237-40.
107. Zhang X, Izikson L, Liu L, Weiner HL. Activation of CD25(+) CD4(+) regulatory T cells by oral antigen administration. J Immunol 2001; 167: 4245-53.
108. Chen W, Jin W, Tian H, Sicurello P, Frank M, Orenstein JM, et al. Requirement for transforming growth factor beta1 in controlling T cell apoptosis. J Exp Med 2001; 194: 439-53.
109. Ochi H, Abraham M, Ishikawa H, Frenkel D, Yang K, Basso AS, et al. Oral CD3-specific antibody suppresses autoimmune encephalomyelitis by inducing CD4+ CD25- LAP+ T cells. Nat Med 2006; 12: 627-35.
110. Oida T, Xu L, Weiner HL, Kitani A, Strober W. TGF-betamediated suppression by CD4+CD25+ T cells is facilitated by CTLA-4 signaling. J Immunol 2006; 177: 2331-9.
111. Oida T, Zhang X, Goto M, Hachimura S, Totsuka M, Kaminogawa S, et al. CD4+CD25- T cells that express latency-associated peptide on the surface suppress CD4+CD45RBhigh-induced colitis by a TGF-beta-dependent mechanism. J Immunol 2003; 170: 2516-22.
112. Gandhi R, Anderson DE, Weiner HL. Cutting Edge: Immature human dendritic cells express latency-associated peptide and inhibit T cell activation in a TGF-beta-dependent manner. J Immunol 2007; 178: 4017-21.
113. Nicholson LB, Greer JM, Sobel RA, Lees MB, Kuchroo VK. An altered peptide ligand mediates immune deviation and prevents autoimmune encephalomyelitis. Immunity 1995; 3: 397-405.
114. Chen Y, Inobe J, Kuchroo VK, Baron JL, Janeway CA, Jr., Weiner HL. Oral tolerance in myelin basic protein T-cell receptor transgenic mice: suppression of autoimmune encephalomyelitis and dose-dependent induction of regulatory cells. Proc Natl Acad Sci USA 1996; 93: 388-91.
115. Chen Y, Inobe J, Marks R, Gonnella P, Kuchroo VK, Weiner HL. Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature 1995; 376: 177-80.
116. Miller A, Lider O, Abramsky O, Weiner HL. Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals. Eur J Immunol 1994; 24: 1026-32.
117. Miller A, Lider O, Roberts AB, Sporn MB, Weiner HL. Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of transforming growth factor beta after antigen-specific triggering. Proc Natl Acad Sci USA 1992; 89: 421-5.
118. Miller A, Lider O, Weiner HL. Antigen-driven bystander suppression after oral administration of antigens. J Exp Med 1991; 174: 791-8.
119. Miller A, Zhang ZJ, Sobel RA, al-Sabbagh A, Weiner HL. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein. VI. Suppression of adoptively transferred disease and differential effects of oral vs. intravenous tolerization. J Neuroimmunol 1993; 46: 73-82.
120. Nakamura K, Kitani A, Fuss I, Pedersen A, Harada N, Nawata H, et al. TGF-beta 1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice. J Immunol 2004; 172: 834-42.
121. Nakamura K, Kitani A, Strober W. Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med 2001; 194: 629-44.
122. Kitani A, Fuss I, Nakamura K, Kumaki F, Usui T, Strober W. Transforming growth factor (TGF)-beta1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGFbeta1- mediated fibrosis. J Exp Med 2003; 198: 1179-88.
123. Cernea S, Herold KC. Drug insight: New immunomodulatory therapies in type 1 diabetes. Nat Clin Pract Endocrinol Metab 2006; 2: 89-98.
124. Chatenoud L. CD3-specific antibodies as promising tools to aim at immune tolerance in the clinic. Int Rev Immunol 2006; 25: 215-33.
125. Creput C, Durrbach A, Deroure B, Charpentier B. New therapeutic targets for antibodies and recombinant proteins in organ transplantation. Curr Opin Mol Ther 2007; 9: 153-9.
