Oral Tolerance: Physiologic Basis and Clinical Applications

Mowat, Allan McI; Faria, Ana Maria Caetano; Weiner, Howard L.

doi:10.1016/b978-012491543-5/50031-0

Cited by 35 publications

(57 citation statements)

References 472 publications

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“…O ral administration of Ag can induce peripheral, so-called oral tolerance, characterized by a decreased ability to respond immunologically to systemic immunization with the same Ag (1,2). Although when using excessive Ag doses oral tolerance may result from induction of anergy and even clonal deletion of T cells (3), under more physiological conditions oral tolerance is largely mediated through the mucosal induction of regulatory CD4 ϩ T cells producing immunomodulatory cytokines such as IL-10 and TGF-␤ that can suppress the systemic response to the same Ag.…”

mentioning

confidence: 99%

“…Despite many attractive features of oral tolerance induction as a means of potential Ag-specific immunotherapy in autoimmune and allergic disorders, it appears clear that to achieve this goal there is a need for development of Ag formulations and administration regimens with improved tolerance-inducing potency (1,2). In earlier studies, we and others have shown (17) that even microgram amounts of relevant Ag conjugated to the nontoxic protein of cholera toxin (CT) B subunit (CTB) can induce oral tolerance with unique efficacy and in an Ag-specific manner, in experimental models, suppress development of autoimmune diseases (18 -21).…”

mentioning

confidence: 99%

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Oral Tolerance Induction with Antigen Conjugated to Cholera Toxin B Subunit Generates Both Foxp3+CD25+ and Foxp3−CD25− CD4+ Regulatory T Cells

Sun

Raghavan

Sjöling

et al. 2006

The Journal of Immunology

103

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Oral administration of Ag coupled to cholera toxin B subunit (CTB) efficiently induces peripheral immunological tolerance. We investigated the extent to which this oral tolerance is mediated by CD25+CD4+ regulatory T cells (Treg). We found that total Treg, KJ1–26+ Treg and CTLA-4+ Treg were all increased in Peyer’s patches, mesenteric lymph nodes, and, to a lesser extent, in spleen of mice after intragastric administration of OVA/CTB conjugate, which also increased TGF-β in serum. This could be abolished by coadministering cholera toxin or by treatment with anti-TGF-β mAb. CD25+ Treg, but also CD25−CD4+ T cells from OVA/CTB-treated BALB/c or DO11.10 mice efficiently suppressed effector T cell proliferation and IL-2 production in vitro. Following adoptive transfer, both T cell populations also suppressed OVA-specific T cell and delayed-type hypersensitivity responses in vivo. Foxp3 was strongly expressed by CD25+ Treg from OVA/CTB-treated mice, and treatment also markedly expanded CD25+Foxp3+ Treg. Furthermore, in Rag1−/− mice that had adoptively received highly purified Foxp3−CD25−CD4+ OT-II T cells OVA/CTB feeding efficiently induced CD25+ Treg cells, which expressed Foxp3 more strongly than naturally developing Treg and also had stronger ability to suppress effector OT-II T cell proliferation. A remaining CD25− T cell population, which also became suppressive in response to OVA/CTB treatment, did not express Foxp3. Our results demonstrate that oral tolerance induced by CTB-conjugated Ag is associated with increase in TGF-β and in both the frequency and suppressive capacity of Foxp3+ and CTLA-4+ CD25+ Treg together with the generation of both Foxp3+ and Foxp3−CD25− CD4+ Treg.

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mentioning

confidence: 99%

mentioning

confidence: 99%

Oral Tolerance Induction with Antigen Conjugated to Cholera Toxin B Subunit Generates Both Foxp3+CD25+ and Foxp3−CD25− CD4+ Regulatory T Cells

Sun

Raghavan

Sjöling

et al. 2006

The Journal of Immunology

103

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“…Iriani T. Tobagus, Wayne R. Thomas, and Patrick G. Holt 1 In this report we demonstrate that although passive feeding of specific Ag to mice as neonates or adults can induce oral tolerance in both the cellular and humoral arms of the immune response, quantitative and, in particular, qualitative aspects of the tolerance process are determined by the nature of the inflammatory costimuli provided at the time of secondary Ag challenge. Moreover, this dependency upon nonspecific costimulation is more profound in Ag-fed neonates than in their adult counterparts.…”

Section: Adjuvant Costimulation During Secondary Antigen Challenge DImentioning

confidence: 93%

“…This form of tolerance can be induced to a wide range of Ags, and a number of host factors, such as age, genetic background, and nutritional status, influence the induction and maintenance of oral tolerance (reviewed in Ref. 1). Of particular interest to this report, oral tolerance has been found to be defective in early infancy in a number of experimental animal models (2)(3)(4)(5).…”

