Mechanisms of oral tolerance

Critical Reviews in Immunology

Volumn 17, Issue 2, 1997, Pages 119-137

  Garside, Paul ^a   Mowat, Allan McI ^a  

^a UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

anergy; co stimulation; cytokines; deletion; mucosal; oral tolerance; suppression; T cells; therapy

Indexed keywords

CD8 ANTIGEN; GAMMA INTERFERON; INTERLEUKIN 10; INTERLEUKIN 4; TRANSFORMING GROWTH FACTOR BETA;

ANTIGEN SPECIFICITY; CONTROLLED STUDY; FOOD ALLERGY; HYPERSENSITIVITY REACTION; IMMUNE RESPONSE; IMMUNOLOGICAL TOLERANCE; IMMUNOREGULATION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW;

EID: 0030942047     PISSN: 10408401     EISSN: None     Source Type: Journal    
DOI: 10.1615/critrevimmunol.v17.i2.10     Document Type: Review

References (130)

1. Mowat, A. McI., Oral tolerance and regulation of immunity to dietary antigens, in Handbook of Mucosal Immunology, Ogra, P. L., Mestecky, J., Lamm, M. E., Strober, W., McGhee, J. R., and Bienenstock, J., Eds., Academic Press, San Diego, CA, 1993, 185.
2. Mowat, A. McI., The regulation of immune responses to dietary protein antigens, Immunol. Today, 8, 93, 1987.
3. 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., Oral tolerance: Immunologic mechanisms and treatment of animal and human organ-specific autoimmune diseases by oral administration of autoantigens, Annu. Rev. Immunol., 12, 809, 1994.
4. Garside, P., Behnke, J. M., and Rose, R. A., Acquired immunity to Ancylostoma ceylanicum in hamsters, Parasite Immunol., 12, 247, 1990.
5. H2 cells are subject to high-dose oral tolerance and are not essential for its induction, J. Immunol., 154, 5649, 1995.
6. Wells, H. G. and Osborne, T. B., The biological reactions of the vegetable proteins. I. Anaphylaxis, J. Infect. Dis., 8, 66, 1911.
7. Stokes, C. R., Miller, B. G., and Bourne, F. J., Animal models of food sensitivity, in Food Allergy and Intolerance, Brostoff, J. and Challacombe, S. J., Eds., Saunders, Eastbourne, 1987, 286.
8. Deplazes, P., Penhale, W. J., Greene, W. K., and Thompson, R. C. A., Effect on humoral tolerance (IgG and IgE) in dogs by oral administration of ovalbumin and Der PI, Vet. Immunol. Immunopath., 45, 361, 1995.
9. Heppell, L. M. and Kilshaw, P. J., Immune responses in guinea pigs to dietary protein. I. Induction of tolerance by feeding ovalbumin, Int. Archs. Allergy Appl. Immunol., 68, 54, 1982.
10. Bhogal, B. S., Karkhanis, Y. D., Bell, M. K., Sanchez, P., Zemcik, B., Siskind, G. W., and Thorbecke, G. J., Production of auto-antiidiotypic antibody during the normal immune response. XII. Enhanced auto-antiidiotypic antibody production as a mechanism for apparent B cell tolerance in rabbits after feeding antigen, Cell. Immunol., 101, 93, 1986.
11. Korenblat, P. E., Rothberg, R. M., Minden, P., and Fair, R. S., Immune responses of human adults after oral and parenteral exposure to bovine serum albumin, J. Allergy, 41, 226, 1968.
12. Husby, S., Mestecky, J., Moldoveanu, Z., Holland, S., and Elson, C. O., Oral tolerance in humans: T cell but not B cell tolerance after antigen feeding, J. Immunol., 12, 809, 1994.
13. Gautam, S. C. and Battisto, J. R., Orally induced tolerance generates an efferently acting suppressor T cell and an acceptor T cell that together down-regulate contact sensitivity, J. Immunol., 135, 2975, 1985.
14. MacDonald, T. T., Immunosuppression caused by antigen feeding. I. Evidence for the activation of a feedback suppressor pathway in the spleen of antigen-fed mice, Eur. J. Immunol., 12, 767, 1982.