126. Kuiper J, van Puijvelde GH, van Wanrooij EJ, van Es T, Habets K, Hauer AD, et al. Immunomodulation of the inflammatory response in atherosclerosis. Curr Opin Lipidol 2007; 18: 521-6.
127. Chatenoud L, Bluestone JA. CD3-specific antibodies: a portal to the treatment of autoimmunity. Nat Rev Immunol 2007; 7: 622-32.
128. Chatenoud L, Thervet E, Primo J, Bach JF. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc Natl Acad Sci USA 1994; 91: 123-7.
129. Ishikawa H, Ochi H, Chen ML, Frenkel D, Maron R, Weiner HL. Inhibition of autoimmune diabetes by oral administration of anti-CD3 monoclonal antibody. Diabetes 2007; 56: 2103-9.
130. von Boehmer H. Oral tolerance: is it all retinoic acid? J Exp Med 2007; 204: 1737-9.
131. Abraham M, Karni A, Dembinsky A, Miller A, Gandhi R, Anderson D, et al. In vitro induction of regulatory T cells by anti-CD3 antibody in humans. J Autoimmun 2008; 30: 21-8.
132. Karni A, Koldzic DN, Bharanidharan P, Khoury SJ, Weiner HL. IL-18 is linked to raised IFN-gamma in multiple sclerosis and is induced by activated CD4(+) T cells via CD40-CD40 ligand interactions. J Neuroimmunol 2002; 125: 134-40.
133. Wu HY, Monsonego A, Weiner HL. The mechanism of nasal tolerance in lupus prone mice is T-cell anergy induced by immature B cells that lack B7 expression. J Autoimmun 2006; 26: 116-26.
134. Zhang X, Reddy J, Ochi H, Frenkel D, Kuchroo VK, Weiner HL. Recovery from experimental allergic encephalomyelitis is TGFbeta dependent and associated with increases in CD4+LAP+ and CD4+CD25+ T cells. Int Immunol 2006; 18: 495-503.
135. Allez M, Brimnes J, Dotan I, Mayer L. Expansion of CD8+ T cells with regulatory function after interaction with intestinal epithelial cells. Gastroenterology 2002; 123: 1516-26.
136. Brimnes J, Allez M, Dotan I, Shao L, Nakazawa A, Mayer L. Defects in CD8+ regulatory T cells in the lamina propria of patients with inflammatory bowel disease. J Immunol 2005; 174: 5814-22.
137. den Haan JM, Bevan MJ. Antigen presentation to CD8+ T cells: cross-priming in infectious diseases. Curr Opin Immunol 2001; 13: 437-41.
138. Miller JF, Kurts C, Allison J, Kosaka H, Carbone F, Heath WR. Induction of peripheral CD8+ T-cell tolerance by cross-presentation of self antigens. Immunol Rev 1998; 165: 267-77.
139. Lee MS, Sawyer S, Arnush M, Krahl T, von Herrath M, Oldstone MA, et al. Transforming growth factor-beta fails to inhibit allograft rejection or virus-induced autoimmune diabetes in transgenic mice. Transplantation 1996; 61: 1112-5.
140. von Herrath MG, Yokoyama M, Dockter J, Oldstone MB, Whitton JL. CD4-deficient mice have reduced levels of memory cytotoxic T lymphocytes after immunization and show diminished resistance to subsequent virus challenge. J Virol 1996; 70: 1072-9.
141. Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996; 17: 138-46.
142. Sad S, Kagi D, Mosmann TR. Perforin and Fas killing by CD8+ T cells limits their cytokine synthesis and proliferation. J Exp Med 1996; 184: 1543-7.
143. Barone KS, Jain SL, Michael JG. Effect of in vivo depletion of CD4+ and CD8+ cells on the induction and maintenance of oral tolerance. Cell Immunol 1995; 163: 19-29.
144. Bendelac A, Rivera MN, Park SH, Roark JH. Mouse CD1-specific NK1 T cells: development, specificity, and function. Annu Rev Immunol 1997; 15: 535-62.
145. Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L. NKT cells: what's in a name? Nat Rev Immunol 2004; 4: 231-7.
146. Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol 2007; 25: 297-336.
