Basic mechanisms and clinical implications of oral tolerance

Current Opinion in Gastroenterology

Volumn 15, Issue 6, 1999, Pages 546-556

  Mowat, Allan Mcl ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 10; INTERLEUKIN 4; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIGEN PRESENTING CELL; ARTICLE; AUTOIMMUNITY; CLONAL ANERGY; CONTROLLED STUDY; FOOD POISONING; IMMUNOLOGICAL TOLERANCE; IMMUNOPATHOLOGY; MOUSE; NONHUMAN; REGULATORY MECHANISM; SUPPRESSOR CELL;

EID: 0032707194     PISSN: 02671379     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001574-199911000-00016     Document Type: Article

References (100)

1. Mowat AM: The regulation of immune responses to dietary protein antigens. Immunol Today 1987, 8:93-98.
2. Duchmann R, Kaiser I, Hermann E, Mayet W, Ewe K, Meyer zum Büschenfelde KH: Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin Exp Immunol 1995, 102:448-455.
3. Duchmann R, Schmitt E, Knolle P, Meyer zum Büschenfelde KH, Neurath M: Tolerance towards resident intestinal flora in mice is abrogated in experimental colitis and restored by treatment with interleukin-10 or antibodies to interleukin-12. Eur J Immunol 1996, 26:934-938.
4. Macpherson AJ, Maloy KJ, Bjarnason I: Intolerance of the dirty intestine. Gut 1999, 44:774-775.
5. Weiner HL: Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today 1997, 18:335-343.
6. Mowat AM, Lamont AG, Bruce MG: A genetically determined lack of oral tolerance to ovalbumin is due to failure of the immune system to respond to intestinally derived tolerogen. Eur J Immunol 1987, 17:1673-1676.
7. Mowat AM, Weiner HL: Oral tolerance: basic mechanisms and clinical implications. In Handbook of Mucosal Immunology, edn 2. Edited by Ogra PL, Mestecky J, Lamm ME, Strober W, McGhee JR, Bienenstock J. San Diego: Academic Press; 1999:587-617.
8. Chen Y, Kuchroo VK, Inobe J-I, Hafler DA, Weiner HL: Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis. Science 1994, 265:1237-1240.
9. Khoury SJ, Hancock WW, Weiner HL: Oral tolerance to myelin basic protein and natural recovery from experimental autoimmune encephalomyelitis are associated with downregulation of inflammatory cytokines and differential upregulation of transforming growth factor β, interleukin 4, and prostaglandin E expression in the brain. J Exp Med 1992, 176:1355-1364.
10. Weiner HL, Friedman A, Miller A, Khoury SJ, Al-Sabbagh A, Santos L, et al.: Oral tolerance: immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens. Annu Rev Immunol 1994, 12:809-838.
11. Melamed D, Friedman A: Direct evidence for anergy in T lymphocytes tolerized by oral administration of ovalbumin. Eur J Immunol 1993, 23:935-942.
12. Strobel C, Mowat AM, Ferguson A: Prevention of oral tolerance induction to ovalbumin and enhanced antigen presentation during a graft-versus-host reaction in mice. Immunology 1985, 56:57-64.
13. Zhang Z, Michael JG. Orally inducible immune unresponsiveness is abrogated by IFNγ treatment. J Immunol 1990, 144:4163-4165.
14. Gilbert KM, Weigle WO: B cell presentation of a tolerogenic signal to Th clones. Cell Immunol 1992, 139:58.
15. Fuchs EJ, Matzinger P: B cells turn off virgin but not memory T cells. Science 1992, 258:1156-1159.
16. Eynon EE, Parker DC: Small B cells as antigen-presenting cells in the induction of tolerance to soluble protein antigens. J Exp Med 1992, 175:131-138.
17. Sanderson I, Ouellette AJ, Carter EA, Walker WA, Harmatz PR: Differential regulation of B7 mRNA in enterocytes and lymphoid cells. Immunology 1993. 79:434-438.