15. Sayegh, M. H., Zhang, Z. J., Hancock, W. W., Kwok, C. A., Carpenter, C. B., and Weiner, H. L., Down-regulation of the immune response to histocompatibility antigens and prevention of sensitization by skin allografts by orally administered alloantigen, Transplantation, 53, 163, 1992.
16. Javed, N. H., Gienapp, I. E., Cox, K. L., and Whitacre, C. C., Exquisite peptide specificity of oral tolerance in experimental autoimmune encephalomyelitis, J. immunol., 1599, 1995.
17. Rubin, D., Weiner, H. L., Fields, B. N., and Green, M. I., Immunologic tolerance after oral administration of reovirus: requirement for two viral gene products for tolerance induction, J. Immunol., 127, 1697, 1981.
18. Stokes, C. R., Newby, T. J., Huntley, J. H., Patel, D., and Bourne, F. J., The immune response of mice to bacterial antigens given by mouth, Immunology, 38, 497, 1979.
19. Strobel, S. and Ferguson, A., Immune responses to fed protein antigens in mice. III. Systemic tolerance or priming is related to age at which antigen is first encountered, Pediatr. Res., 18, 588, 1984.
20. Lamont, A. G., Mowat, A. McI., Browning, M. J., and Parrott, D. M. V., Genetic control of oral tolerance to ovalbumin in mice, Immunology, 63, 737, 1988.
21. Lamont, A. G., Gordon, M., and Ferguson, A., Oral tolerance in protein-deprived mice. I. Profound antibody tolerance but impaired DTH tolerance after antigen feeding, Immunology, 61, 333, 1987.
22. Wannemuehler, M. J., Kiyono, H., Babb, J. L., Michalek, S. M., and McGhee, J. R., Lipopolysaccharide (LPS) regulation of the immune response: LPS converts germ-free mice to sensitivity to oral tolerance induction, J. Immunol., 129, 959, 1982.
23. Miller, B. G., Newby, T. J., Stokes, C. R., and Bourne, F. J., Influence of diet on postweaning malabsorption and diarrhoea in the pig, Res. Vet. Sci., 36, 187, 1984.
24. Miller, A., Lider, O., Abramsky, O., and Weiner, H. L., Orally administered myelin basic protein in neonates primes for immune responses and enhances experimental autoimmune encephalomyelitis in adult animals, Eur. J. Immunol., 24, 1026, 1994.
25. McGhee, J. R., Mestecky, J., Dertzbaugh, M. T., Eldridge, J. H., Hirasawa, M., and Kiyono, H., The mucosal immune system: from fundamental concepts to vaccine development, Vaccine, 10, 75, 1992.
26. Holt, P. G. and Sedgwick, Suppression of IgE responses following antigen inhalation: a natural homeostatic mechanism which limits sensitization to aeroallergens, Immunol. Today, 8, 14, 1987.
27. McMenamin, C., Pimm, C., McKersey, M., and Holt, P. G., Regulation of IgE responses to inhaled antigen in mice by antigen-specific γδ T cells, Science, 265, 1869, 1994.
28. McMenamin, C., McKersey, M., Kuhnlein, P., Hunig, T., and Holt, P. G., γδ T cells down-regulate primary IgE responses in rats to inhaled soluble protein antigens, J. Immunol., 154, 4390, 1995.
29. Vaz, N. M., Maia, L. C. S., Hanson, D. G., and Lynch, J. M., Inhibition of homocytotropic antibody responses in adult inbred mice by previous feeding of the specific antigen, J. Allergy Clin. Immunol., 60, 110, 1977.
30. H2 lymphocytes induced by continuous feeding of ovalbumin, 9th International Congress on Immunology, 1995, abstr. 3621.
31. Jarrett, E. E. and Hall, E., The development of IgE-suppressive immunocompetence in young animals: influence of exposure to antigen in the presence or absence of maternal immunity, Immunology, 53, 365, 1984.
32. + T cells are required for the induction of oral tolerance, Int. Immunol., 7, 501, 1995.
33. Desvignes, C., Benoist, C., Mathis, D., and Kaiserlian, D., Oral immunization of MHC-class-II and Ii knock-out mice with DNFB induces specific contact sensitivity, 9th International Congress on Immunology, 1995, Abstr. 3591.