147. Tsuji M. Glycolipids and phospholipids as natural CD1d-binding NKT cell ligands. Cell Mol Life Sci 2006; 63: 1889-98.
148. Van Kaer L. Natural killer T cells as targets for immunotherapy of autoimmune diseases. Immunol Cell Biol 2004; 82: 315-22.
149. Burdin N, Brossay L, Kronenberg M. Immunization with alpha-galactosylceramide polarizes CD1-reactive NK T cells towards Th2 cytokine synthesis. Eur J Immunol 1999; 29: 2014-25.
150. Eberl G, MacDonald HR. Rapid death and regeneration of NKT cells in anti-CD3epsilon- or IL-12-treated mice: a major role for bone marrow in NKT cell homeostasis. Immunity 1998; 9: 345-53.
151. Laloux V, Beaudoin L, Ronet C, Lehuen A. Phenotypic and functional differences between NKT cells colonizing splanchnic and peripheral lymph nodes. J Immunol 2002; 168: 3251-8.
152. Matsuda JL, Naidenko OV, Gapin L, Nakayama T, Taniguchi M, Wang CR, et al. Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J Exp Med 2000; 192: 741-54.
153. Osman Y, Kawamura T, Naito T, Takeda K, Van Kaer L, Okumura K, et al. Activation of hepatic NKT cells and subsequent liver injury following administration of alpha-galactosylceramide. Eur J Immunol 2000; 30: 1919-28.
154. Taniguchi M, Nakayama T. Recognition and function of Valpha14 NKT cells. Semin Immunol 2000; 12: 543-50.
155. Gansert JL, Kiessler V, Engele M, Wittke F, Rollinghoff M, Krensky AM, et al. Human NKT cells express granulysin and exhibit antimycobacterial activity. J Immunol 2003; 170: 3154-61.
156. Carnaud C, Lee D, Donnars O, Park SH, Beavis A, Koezuka Y, et al. Cutting edge: Cross-talk between cells of the innate immune system: NKT cells rapidly activate NK cells. J Immunol 1999; 163: 4647-50.
157. Kitamura H, Iwakabe K, Yahata T, Nishimura S, Ohta A, Ohmi Y, et al. The natural killer T (NKT) cell ligand alpha-galactosylceramide demonstrates its immunopotentiating effect by inducing interleukin (IL)-12 production by dendritic cells and IL-12 receptor expression on NKT cells. J Exp Med 1999; 189: 1121-8.
158. Hermans IF, Silk JD, Gileadi U, Salio M, Mathew B, Ritter G, et al. NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J Immunol 2003; 171: 5140-7.
159. Van Kaer L. NKT cells: T lymphocytes with innate effector functions. Curr Opin Immunol 2007; 19: 354-64.
160. Cui J, Watanabe N, Kawano T, Yamashita M, Kamata T, Shimizu C, et al. Inhibition of T helper cell type 2 cell differentiation and immunoglobulin E response by ligand-activated Valpha14 natural killer T cells. J Exp Med 1999; 190: 783-92.
161. Singh N, Hong S, Scherer DC, Serizawa I, Burdin N, Kronenberg M, et al. Cutting edge: activation of NK T cells by CD1d and alpha-galactosylceramide directs conventional T cells to the acquisition of a Th2 phenotype. J Immunol 1999; 163: 2373-7.
162. Zigmond E, Preston S, Pappo O, Lalazar G, Margalit M, Shalev Z, et al. Beta-glucosylceramide: a novel method for enhancement of natural killer T lymphoycte plasticity in murine models of immune-mediated disorders. Gut 2007; 56: 82-9.
163. Godfrey DI, Kronenberg M. Going both ways: immune regulation via CD1d-dependent NKT cells. J Clin Invest 2004; 114: 1379-88.
164. Eberl G, Brawand P, MacDonald HR. Selective bystander proliferation of memory CD4+ and CD8+ T cells upon NK T or T cell activation. J Immunol 2000; 165: 4305-11.
165. Nishimura T, Kitamura H, Iwakabe K, Yahata T, Ohta A, Sato M, et al. The interface between innate and acquired immunity: glycolipid antigen presentation by CD1d-expressing dendritic cells to NKT cells induces the differentiation of antigen-specific cytotoxic T lymphocytes. Int Immunol 2000; 12: 987-94.