18. Hershberg RM, Framson PE, Cho DH, Lee LY, Kovats S, Beitz J, et al.: Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing. J Clin Invest 1997, 100:204-215.
19. Yoshida H, Hachimura S, Hirahara K, Hisatsune T, Shiraishi A, Kaminogawa S: Induction of oral tolerance in splenocyte-reconstituted SCID mice. Clin Immunol Immunopathol 1998, 87:282-291.
20. Banchereau J, Steinman RL: Dendritic cells and the control of immunity. Nature 1998, 392:245-252.
21. Finkelman FD, Lees A, Birnbaum R, Gause WC, Morris SC: Dendritic cells can present antigen in vivo in a tolerogenic or immunogenic fashion. J Immunol 1996, 157:1406-1414.
22. Steptoe RJ, Thomson AW: Dendritic cells and tolerance induction. Clin Exp Immunol 1996, 105:397-402.
23. Viney JL, Mowat AM, O'Malley JM, Williamson E, Fanger N: Expanding dendritic cells in vivo enhances the induction of oral tolerance. J Immunol 1998, 160:5815-5825. In this paper, administration of flt3L to mice led to increased numbers of DCs with a resting phenotype in the intestine and elsewhere. In parallel, there was enhancement of susceptibility to oral tolerance.
24. Maraskovsky E, Brasel K, Teepe M, Roux ER, Lyman SD, Shortman K, McKenna HJ: Dramatic increase in the number of functionally mature dendritic cells in mice treated with flt3 ligand: multiple dendritic cell subpopulations identified. J Exp Med 1996, 184:1953-1962.
25. Williamson E, O'Malley JM, Viney JL: Defining the role of dendritic cells in oral tolerance induction by visualizing the T cell response elicited by oral administration of soluble protein antigen. Immunology, 97:565-572.
26. Williamson E, Westrich GM, Viney JL: Modulating dendritic cells to optimize mucosal immunization protocols. J Immunol, In press.
27. Stampfli MR, Wiley RE, Neigh GS, Gajewska BU, Lei XF, Snider DP, et al.: GM-CSF transgene expression in the airway allows aerosolized ovalbumin to induce allergic sensitization in mice. J Clin Invest 1998, 102:1704-1714.
28. Stumbles PA, Thomas JA, Pimm CL, Lee PT, Venaille TJ, Proksch S, Holt PG: Resting respiratory tract dendritic cells preferentially stimulate helper cell type 2 (Th2) responses and require obligatory cytokine signals for induction et Th1 immunity. J Exp Med 1998, 188:2019-2031. This interesting, novel study directly explores the nature of DCs isolated from the respiratory tract of mice. It shows how the activation status of mucosal DCs can be modulated by inflammatory signals, and it describes the immunologic consequences.
29. Thompson CB, Allison JP: The emerging role of CTLA-4 as an immune attentuator. Immunity 1997, 7:445-450.
30. Perez VL, Parijs LV, Biuckians A, Zheng XX, Strom TB, Abbas AK: Induction of peripheral T cell tolerance in vivo requires CTLA-4 engagement. Immunity 1997, 6:411-417.
31. Samoilova EB, Horton JL, Zhang H, Khoury SJ, Weiner HL, Chen Y: CTLA-4 is required for the induction of high dose oral tolerance. Int Immunol 1998, 10:491-498.
32. Oosterwegel MA, Greenwald RJ, Mandelbrot DA, Lorsbach RB, Sharpe AH: CTLA-4 and T cell activation. Curr Opin Immunol 1999, 11:294-300. An up-to-date, highly readable review of the biology of CTLA-4 and its role in regulating immune responses.
33. Brunner MC, Chambers CA, Chan FK, Hanke J, Winoto A, Allison JP: CTLA-4-mediated inhibition of early events of T cell proliferation. J Immunol 1999, 162:5813-5820.