34. Challacombe, S. J. and Tomasi, T. B., Systemic tolerance and secretory immunity after oral immunization, J. Exp. Med., 152, 1459, 1980.
35. MacDonald, T. T., Immunosuppression caused by antigen feeding. II. Suppressor T cells mask Peyer's patch B cell priming to orally administered antigen, Eur. J. Immunol., 13, 138, 1983.
36. Elson, C. O. and Ealding, W., Generalized systemic and mucosal immunity in mice after mucosal stimulation with cholera toxin, J. Immunol., 132, 2736, 1984.
37. Walker, W. A., Role of the mucosal barrier in antigen handling by the gut, in Food Allergy and Intolerance, Brostoff, J. and Challacombe, S. J., Eds., Saunders, Eastbourne, 1987, 209.
38. Stokes, C. R., Swarbrick, E. T., and Soothill, J. F., Genetic differences in immune exclusion and partial tolerance to ingested antigens, Clin. Exp. Immunol., 52, 678, 1983.
39. Kiyono, H., McGhee, J. R., Wannemeuhler, M. J., and Michalek, S. M., Lack of oral tolerance in C3H/ HeJ mice, J. Exp. Med., 155, 605, 1982.
40. Gregerson, D. S., Obritsch, W. F., and Donoso, L. A., Oral tolerance in experimental autoimmune uveoretinitis: distinct mechanisms of resistance are induced by low-versus high-dose feeding protocols, J. Immunol., 151, 5751, 1993.
41. Metcalfe, D. D., Food allergy, in Handbook of Mucosal Immunology, Ogra, P. L., Mestecky, J., Lamm, M. E., Strober, W., McGhee, J. R., and Bienenstock, J., Eds. Academic Press, San Diego, CA, 1993, 493.
42. Lamont, A. G., Mowat, A. McI., and Parrott, D. M. V., Priming of systemic and loval delayed-type hypersensitivity responses by feeding low doses of ovalbumin to mice, Immunology, 66, 595, 1989.
43. Miller, B. G., Whittemore, C. T., Stokes, C. R., and Telemo, E., The effect of delayed weaning on the development of oral tolerance to soya-bean protein in pigs, Br. J. Nutr., 71, 615, 1994.
44. Jarrett, E. E., Perinatal influences on IgE responses, Lancet, 797, 1984.
45. Strobel, S. and Ferguson, A., Persistence of oral tolerance in mice fed ovalbumin is different for humoral and cell-mediated immune responses, Immunology, 60, 317, 1987.
46. Peng, H-J., Turner, M. W., and Strobel, S., Failure to induce tolerance for delayed hypersensitivity to protein antigens in neonatal mice can partially be corrected by spleen cell transfer, Pediatr. Res., 468, 1989.
47. Lamont, A. G., Bruce, M. G., Watret, K. C., and Ferguson, A., Suppression of an established DTH response to ovalbumin in mice by feeding antigen after immunization, Immunology, 64, 135, 1988.
48. Zhang, J. Z., Lee, C. S. Y., Lider, O., and Weiner, H. L., Suppression of adjuvant arthritis in Lewis rats by oral administration of type II collagen, J. Immunol., 145, 2489, 1990.
49. Nussenblatt, R. B., Caspi, R. R., Mahdi, R., Chan, C. C., Roberge, F., Lider, O., and Weiner, H. L., Inhibition of S-antigen induced experimental autoimmune uveoretinitis by oral induction of tolerance with S-antigen, J. Immunol., 144, 1689, 1990.
50. Devey, M. E. and Bleasdale, K., Antigen feeding modifies the course of antigen-induced immune complex disease, Clin. Exp. Immunol., 56, 637, 1984.
51. Muir, A., Schatz, D., and Maclaren, N., Antigen-specific immunotherapy: oral tolerance and subcutaneous immunization in the treatment of insulin-dependent diabetes, Diabetes/Metabolism Rev., 9, 279, 1993.
52. Vives, J., Parks, D. E., and Weigle, W. D., Immunologic unresponsiveness after gastric administration of human γ-globulin: antigen requirements and cellular parameters, J. Immunol., 125, 1811, 1980.