166. Van Kaer L. Regulation of immune responses by CD1d-restricted natural killer T cells. Immunol Res 2004; 30: 139-53.
167. Ilan Y, Ohana M, Pappo O, Margalit M, Lalazar G, Engelhardt D, et al. Alleviation of acute and chronic graft-versus-host disease in a murine model is associated with glucocerebroside-enhanced natural killer T lymphocyte plasticity. Transplantation 2007; 83: 458-67.
168. Margalit M, Ilan Y. Induction of immune tolerance: a role for Natural killer T lymphocytes? Liver Int 2005; 25: 501-4.
169. Margalit M, Israeli E, Shibolet O, Zigmond E, Klein A, Hemed N, et al. A double-blind clinical trial for treatment of Crohn's disease by oral administration of Alequel, a mixture of autologous colon-extracted proteins: a patient-tailored approach. Am J Gastroenterol 2006; 101: 561-8.
170. Trop S, Samsonov D, Gotsman I, Alper R, Diment J, Ilan Y. Liver-associated lymphocytes expressing NK1.1 are essential for oral immune tolerance induction in a murine model. Hepatology 1999; 29: 746-55.
171. Ilan Y, Weksler-Zangen S, Ben-Horin S, Diment J, Sauter B, Rabbani E, et al. Treatment of experimental colitis by oral tolerance induction: a central role for suppressor lymphocytes. Am J Gastroenterol 2000; 95: 966-73.
172. Gotsman I, Shlomai A, Alper R, Rabbani E, Engelhardt D, Ilan Y. Amelioration of immune-mediated experimental colitis: tolerance induction in the presence of preexisting immunity and surrogate antigen bystander effect. J Pharmacol Exp Ther 2001; 297: 926-32.
173. Shibolet O, Kalish Y, Klein A, Alper R, Zolotarov L, Thalenfeld B, et al. Adoptive transfer of ex vivo immune-programmed NKT lymphocytes alleviates immune-mediated colitis. J Leukoc Biol 2004; 75: 76-86.
174. Margalit M, Shibolet O, Klein A, Elinav E, Alper R, Thalenfeld B, et al. Suppression of hepatocellular carcinoma by transplantation of ex vivo immune-modulated NKT lymphocytes. Int J Cancer 2005; 115: 443-9.
175. Shibolet O, Alper R, Zlotogarov L, Thalenfeld B, Engelhardt D, Rabbani E, et al. NKT and CD8 lymphocytes mediate suppression of hepatocellular carcinoma growth via tumor antigen-pulsed dendritic cells. Int J Cancer 2003; 106: 236-43.
176. Shibolet O, Alper R, Zlotogarov L, Thalenfeld B, Engelhardt D, Rabbani E, et al. Suppression of hepatocellular carcinoma growth via oral immune regulation towards tumor-associated antigens is associated with increased NKT and CD8+ lymphocytes. Oncology 2004; 66: 323-30.
177. Ilan Y. Immune downregulation leads to upregulation of an antiviral response: a lesson from the hepatitis B virus. Microbes Infect 2002; 4: 1317-26.
178. Shibolet O, Alper R, Avraham Y, Berry EM, Ilan Y. Immunomodulation of experimental colitis via caloric restriction: role of Nk1.1+ T cells. J Clin Immunol 2002; 105: 48-56.
179. Trop S, Ilan Y. NK 1.1+ T cell: a two-faced lymphocyte in immune modulation of the IL-4/IFN-gamma paradigm. J Clin Immunol 2002; 22: 270-80.
180. Gotsman I, Beinart R, Alper R, Rabbani E, Engelhardt D, Ilan Y. Induction of oral tolerance towards hepatitis B envelope antigens in a murine model. Antiviral Res 2000; 48: 17-26.
181. Margalit M, Ilan Y. Oral immune regulation: a novel method for modulation of anti-viral immunity. J Clin Virol 2004; 31 Suppl 1: S63-8.
