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J R Soc Med. 1995 January; 88(1): 14–17.
PMCID: PMC1295066

A review of the mechanisms of oral tolerance and immunotherapy.

Abstract

The induction of oral tolerance by oral immunization has been well recognized. Accumulated evidence shows that oral tolerance can be mediated by orally activated humoral and cellular factors. In animal models, the development of several T cell-mediated autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, uveitis and diabetes type 1 can be inhibited by oral immunization of the respective antigens. In allergy, oral administration of certain allergens can prevent and reduce both contact and atopic dermatitis. Oral tolerance to alloantigen also reduces graft rejection. In spite of these encouraging results, the usefulness of this approach for an alternative immunotherapy in humans needs to be investigated further.

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Selected References

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  • André C, Heremans JF, Vaerman JP, Cambiaso CL. A mechanism for the induction of immunological tolerance by antigen feeding: antigen-antibody complexes. J Exp Med. 1975 Dec 1;142(6):1509–1519. [PMC free article] [PubMed]
  • Hanson DG, Vaz NM, Maia LC, Lynch JM. Inhibition of specific immune responses by feeding protein antigens. III. Evidence against maintenance of tolerance to ovalbumin by orally induced antibodies. J Immunol. 1979 Nov;123(5):2337–2343. [PubMed]
  • Kagnoff MF. Effects of antigen-feeding on intestinal and systemic immune responses. III. Antigen-specific serum-mediated suppression of humoral antibody responses after antigen feeding. Cell Immunol. 1978 Sep 15;40(1):186–203. [PubMed]
  • Jackson S, Mestecky J. Oral-parenteral immunization leads to the appearance of IgG auto-anti-idiotypic cells in mucosal tissues. Cell Immunol. 1981 May 15;60(2):498–502. [PubMed]
  • Bhogal BS, Karkhanis YD, Bell MK, Sanchez P, Zemcik B, Siskind GW, Thorbecke GJ. Production of auto-anti-idiotypic antibody during the normal immune response. XII. Enhanced auto-anti-idiotypic antibody production as a mechanism for apparent B-cell tolerance in rabbits after feeding antigen. Cell Immunol. 1986 Aug;101(1):93–104. [PubMed]
  • Mattingly JA, Waksman BH. Immunologic suppression after oral administration of antigen. II. Antigen-specific helper and suppressor factors produced by spleen cells of rats fed sheep erythrocytes. J Immunol. 1980 Sep;125(3):1044–1047. [PubMed]
  • Mattingly JA, Kaplan JM, Janeway CA., Jr Two distinct antigen-specific suppressor factors induced by the oral administration of antigen. J Exp Med. 1980 Sep 1;152(3):545–554. [PMC free article] [PubMed]
  • Richman LK, Graeff AS, Yarchoan R, Strober W. Simultaneous induction of antigen-specific IgA helper T cells and IgG suppressor T cells in the murine Peyer's patch after protein feeding. J Immunol. 1981 Jun;126(6):2079–2083. [PubMed]
  • Gautam SC, Battisto JR. Orally induced tolerance generates an efferently acting suppressor T cell and an acceptor T cell that together down-regulate contact sensitivity. J Immunol. 1985 Nov;135(5):2975–2983. [PubMed]
  • Challacombe SJ. Cellular factors in the induction of mucosal immunity by oral immunization. Adv Exp Med Biol. 1987;216B:887–899. [PubMed]
  • Gautam SC, Chikkala NF, Battisto JR. Oral administration of the contact sensitizer trinitrochlorobenzene: initial sensitization and subsequent appearance of a suppressor population. Cell Immunol. 1990 Feb;125(2):437–448. [PubMed]
  • MacDonald TT. Immunosuppression caused by antigen feeding. I. Evidence for the activation of a feedback suppressor pathway in the spleens of antigen-fed mice. Eur J Immunol. 1982 Sep;12(9):767–773. [PubMed]
  • 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 U S A. 1992 Jan 1;89(1):421–425. [PubMed]
  • Whitacre CC, Gienapp IE, Orosz CG, Bitar DM. Oral tolerance in experimental autoimmune encephalomyelitis. III. Evidence for clonal anergy. J Immunol. 1991 Oct 1;147(7):2155–2163. [PubMed]
  • Melamed D, Friedman A. Direct evidence for anergy in T lymphocytes tolerized by oral administration of ovalbumin. Eur J Immunol. 1993 Apr;23(4):935–942. [PubMed]
  • Bloom BR, Salgame P, Diamond B. Revisiting and revising suppressor T cells. Immunol Today. 1992 Apr;13(4):131–136. [PubMed]
  • Street NE, Mosmann TR. Functional diversity of T lymphocytes due to secretion of different cytokine patterns. FASEB J. 1991 Feb;5(2):171–177. [PubMed]
