Journal Article

Antigen‐specific, CD4<sup>+</sup>CD25<sup>+</sup> regulatory T cell clones induced in Peyer’s patches

Noriko M. Tsuji, Koko Mizumachi and Jun‐ichi Kurisaki

in International Immunology

Published on behalf of Japanese Society for Immunology

Volume 15, issue 4, pages 525-534
Published in print April 2003 | ISSN: 0953-8178
Published online April 2003 | e-ISSN: 1460-2377 | DOI:
Antigen‐specific, CD4+CD25+ regulatory T cell clones induced in Peyer’s patches

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Since intestine is exposed to numerous exogenous antigens such as food and commensal bacteria, the organ bears efficient mechanisms for establishment of tolerance and induction of regulatory T cells (Treg). Intestinal and inducible Treg include Tr1‐like and Th3 cells whose major effector molecules are IL‐10 and transforming growth factor (TGF)‐β. These antigen‐specific Treg are expected to become clinical targets to modify the inflammatory immune response associated with allergy, autoimmune diseases and transplantation. In the present study, we characterized the antigen‐specific Treg induced in the intestine by orally administering high‐dose β‐lactoglobulin (BLG) to BALB/c mice. Seven days after feeding, only Peyer’s patch (PP) cells among different organs exerted significant suppressive effect on antibody production upon in vitro BLG stimulation. This suppressive effect was also prominent in six BLG‐specific CD4+ T cell clones (OPP1–6) established from PP from mice orally administered with high doses of BLG and was partially reversed by antibodies to TGF‐β. Intravenous transfer of OPP2 efficiently suppressed BLG‐specific IgG1 production in serum following immunization, indicating the role of such Treg in the systemic tolerance after oral administration of antigen (oral tolerance). OPP clones secrete TGF‐β, IFN‐γ and low levels of IL‐10, a cytokine pattern similar to that secreted by anergic T cells. OPP clones bear a CD4+CD25+ phenotype and show significantly lower proliferative response compared to Th0 clones. This lower response is recovered by the addition of IL‐2. Thus, antigen‐specific CD4+CD25+ Treg, which have characteristics of anergic cells and actively suppress antibody production are induced in PP upon oral administration of protein antigen.

Keywords: active suppression, oral tolerance

Journal Article.  7502 words.  Illustrated.

Subjects: Immunology ; Biological Sciences

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