34. + T cells. J Exp Med 1996, 188:1849-1857. This paper presents evidence that ligation of CTLA-4 may not only be important for the induction of T-cell anergy but may also regulate production of TGF-β.
35. Wu X-M, Nakashima M, Watanabe T: Selective suppression of antigen-specific th2 cells by continuous micro-dose oral tolerance. Eur J Immunol 1998, 28:134-142.
36. Lenschow DJ, Walunas TL, Bluestone JA: CD28/B7 system of 1 cell costimulation. Ann Rev Immunol 1996, 14:233-258.
37. McAdam AJ, Schweitzer AN, Sharpe AH: The role of B7 co-stimulation in activation and differentiation of CD4+ and CD8+ T cells. Immunol Rev 1998, 165:231-247.
38. Kuchroo VK, Das JA, Brown AM, Zarnvil SS, Sobel RA, Weiner HL, et al.: B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 1995, 80:707-718.
39. Schweitzer AN, Borriello F, Wong RC, Abbas AK, Sharpe AH: Role of costimulators in T cell differentiation: studies using antigen-presenting cells lacking expression of CD80 or CD86. J Immunol 1997, 158:2713-2722.
40. De Saint-Vis B, Fugier-Vivier I, Massacrier C, Gaillard C, Vanbervliet B, Ait-Yahia S, et al.: The cytokine profile expressed by human dendritic cells is dependent on cell subtype and mode of activation. J Immunol 1998, 160:1666-1676.
41. Durie FH, Foy TM, Masters SR, Laman JD, Noelle RJ: The role of CD40 in the regulation of humoral and cell mediated immunity. Immunol Today 1994, 15:406-411.
42. Buhlmann JE, Foy TM, Aruffo A, Crassi KM, Ledbotter JA, Green WR, et al.: In the absence of a CD40 signal, B cells are tolerogenic. Immunity 1995, 2:645-653.
43. Stuber E, Strober W, Neurath M: Blocking the CD40L-CD40 interaction in vivo specifically prevents the priming of T helper 1 cells through the inhibition of interleukin 12 secretion. J Exp Med 1996, 183:693-698.
44. Grewal IS, Flavell RA: CD40 and CD154 in cell-mediated immunity. Annu Rev Immunol 1998, 16:111-135.
45. Kweon M-N, Fujihashi K, Wakatsuki Y, Yamamoto M, McGhee JR, Kiyono HR: Mucosally induced systemic T cell unresponsiveness to ovalbumin requires CD4O ligand-CD40 interactions. J Immunol 1999, 162:1904-1909.
46. van Kooten C, Gerritsma JS, Paape ME, van Es LA, Banchereau J, Daha MR: Possible role for CD40-CD40L in the regulation of interstitial infiltration in the kidney. Kidney Int 1987, 51:711-721.
47. Hess S, Engelmann H: A novel function of CD40: induction of cell death in transformed cells. J Exp Med 1996, 183: 159-167.
48. Mueller DL, Jenkins MK, Schwartz RH: Clonal expansion versus functional clonal inactivation: a costimulatory signalling pathway determines the outcome of T cell antigen receptor occupancy. Annu Rev Immunol 1989, 7:445-480.
49. Pape KA, Merica R, Mondino A, Khoruts A, Jenkins MK: Direct evidence that functionally impaired CD4+ T cells persist in vivo following induction of peripheral tolerance. J Immunology 1998, 160:4719-4729.
50. Kearney ER, Papa KA, Loh DY, Jenkins MK: Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo. Immunity 1994, 1;327-339.
51. + T cells. The data show clearly how T cells are activated rapidly after feeding of soluble antigen, and some of the anatomic factors are described.
52. Van Houten N, Blake SF: Direct measurement of anergy of antigen-specific T cells following oral tolerance induction. J Immunol 1996, 167:1337-1341.