  • Asherson GL, Zembala M, Perera MA, Mayhew B, Thomas WR. Production of immunity and unresponsiveness in the mouse by feeding contact sensitizing agents and the role of suppressor cells in the peyer's patches, mesenteric lymph nodes and other lymphoid tissues. Cell Immunol. 1977 Sep;33(1):145–155. [PubMed]
  • Green DR, Gold J, St Martin S, Gershon R, Gershon RK. Microenvironmental immunoregulation: possible role of contrasuppressor cells in maintaining immune responses in gut-associated lymphoid tissues. Proc Natl Acad Sci U S A. 1982 Feb;79(3):889–892. [PubMed]
  • Fujihashi K, Taguchi T, McGhee JR, Eldridge JH, Bruce MG, Green DR, Singh B, Kiyono H. Regulatory function for murine intraepithelial lymphocytes. Two subsets of CD3+, T cell receptor-1+ intraepithelial lymphocyte T cells abrogate oral tolerance. J Immunol. 1990 Oct 1;145(7):2010–2019. [PubMed]
  • Suzuki I, Kitamura K, Kiyono H, Kurita T, Green DR, McGhee JR. Isotype-specific immunoregulation. Evidence for a distinct subset of T contrasuppressor cells for IgA responses in murine Peyer's patches. J Exp Med. 1986 Aug 1;164(2):501–516. [PMC free article] [PubMed]
  • Fujihashi K, Kiyono H, Aicher WK, Green DR, Singh B, Eldridge JH, McGhee JR. Immunoregulatory function of CD3+, CD4-, and CD8- T cells. Gamma delta T cell receptor-positive T cells from nude mice abrogate oral tolerance. J Immunol. 1989 Dec 1;143(11):3415–3422. [PubMed]
  • Higgins PJ, Weiner HL. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin basic protein and its fragments. J Immunol. 1988 Jan 15;140(2):440–445. [PubMed]
  • Bitar DM, Whitacre CC. Suppression of experimental autoimmune encephalomyelitis by the oral administration of myelin basic protein. Cell Immunol. 1988 Apr 1;112(2):364–370. [PubMed]
  • Weiner HL, Mackin GA, Matsui M, Orav EJ, Khoury SJ, Dawson DM, Hafler DA. Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis. Science. 1993 Feb 26;259(5099):1321–1324. [PubMed]
  • Thompson SJ, Thompson HS, Harper N, Day MJ, Coad AJ, Elson CJ, Staines NA. Prevention of pristane-induced arthritis by the oral administration of type II collagen. Immunology. 1993 May;79(1):152–157. [PubMed]
  • Nagler-Anderson C, Bober LA, Robinson ME, Siskind GW, Thorbecke GJ. Suppression of type II collagen-induced arthritis by intragastric administration of soluble type II collagen. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7443–7446. [PubMed]
  • Thompson HS, Staines NA. Could specific oral tolerance be a therapy for autoimmune disease? Immunol Today. 1990 Nov;11(11):396–399. [PubMed]
  • Caspi RR, Kuwabara T, Nussenblatt RB. Characterization of a suppressor cell line which downgrades experimental autoimmune uveoretinitis in the rat. J Immunol. 1988 Apr 15;140(8):2579–2584. [PubMed]
  • Zhang ZJ, Davidson L, Eisenbarth G, Weiner HL. Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10252–10256. [PubMed]
  • van Hoogstraten IM, Boden D, von Blomberg ME, Kraal G, Scheper RJ. Persistent immune tolerance to nickel and chromium by oral administration prior to cutaneous sensitization. J Invest Dermatol. 1992 Nov;99(5):608–616. [PubMed]
  • Van Hoogstraten IM, Andersen KE, Von Blomberg BM, Boden D, Bruynzeel DP, Burrows D, Camarasa JG, Dooms-Goossens A, Kraal G, Lahti A, et al. Reduced frequency of nickel allergy upon oral nickel contact at an early age. Clin Exp Immunol. 1991 Sep;85(3):441–445. [PubMed]
  • Santucci B, Cristaudo A, Cannistraci C, Picardo M. Nickel sensitivity: effects of prolonged oral intake of the element. Contact Dermatitis. 1988 Sep;19(3):202–205. [PubMed]
  • Björkstén B, Möller C, Broberger U, Ahlstedt S, Dreborg S, Johansson SG, Juto P, Lanner A. Clinical and immunological effects of oral immunotherapy with a standardized birch pollen extract. Allergy. 1986 May;41(4):290–295. [PubMed]
  • Ishii A, Ino Y, Haida M, Dohi M, Suko M, Morita Y, Ito K, Okudaira H. Inhibition of allergen-induced bronchoconstriction in sensitized guinea pigs by orally administered allergen. Int Arch Allergy Appl Immunol. 1991;94(1-4):288–290. [PubMed]
  • Sayegh MH, Zhang ZJ, Hancock WW, Kwok CA, Carpenter CB, Weiner HL. Down-regulation of the immune response to histocompatibility antigens and prevention of sensitization by skin allografts by orally administered alloantigen. Transplantation. 1992 Jan;53(1):163–166. [PubMed]
  • 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 U S A. 1992 Aug 15;89(16):7762–7766. [PubMed]

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