Section: Adjuvant Costimulation During Secondary Antigen Challenge DImentioning

confidence: 99%

“…O ral tolerance is considered an important physiological mechanism that protects against hypersensitivity to food Ags and Ags from the microflora of the gastrointestinal tract (reviewed in Ref. 1). This form of tolerance can be induced to a wide range of Ags, and a number of host factors, such as age, genetic background, and nutritional status, influence the induction and maintenance of oral tolerance (reviewed in Ref.…”

Section: Adjuvant Costimulation During Secondary Antigen Challenge DImentioning

confidence: 99%

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Adjuvant Costimulation during Secondary Antigen Challenge Directs Qualitative Aspects of Oral Tolerance Induction, Particularly during the Neonatal Period

Tobagus

Thomas

Holt

2004

The Journal of Immunology

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In this report we demonstrate that although passive feeding of specific Ag to mice as neonates or adults can induce oral tolerance in both the cellular and humoral arms of the immune response, quantitative and, in particular, qualitative aspects of the tolerance process are determined by the nature of the inflammatory costimuli provided at the time of secondary Ag challenge. Moreover, this dependency upon nonspecific costimulation is more profound in Ag-fed neonates than in their adult counterparts. Thus, administration of Ag in the Th1-selective adjuvant CFA to prefed animals resulted in significant inhibition of IgG2a, IL-2, and IFN-γ responses, whereas IL-5 responses were increased. In contrast, rechallenge with Ag in the Th2-selective adjuvant aluminum hydroxide resulted in significant inhibition of IgG1, IgE, IL-2, and IL-5 responses, whereas IFN-γ responses were increased. Additionally, although soluble Ag challenge of prefed adults revealed marginal tolerogenic effects, the same challenge protocol in animals prefed as neonates elicited enhanced Th2-dependent IgG1 production. These results suggest that inflammatory stimulation at the time of Ag challenge is obligatory to trigger oral tolerance mechanisms, particularly in animals fed as neonates and also that the type of adjuvant used at the time of challenge selects for the type of Th cell population to be inhibited.

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Efficacy of an inactivated recombinant vaccine encoding a fimbrial protein of Pasteurella multocida B:2 against hemorrhagic septicemia in goats

Yasin

Yusoff

Zamri-Saad

et al. 2010

Trop Anim Health Prod

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This study was carried out to determine the antibody responses and protective capacity of an inactivated recombinant vaccine expressing the fimbrial protein of Pasteurella multocida B:2 following intranasal vaccination against hemorrhagic septicemia in goats. Goats were vaccinated intranasal with 10(6) CFU/mL of the recombinant vaccine (vaccinated group) and 10(6) CFU/mL of pET32/LIC vector without fimbrial protein (control group). All three groups were kept separated before all goats in the three groups were challenged with 10(9) CFU/mL of live pathogenic P. multocida B:2. During the course of study, both serum and lung lavage fluid were collected to evaluate the antibody levels via enzyme-linked immunosorbent assay. It was found that goats immunized with the inactivated recombinant vaccine developed a strong and significantly (p < 0.05) higher specific IgA and IgG responses in both serum and lung lavage fluid samples compared to the control and unvaccinated groups. Following intratracheal challenge, the rate of isolation was 17% for the vaccinated group, 67% for the control group and 100% for the unvaccinated group. However, none of the goat from the vaccinated group had P. multocida B:2 in the liver, tonsil and heart. Therefore, the study revealed that an inactivated recombinant vaccine significantly provides significant protection against high dose challenge and enhances the stimulation of the local and systemic immunities.

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Oral Tolerance: Physiologic Basis and Clinical Applications

Cited by 35 publications

References 472 publications

Oral Tolerance Induction with Antigen Conjugated to Cholera Toxin B Subunit Generates Both Foxp3+CD25+ and Foxp3−CD25− CD4+ Regulatory T Cells

Oral Tolerance Induction with Antigen Conjugated to Cholera Toxin B Subunit Generates Both Foxp3+CD25+ and Foxp3−CD25− CD4+ Regulatory T Cells

Adjuvant Costimulation during Secondary Antigen Challenge Directs Qualitative Aspects of Oral Tolerance Induction, Particularly during the Neonatal Period

Efficacy of an inactivated recombinant vaccine encoding a fimbrial protein of Pasteurella multocida B:2 against hemorrhagic septicemia in goats

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