53. Chen Y, Inobe J-I, Weiner HL: Inductive events in oral tolerance in the TcR transgenic adoptive transfer model. Cell Immunol 1997, 178:62-68.
54. + T cells. Activation is followed by unresponsiveness in a wide variety of lymphoid tissues, and antigen-loaded APCs are identified in the spleen.
55. Chen Y, Inobe J-I, Marks R, Gonnella P, Kuchroo VK, Weiner HL: Peripheral deletion of antigen-reactive T cells in oral tolerance. Nature 1995, 376;177-180.
56. Marth T, Strober W, Kelsall BL: High dose oral tolerance in ovalbumin TcR-transgenic mice: systemic neutralisation of interleukin 12 augments TGF-β secretion and T cell apoptosis. J Immunol 1996, 157:2348-2357.
57. Pape KA, Kearney ER, Khoruts A, Mondino A, Merica R, Chen Z-M, et al.: Use of adoptive transfer of T-cell-antigen-receptor-transgenic T cells for the study of T-cell activation in vive. Immunol Rev 1997, 156:67-78.
58. Gonnella PA, Chen Y, Inobe J-I, Komagata Y, Quartulli M, Weiner HL: In situ immune response in gut-associated lymphoid tissue (GALT) following oral antigen in TCR-transgenic mice. J Immunol 1998, 160:4708-4718.
59. Spahn TW, Koni PA, Marino MW, Rennert P, Fontana A, Weiner HL: A critical role for the gut-associated lymphatic tissue in the induction of oral tolerance. Immunol Lett 1999, 69:86A.
60. Wolvers DAW, Coenen-De Roo CJJ. Mebius RE, Van Der Cammen MJF, Tirion F, Miltenburg AMM, Kraal G: Intranasally induced immunological tolerance is determined by characteristics of the draining lymph nodes: studies with OVA and human cartilage gp39. J Immunol 1999, 162:1994-1998. This intriguing study uses an elegant surgical approach to show that the lymph nodes draining the upper respiratory tract are essential for the induction of tolerance by intranasal instillation of antigen. These nodes cannot be replaced by other, peripheral lymph nodes.
61. Daynes RA, Araneo BA, Dowell TA, Huang K, Dudley D: Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function. J Exp Med 1990, 171:979-996.
62. Bruce MG, Ferguson A: Oral tolerance to ovalbumin in mice: studies of chemically modified and of "biologically filtered" antigen. Immunology 1986, 57:627-630.
63. Peng H-J, Turner MW, Strobel S: The generation of a 'tolerogen' after the ingestion of ovalbumin is time-dependent and unrelated to serum levels of immunoreactive antigen. Clin Exp Immunol 1990, 81:510-515.
64. Grdic D, Hornquist E, Kjerrulf M, Lycke N: Lack of local suppression in orally tolerant CD8-deficient mice reveals a critical regulatory role of CD8+ T cells in the normal gut mucosa. J Immunol 1998, 160:754-762. This paper presents evidence that feeding antigen can suppress both local and systemic immunity and that these immunities may be regulated by different mechanisms.
65. Lundin BS, Karlsson MR, Svensson LA, Hanson LA, Dahlgren UI, Telemo E: Active suppression in orally tolerized rats coincides with in situ transforming growth factor-β (TGF-β) expression in the draining lymph nodes. Clin Exp Immunol 1999, 116:181-187.
66. Neurath MF, Fuss I, Kelsall BL, Presky DH, Waegell W, Strober W: Experimental granulomatous colitis in mice is abrogated by induction of TGF-β-mediated oral tolerance. J Exp Med 1996, 183:2605-2616.
67. Inobe J-I, Slavin AJ, Komagata Y, Chen Y, Liu L, Weiner HL: IL-4 is a differentiation factor for transforming growth factor-β secreting Th3 cells and oral administration of IL-4 enhances oral tolerance in experimental allergic encephalomyelitis. Eur J Immunol 1998, 28:2780-2790. This paper describes the role of interleukin-4 as an in vivo growth factor in the development of regulatory T cells that produce TGF-β.