53. Asherson, G. L., Perera, M. A. C. C., and Thomas, W. R., Contact sensitivity and the DNA response in mice to high and low doses of oxazolone: low-dose unresponsiveness following painting and feeding and its prevention by pretreatment with cyclophosphamide, Immunology, 36499, 1979.
54. Chase, M. W. and Battisto, J. R., The duration of dermal sensitization following cellular transfer in guinea pigs, J. Allergy, 26, 83, 1955.
55. Thomas, H. C. and Parrott, D. M. V., Induction of tolerance to a soluble protein antigen by oral administration, Immunology, 27, 631, 1974.
56. Miller, A., Lider, O., and Weiner, H. L., Antigen-driven bystander suppression after oral administration of antigens, J. Exp. Med., 174, 791, 1991.
57. Mattingly, J. A. and Waksman, B. H., Immunologic suppression after oral administration of antigen. I. Specific suppressor cells formed in rat Peyer's patches after oral administration of sheep erythrocytes and their systemic migration, J. Immunol., 121, 1878, 1978.
58. Granstein, R. D. and Greene, M. I., Splenic I-J bearing antigen-presenting cells in activation of suppression: further characterization, Cell Immunol., 91, 12, 1985.
59. Gesualdo, L., Lamm, M. E., and Emanicaptor, S. M., Defective oral tolerance promotes nephritogenesis in experimental IgA nephropathy induced by oral immunization, J. Immunol., 145, 3684, 1990.
60. Mowat, A. McI., Depletion of suppressor T cells by 2′-deoxyguanosine abrogates tolerance in mice fed ovalbumin and permits the induction of intestinal delayed-type hypersensitivity, Immunology, 58, 179, 1986.
61. Miller, A., Lider, O., and Weiner, H. L., Antigen-driven bystander suppression after oral administration of antigens, J. Exp. Med., 174, 791, 1991.
62. + cells mediate active suppression, J. Immunol., 155, 910, 1995.
63. Miller, A., Lider, O., Roberts, A. B., Sporn, M., and Weiner, H. L., Suppressor T cells generated by oral tolerization to myelin basic protein suppress both in vitro and in vivo immune responses by the release of TGF-β following antigen specific triggering, Proc. Natl. Acad. Sci. U.S.A., 89, 421, 1992.
64. Miller, A., Al-Sabbagh, A., Santos, L. M. B., Prabhu Das, M., and Weiner, H. L., Epitopes of myelin basic protein that trigger TGFβ release after oral tolerization are distinct from encephalitogenic epitopes and mediate epitope-driven bystander suppression, J. Immunol., 151, 7307, 1993.
65. Hoyne, G. F., O'Hehir, R. E., Wraith, D. C., Thomas, W. R., and Lamb, J. R., Inhibition of T cell and antibody responses to house dust mite allergen by inhalation of the dominant T cell epitope in naive and sensitized mice, J. Exp. Med., 178, 1783, 1993.
66. Rock, K. L., Rothstein, L., Fleischacker, C., and Gamble, S., Inhibition of class I and class II MHC-restricted antigen presentation by cytotoxic T lymphocytes specific for an exogenous antigen, J. Immunol., 148, 3028, 1992.
67. + cells on the induction and maintenance of oral tolerance, Cell. Immunol., 163, 19, 1995.
68. Lycke, N., Bromander, A., Ekman, L., Grdic, D., Hornquist, E., Kjerrulf, M., Kopf, M., Kosco-Vilbois, M., Schon, K., and Vajdy, M., The use of knock-out mice in studies of induction and regulation of gut mucosal immunity, Mucosal Immunol. Update, 3, 1, 1995.
69. H2 cells: different patterns of lymphokine secretion lead to different functional properties, Ann. Rev. Immunol., 7, 145, 1989.
70. + T cells anergized by high-dose feeding establish oral tolerance to antibody responses when transferred in SCID and nude mice, J. Immunol., 154, 6238, 1995.
71. Chen, Y., Kuchroo, V. K., Inobe, J-I., Hafler, D. A., and Weiner, H. L., Regulatory T cell clones induced by oral tolerance: suppression of autoimmune encephalomyelitis, Science, 265, 1237, 1994.
