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Class-switch recombination to IgA in the Peyer's patches requires natural thymus-derived Tregs and appears to be antigen independent.

Journal article
Authors Inta Gribonika
Dubravka Grdic Eliasson
Rakesh Chandode
Karin Schön
Anneli Strömberg
Mats Bemark
Nils Y Lycke
Published in Mucosal immunology
Volume 12
Issue 6
Pages 1268-1279
ISSN 1935-3456
Publication year 2019
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Pages 1268-1279
Language en
Links dx.doi.org/10.1038/s41385-019-0202-...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Immunology, Microbiology and immunology, Immunology in the medical area

Abstract

Our understanding of how class-switch recombination (CSR) to IgA occurs in the gut is still incomplete. Earlier studies have indicated that Tregs are important for IgA CSR and these cells were thought to transform into follicular helper T cells (Tfh), responsible for germinal center formation in the Peyer's patches (PP). Following adoptive transfer of T-cell receptor-transgenic (TCR-Tg) CD4 T cells into nude mice, we unexpectedly found that oral immunization did not require an adjuvant to induce strong gut IgA and systemic IgG responses, suggesting an altered regulatory environment in the PP. After sorting of splenic TCR-Tg CD4 T cells into CD25+ or CD25- cells we observed that none of these fractions supported a gut IgA response, while IgG responses were unperturbed in mice receiving the CD25- cell fraction. Hence, while Tfh functions resided in the CD25- fraction the IgA CSR function in the PP was dependent on CD25+ Foxp3+ Tregs, which were found to be Helios+ neuropilin-1+ thymus-derived Tregs. This is the first study to demonstrate that Tfh and IgA CSR functions are indeed, unique, and separate functions in the PP with the former being TCR-dependent while the latter appeared to be antigen independent.

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