68. Haneda K, Sano K, Tamura G, Sato T, Habu S, Shirato K: TGF-β induced by oral tolerance ameliorates experimental tracheal eosinophilia. J Immunol 1997, 159:4484-4490.
69. Grdic D, Smith RE, Donachie AM, Kjerrulf M, Hörnqusit E, Mowat AM, Lycke N: The mucosal adjuvant effect of cholera toxin and ISCOMS differ in their requirement for IL-12, indicating different pathways of action. Eur J Immunol 1999, 29:1774-1784.
70. + T cells.
71. Barone KS, Tolarova DD, Ormsby I, Doetschman T, Michael JG; Induction of oral tolerance in TGF-β1 null mice. J Immunol 1998, 161:154-160. This was the first study to examine oral tolerance in genetically defective TGF-β KO mice. It does not provide conclusive evidence that TGF-β is essential for oral tolerance, but it suggests at least a contributory role.
72. Karpus WJ, Kennedy KJ, Kunkel SL, Lukacs NW: Monocyte chemotactic protein 1 regulates oral tolerance induction by inhibition of T helper cell 1-related cytokines. J Exp Med 1998, 187:733-741.
73. Yoshino S: Treatment with anti-IL4 monoclonal antibody blocks suppression of collagen-induced arthritis in mice by oral administration of type II collagen. J Immunol 1998, 160:3067-3071.
74. Yoshino S, Yoshino J: Effect of a monoclonal antibody against interleukin-4 on suppression of antigen-induced arthritis in mice by oral administration of the inducing antigen. Cell Immunol 1998, 187:139-144.
75. Garside P, Steel M, Worthey EA, Satoskar A, Alexander J, Bluethmann H, et al.: Th2 cells are subject to high dose oral tolerance and are not essential for its induction. J Immunol 1995, 154:5649-5655.
76. Shi HN, Grusby MJ, Nagler-Anderson C: Orally induced peripheral nonresponsiveness is maintained in the absence of functional Th1 or Th2 cells. J Immunol 1999, 162:5143-5148.
77. Groux H, O'Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, Roncarlo MG: A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 1997, 389:737-742.
78. Aroeira LS, Cardillo F, De-Albuquerque D, Vaz NM, Mengel J: Anti-IL-10 treatment does not block either the induction or the maintenance of orally induced tolerance to OVA. Scand J Immunol 1995, 44:319-323.
79. Ke Y, Pearce K, Lake JP, Ziegler HK, Kapp JA: γδ T lymphocytes regulate the induction of oral tolerance. J Immunol 1997, 158;3610-3618.
80. Thurau SR, Chan C-C, Nusenblatt RB, Caspi RR: Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis: induction of protective tolerance in primed animals. Clin Exp Immunol 1997, 109:370-376.
81. Mengel J, Cardillo F, Aroeira LS, Williams O, Russo M, Vaz NM: Anti-gammadelta T cell antibody blocks the induction and maintenance of oral tolerance to ovalbumin in mice. Immunol Lett 1995, 48:97-102.
82. Wildner G, Hünig T, Thurau SR: Orally induced, peptide-specific γ/δ TcR+ cells suppress experimental autoimmune uveitis. Eur J Immunol 1996, 26:2140-2148.
83. McMenamin C, McKersey M, Kuhnlein P, Hunig T, Holt PG: γδ T cells down-regulate primary lgE responses in rats to inhaled soluble protein antigens. J Immunol 1995, 154:4390-4394.
84. Hoyne GF, Thomas WR: T-cell responses to orally administered antigens. Study of the kinetics of lymphokine production after single and multiple feeding. Immunology 1995, 84:304-309.