72. Fishman-Lobell, J., Friedman, A., and Weiner, H. L., Different kinetic patterns of cytokine gene expression in vivo in orally tolerant mice, Eur. J. Immunol., 24, 2720, 1994.
73. Khoury, S. J., Hancock, W. W., and Weiner, H. L., 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., 176, 1355, 1992.
74. Chen, Y., Inobe, J-I., Kuchroo, V. K., Baron, J. L., Janeway, C. A., Jr., and Weiner, H. L., Oral tolerance in myelin basic protein T-cell receptor transgenic mice: suppression of autoimmune encephalomyelitis and dose-dependent induction of regulatory cell, Proc. Natl. Acad. Sci. U.S.A., 388, 1996.
75. Mengel, J., Cardillo, F., Aroeira, I. S., Williams, O., Russo, M., and Vaz, N. M., Anti-gamma delta T cell antibody blocks the induction and maintenance of oral tolerance to ovalbumin in mice, Immunol. Lett., 48, 97, 1995.
76. Lefrancois, L., Basic aspects of intraepithelial lymphocyte immunobiology, in Handbook of Mucosal Immunology, Ogra, P. L., Mestecky, J., Lamm, M. E., Strober, W., McGhee, J. R., and Bienenstock, J., Eds., Academic Press, San Diego, CA, 287.
77. Maloy, K. J., Mowat, A. McI., Zamoyska, R., and Crispe, I. N., Phenotypic heterogeneity of intraepithelial T lymphocytes from mouse small intestine, Immunology, 72, 555, 1991.
78. Burstein, H. J. and Abbas, A. K., In vivo role of interleukin 4 in T cell tolerance induced by aqueous protein antigen, J. Exp. Med., 177, 457, 1993.
79. Fishman-Lobell, J., Kuchroo, V., and Weiner, H. L., Oral tolerance in IL-4 gene disrupted and IL-10 transgenic mice, 9th International Congress of Immunology, 1995, Abstr. number 3579.
80. H1 cells, J. Immunol., 146, 3444, 1991.
81. Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K., and Muller, W., Interleukin-10-deficient mice develop chronic enterocolitis, Cell, 75, 263, 1993.
82. Aroeira, L. S., Cardillo, F., DeAbuquerque, D. A., Vaz, N. M., and Mengel, J., Anti-IL-10 treatment does not block either the induction or the maintenance of orally induced tolerance to OVA, Scand. J. Immunol., 41, 319, 1995.
83. + T-cell-dependent immune deviation resulting in selective suppression of immunoglobulin E production, J. Exp. Med., 178, 889, 1993.
84. Symington, F. W., Lymphotoxin, tumor necrosis factor and gamma interferon are cytostatic for normal human keratinocytes, J. Invest. Dermatol., 92, 798, 1989.
85. Baschieri, S., Lees, R. K., Lussow, A. R., and MacDonald, H. R., Clonal anergy to staphylococcal enterotoxin B in vivo: selective effects on T cell subsets and lymphokines, Eur. J. Immunol., 23, 2661, 1993.
86. + T cells, Eur. J. Immunol., 23, 523, 1993.
87. Mowat, A. McI., Garside, P., Fitton, L. A., Higley, H. R., and Carlino, J. A., Regulatory activity of endogenous and exogenous transforming growth factor β in experimental intestinal immunopathology, Growth Factors, 13, 75, 1996.
88. Roberts, A. B. and Sporn, M. B., The transforming growth factor βs, in Handbook of Experimental Pharmacology, Sporn, M. B. and Roberts, A. B., Eds., Springer-Verlag, New York, 1990, 419.
89. Chen, Y., Inobe, J., Marks, R., Gonnella, P., Kuchroo, V. K., and Weiner, H. L., Peripheral deletion of antigen-reactive T cells in oral tolerance, Nature, 376, 177, 1995.
90. Albina, J. E., Cui, S., Mateo, R. B., and Reichner, J. S., Nitric oxide-mediated apoptosis in murine peritoneal macrophages, J. Immunol., 150, 5080, 1993.
