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Lack of local suppression in orally tolerant CD8-deficient mice reveals a critical regulatory role of CD8+ T cells in the normal gut mucosa.

Journal article
Authors Dubravka Grdic Eliasson
Elisabeth Hultgren-Hörnquist
Martin Kjerrulf
Nils Y Lycke
Published in Journal of immunology (Baltimore, Md. : 1950)
Volume 160
Issue 2
Pages 754-62
ISSN 0022-1767
Publication year 1998
Published at Institute of Laboratory Medicine, Dept of Clinical Immunology
Institute of Medical Microbiology/Immunology
Pages 754-62
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Adjuvants, Immunologic, administration & dosage, Animals, Antigens, administration & dosage, Antigens, CD8, genetics, CD8-Positive T-Lymphocytes, immunology, Cholera Toxin, administration & dosage, Eating, genetics, immunology, Hemocyanin, administration & dosage, immunology, Immune Tolerance, genetics, immunology, Intestinal Mucosa, cytology, immunology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Th1 Cells, immunology, Th2 Cells, immunology
Subject categories Biological Sciences, Basic Medicine

Abstract

We found that feeding keyhole limpet hemocyanin (KLH) to CD8-deficient (CD8-/-) mice induced oral tolerance that was comparable in both magnitude and quality to that induced in wild-type (wt) mice. The tolerance was dose dependent, and only higher doses of KLH caused significant reduction in specific Ab and T cell responses. Both Th1 and Th2 CD4+ T cell functions were affected. Feeding KLH together with cholera toxin (CT) adjuvant, however, abrogated the induction of oral tolerance equally well in CD8-/- and wt mice. On the contrary, CT adjuvant was unable to abrogate already established oral tolerance in both CD8-/- and wt mice. Most importantly, whereas Ag feeding induced hyporesponsiveness in systemic as well as in local gut IgA responses in wt mice, a lack of local suppression was evident in orally tolerant CD8-/- mice following oral immunizations. Thus, contrary to the situation in wt mice, Ag feeding induces systemic, but not local, gut IgA hyporesponsiveness in CD8-/- mice, suggesting that CD8+ T cells in the normal gut mucosa exert an important down-regulatory function. In wt mice the local suppression extended to an unrelated Ag, OVA, given together with KLH and CT adjuvant, i.e., bystander suppression. Based on these results we propose that tolerance induced by feeding Ag is highly compartmentalized, requiring CD8+ T cells for local suppression of IgA responses, whereas systemic tolerance may affect CD4+ T cells of both Th1 and Th2 types independently of CD8+ T cells. Finally, the adjuvant effect of CT abrogates induction, but not established, oral tolerance through a mechanism that does not require CD8+ T cells.

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