85. Strober W, Kelsall B, Fuss I, Marth T, Ludviksson B, Ehrhardt R, Neurath M: Reciprocal IFN-γ and TGF-β responses regulate the occurrence of mucosal inflammation. Immunol Today 1997, 18:61-64.
86. Kweon M-N, Fujihashi K, VanCott JL, Higuchi K, Yamamoto M, McGhee JR, Kiyono H: Lack of orally induced systemic unresponsiveness in IFN-γ knockout mice. J Immunol 1998, 160:1687-1693.
87. Kjerrulf M, Grdic D, Ekman L, Schön K, Vajdy M, Lycke NY: Interferon-γ receptor-deficient mice exhibit impaired gut mucosal immune responses but intact oral tolerance. Immunology 1997, 92:60-68.
88. Mowat AM, Steel M, Leishman AJ, Garside P: Normal induction of oral tolerance in the absence of a functional IL 12 dependent γ interferon signalling pathway. J Immunol, In press.
89. Boyaka P, Marinaro M, Jackson RJ, Menon S, Kiyono H, Jirillo E, McGhee JR: IL-12 is an effective adjuvant for induction of mucosal immunity. J Immunol 1999, 162:122-128.
90. + T cells. These important studies show how T cells can regulate the behavior of other T cells via cognate effects on APCs.
91. Lanoue A, Bona C, von Boehmer H, Sarukhan A: Conditions that induce tolerance in mature CD4+ T cells. J Exp Med 1997, 185:405-414.
92. Ryan KR, Evavold BD: Persistence of peptide-induced CD4+ T cell energy in vitro. J Exp Med 1998, 187:89-96.
93. Buer J, Lanoue A, Franzke A, Garcia C, von Boehmer H, Sarukhan H: Interleukin 10 secretion and impaired effector function of major histocompatibility complex class II-restricted T cells energized in vivo. J Exp Med 1998, 187:177-183.
94. Hirahara K, Hisatsune T, Nishijima K-I, Kato H, Shiho O, Kaminogawa S: CD4+ T cells anergized by high dose feeding establish oral tolerance to antibody responses when transferred in SCID and nude mice. J Immunol 1995, 154:6238-6245.
95. Lombardi G, Arnold K, Uren J, Marelli-Berg F, Hargreaves R, Imami N, et al.: Antigen presentation by interferon-y-treated thyroid follicular cells inhibits interleukin-2 (IL-2) and supports IL-4 production by B7-dependent human T cells. Eur J Immunol 1997, 27:62-71.
96. Cauley LS, Cauley KA, Shub F, Huston G, Swain SL: Transferable energy: superantigen treatment induces CD4+ T cell tolerance that is reversible and requires CD4-CD8-cells and interferon γ. J Exp Med 1997, 186:71-81.
97. Taams LS, van Rensen AJML, Poelen MCM, van Els CACM, Besseling AC, Wagenaar JPA, et al.: Anergic T cells actively suppress T cell responses via the antigen-presenting cell. Eur J Immunol 1998, 28:2902-2912. This novel and interesting report shows that T cells that are apparently anergic can actively suppress the functions of other T cells. This suppression requires a cognate interaction between the anergic T cell and an APC so that the APC is "deactivated" and cannot present antigen effectively to third-party T cells.
98. 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, 188:287-296.
99. Takahashi T, Kuniyasu Y, Toda M, Sakaguchi N, Itoh M, Iwata M, et al.: Immunologic self-tolerance maintained by CD25+CD4+ naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 1998, 10:1969-1980.
100. Dahlman-Hoglund A, Ahlstedt S, Hanson LA, Dahlgren U. Telemo E: Different expression of IL-2 receptor alpha-chain on a lamina propria T cell population and goblet cells in rats orally tolerized or sensitized to ovalbumin (OA) after colonization with an OA-producing Escherichia coli. Clin Exp Immunol 1996, 106:534-540.