91. Taylor-Robinson, A. W., Liew, F. Y., Severn, A., Xu, D., McSorley, S. J., Garside, P., Padron, J., and Phillips, R. S., Regulation of the immune response by nitric oxide differentially produced by T helper type 1 and T helper type 2 cells, Eur. J. Immunol., 24, 980, 1994.
92. 1 phase of the cell cycle, Immunology, 87, 242, 1996.
93. Hanson, D. G. and Miller, S. D., Inhibition of specific immune responses by feeding protein antigens. V. Induction of the tolerant state in the absence of specific suppressor T cells, J. Immunol., 128, 2378, 1982.
94. Mowat, A. McI., Strobel, S., Drummond, H. E., and Ferguson, A., Immunological responses to fed protein antigens in mice. I. Reversal of oral tolerance to ovalbumin by cyclophosphamide, Immunology, 45, 104, 1982.
95. Whitacre, C. C., Gienapp, I. E., Orosz, C. G., and Bitar, D. M., Oral tolerance in experimental autoimmune encephalomyelitis. III. Evidence for clonal anergy, J. Immunol., 147, 2155, 1991.
96. Melamed, D. and Friedman, A., Direct evidence for anergy in T lymphocytes tolerized by oral administration of ovalbumin, Eur. J. Immunol., 23, 935, 1993.
97. h1 lymphocytes following a single feed with ovalbumin: anergy in the absence of suppression, Eur. J. Immunol., 24, 1974, 1994.
98. Schwartz, R. H., Acquisition of self-tolerance, Cell, 57, 1073, 1989.
99. Kearney, E. R., Pape, K. A., Loh, D. Y., and Jenkins, M. K., Visualization of peptide-specific T cell immunity and peripheral tolerance induction in vivo, Immunity, 1, 327, 1994.
100. Lo, D., Burkly, L. C., Flavell, R. A., Palmiter, R. D., and Brinster, R. L., Tolerance in transgenic mice expressing class II major histocompatibility complex on pancreatic acinar cells, J. Exp. Med., 170, 87, 1989.
101. Scott, B., Kaye, J., Lo, D., Lechler, R., and Lombardi, G., T cells and suppression in vitro, Science, 266, 464, 1994.
102. Mueller, D. L. and Jenkins, M. K., Molecular mechanisms underlying functional T-cell unresponsiveness, Curr. Opin. Immunol., 7, 375, 1995.
103. Strobel, S., Mowat, A. McI., and Ferguson, A., Prevention of oral tolerance induction to ovalbumin and enhanced antigen presentation during a graft-vs.-host reaction in mice, Immunology, 56, 57, 1985.
104. Hamann, A., Andrew, D. P., JablonskiWestrich, D., Holzmann, B., and Butcher, E. C., Role of alpha4-integrins in lymphocyte homing to mucosal tissues in vivo, J. Immunol., 152, 3282, 1994.
105. Williams, N. A., Cochrane, L., and Harper, H. M., The characteristics of local antigen-presenting cells determine the outcome of peripheral immune responses, 9th International Congress of Immunology, 1995, Abstr. 384.
106. Bland, P. W. and Warren, L. G., Antigen presentation by epithelial cells of the rat small intestine. II. Selective induction of suppressor T cells, Immunology, 9, 1986.
107. Barrett, T. A., Lee, H. O., and Hurst, S. D., Oral antigen induces trafficking of activated T cells to mucosal tissues, Abstract, Oral Tolerance: Mechanisms and Applications, Conference, The New York Academy of Sciences, 1995.
108. Meyer, A., Gienapp, I., Cox, K., Goverman, J., Hood, L., and Whitacre, C., Oral tolerance in myelin basic protein TCR transgenic mice, 9th International Congress on Immunology, 1995, Abstr. number 3598.
109. Liu, L. M. and Macpherson, G. G., Antigen acquisition by dendritic cells: intestinal dendritic cells acquire antigen administered orally and can prime naive T cells in vivo, J. Exp. Med., 177, 1299, 1993.
110. Bruce, M. G. and Ferguson, A., The influence of intestinal processing on the immunogenicity and molecular size of absorbed circulating ovalbumin in mice, Immunology, 59, 295, 1986.