182. Israeli E, Goldin E, Shibolet O, Klein A, Hemed N, Engelhardt D, et al. Oral immune regulation using colitis extracted proteins for treatment of Crohn's disease: results of a phase I clinical trial. World J Gastroenterol 2005; 11: 3105-11.
183. Israeli E, Safadi R, Melhem A, Pappo O, Shibolet O, Klein A, et al. Induction of oral immune regulation towards liver-extracted proteins for treatment of chronic HBV and HCV hepatitis: results of a phase I clinical trial. Liver Int 2004; 24: 295-307.
184. Safadi R, Israeli E, Papo O, Shibolet O, Melhem A, Bloch A, et al. Treatment of chronic hepatitis B virus infection via oral immune regulation toward hepatitis B virus proteins. Am J Gastroenterol 2003; 98: 2505-15.
185. Nowak M, Stein-Streilein J. Invariant NKT cells and tolerance. Int Rev Immunol 2007; 26: 95-119.
186. La Cava A, Van Kaer L, Fu Dong S. CD4+CD25+ Tregs and NKT cells: regulators regulating regulators. Trends Immunol 2006; 27: 322-7.
187. Fujii S, Shimizu K, Hemmi H, Steinman RM. Innate Valpha14(+) natural killer T cells mature dendritic cells, leading to strong adaptive immunity. Immunol Rev 2007; 220: 183-98.
188. Jiang S, Lechler RI, He XS, Huang JF. Regulatory T cells and transplantation tolerance. Hum Immunol 2006; 67: 765-76.
189. Tupin E, Kinjo Y, Kronenberg M. The unique role of natural killer T cells in the response to microorganisms. Nat Rev Microbiol 2007; 5: 405-17.
190. Dougan SK, Kaser A, Blumberg RS. CD1 expression on antigen-presenting cells. Curr Top Microbiol Immunol 2007; 314: 113-41.
191. Pabst O, Bernhardt G, Forster R. The impact of cell-bound antigen transport on mucosal tolerance induction. J Leukoc Biol 2007; 82: 795-800.
192. Niess JH, Reinecker HC. Dendritic cells: the commanders-in-chief of mucosal immune defenses. Curr Opin Gastroenterol 2006; 22: 354-60.
193. Kelsall BL, Leon F. Involvement of intestinal dendritic cells in oral tolerance, immunity to pathogens, and inflammatory bowel disease. Immunol Rev 2005; 206: 132-48.
194. Alpan O, Bachelder E, Isil E, Arnheiter H, Matzinger P. 'Educated' dendritic cells act as messengers from memory to naive T helper cells. Nat Immunol 2004; 5: 615-22.
195. Nowak M, Kopp F, Roelofs-Haarhuis K, Wu X, Gleichmann E. Oral nickel tolerance: Fas ligand-expressing invariant NK T cells promote tolerance induction by eliciting apoptotic death of antigen-carrying, effete B cells. J Immunol 2006; 176: 4581-9.
196. Rodrigues CM, Martins-Filho OA, Vaz NM, Carvalho CR. Systemic effects of oral tolerance on inflammation: mobilization of lymphocytes and bone marrow eosinopoiesis. Immunology 2006; 117: 517-25.
197. da Silva AC, Silva MF, Bianchi C, Ribeiro RC, Nobrega A, Sant'anna O. Is oral tolerance correlated with IgE levels and mast cell numbers? Ann N Y Acad Sci 2004; 1029: 394-7.
198. Elson CO, Cong Y, McCracken VJ, Dimmitt RA, Lorenz RG, Weaver CT. Experimental models of inflammatory bowel disease reveal innate, adaptive, and regulatory mechanisms of host dialogue with the microbiota. Immunol Rev 2005; 206: 260-76.
199. Coombes JL, Robinson NJ, Maloy KJ, Uhlig HH, Powrie F. Regulatory T cells and intestinal homeostasis. Immunol Rev 2005; 204: 184-94.
200. Perera L, Shao L, Patel A, Evans K, Meresse B, Blumberg R, et al. Expression of nonclassical class I molecules by intestinal epithelial cells. Inflamm Bowel Dis 2007; 13: 298-307.