111. Bruce, M. G. and Ferguson, A., Oral tolerance to ovalbumin in mice: studies of chemically modified and of "biologically filtered" antigen, Immunology, 57, 627, 1986.
112. Gahring, L. C. and Weigle, W. D., The induction of peripheral T cell unresponsiveness in adult mice by monomeric human gamma-globulin, J. Immunol., 143, 2094, 1989.
113. Sun, J. B., Holmgren, J., and Czerkinsky, C., Cholera toxin B subunit: an efficient transmucosal carrier-delivery system for induction of peripheral immunological tolerance, Proc. Natl. Acad. Sci. U.S.A., 10795, 1994.
114. Furrie, E., Turner, M. W., and Strobel, S., A functioning gut associated lymphoid system is necessary for the induction of oral tolerance: Scid mice fail to generate an oral tolerogen after enteral administration of ovalbumin, Immunology, 83, 562, 1994.
115. Bruce, M. G., Strobel, S., Hanson, D. G., and Ferguson, A., Transferable tolerance for cell-mediated immunity after feeding is prevented by radiation damage and restored by immune reconstitution, Clin. Exp. Immunol., 70, 611, 1987.
116. Furrie, E., Turner, M. W., and Strobel, S., Partial characterization of a circulating tolerogenic moiety which, after a feed of ovalbumin, suppresses delayed-type hypersensitivity in recipient mice, Immunology, 86, 480, 1995.
117. Peng, H-J., Turner, M. W., and Strobel, S., The generation of a tolerogen after a feed of ovalbumin is time dependent and unrelated to the serum level of immunoreactive protein, Clin. Exp. Immunol., 81, 510, 1990.
118. Strobel, S., Regulation of Intestinal Cell-Mediated Immunity, Ph.D. thesis, University of Edinburgh, 1984.
119. Higgins, P. J. and Weiner, H. L., Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein and its fragments, J. Immunol., 140, 440, 1988.
120. Qian, J-H., Hashimoto, T., Fujiwara, H., and Hamaoka, T., Studies on the induction of tolerance to alloantigens. I. The abrogation of potentials for delayed-type hypersensitivity responses to alloantigens by portal venous inoculation with allogeneic cells, J. Immunol., 134, 3656, 1985.
121. Thomas, H. C., Ryan, C. J., Benjamin, I. S., Blumgart, L. H., and MacSween, R. N. M., The immune response in cirrhotic rats: the induction of tolerance to orally administered protein antigens, Gastroenterology, 71, 114, 1976.
122. Yang, R., Liu, Q., Grosfeld, J. L., and Pescovitz, M. D., Intestinal venous drainage through the liver is a prerequisite for oral tolerance induction, J. Pediatr. Surg., 29, 1145, 1994.
123. Cantor, H. E. and Dumont, A. E., Hepatic suppression of sensitization to antigen absorbed into the portal system, Nature, 215, 744, 1967.
124. Mueller, D. L., Jenkins, M. K., and Schwartz, R. H., Clonal expansion vs. functional clonal inactivation, Ann. Rev. Immunol., 7, 445, 1989.
125. Geurder, S., Meyrhoff, J., and Flavell, R., The role of the T cell costimulator B7-1 in autoimmunity and the induction and maintenance of tolerance to peripheral antigen, Immunity, 1, 155, 1994.
126. Hoyne, G. F. and Thomas, W. R., T-cell responses to orally administered antigens. Study of the kinetics of lymphocyte production after single and multiple feeding, Immunology, 84, 304, 1995.
127. + T cells, J. Exp. Med., 182, 1591, 1995.
128. + T helper cell phenotype development in a T cell receptor-ab-transgenic model, J. Exp. Med., 182, 1579, 1995.
129. Matzinger, P., Tolerance, danger, and the extended family, Annu. Rev. Immunol., 991, 1994.
130. Aichele, P., Kyburz, D., Ohashi, P. S., Odermatt, B., Zinkernagel, R. M., Hengartner, H., and Pircher, H., Peptide-induced T-cell tolerance to prevent autoimmune disease in a transgenic mouse model, Proc. Natl. Acad. Sci. U.S.A., 91, 444, 1994.