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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

Gribonika, Inta LU orcid ; Eliasson, Dubravka Grdic ; Chandode, Rakesh K ; Schön, Karin ; Strömberg, Anneli ; Bemark, Mats LU orcid and Lycke, Nils Y (2019) In Mucosal Immunology 12(6). p.1268-1279
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... (More)

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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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adjuvants, Immunologic/administration & dosage, Adoptive Transfer, Animals, B-Lymphocytes/drug effects, Cells, Cultured, Cholera Toxin/administration & dosage, Coculture Techniques, DNA-Binding Proteins/immunology, Immunization, Immunoglobulin A/genetics, Immunoglobulin Class Switching/drug effects, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Nude, Mice, SCID, Mice, Transgenic, Neuropilin-1/immunology, Ovalbumin/administration & dosage, Peyer's Patches/immunology, T-Lymphocytes, Helper-Inducer/drug effects, T-Lymphocytes, Regulatory/drug effects, Thymus Gland/drug effects, Transcription Factors/immunology
in
Mucosal Immunology
volume
12
issue
6
pages
1268 - 1279
publisher
Elsevier
external identifiers
  • pmid:31501516
  • scopus:85072044322
ISSN
1933-0219
DOI
10.1038/s41385-019-0202-0
language
English
LU publication?
no
id
ea026a64-27b4-49c0-abf0-cc12d29afa8c
date added to LUP
2023-12-06 16:44:45
date last changed
2026-01-12 20:57:44
@article{ea026a64-27b4-49c0-abf0-cc12d29afa8c,
  abstract     = {{<p>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.</p>}},
  author       = {{Gribonika, Inta and Eliasson, Dubravka Grdic and Chandode, Rakesh K and Schön, Karin and Strömberg, Anneli and Bemark, Mats and Lycke, Nils Y}},
  issn         = {{1933-0219}},
  keywords     = {{Adjuvants, Immunologic/administration & dosage; Adoptive Transfer; Animals; B-Lymphocytes/drug effects; Cells, Cultured; Cholera Toxin/administration & dosage; Coculture Techniques; DNA-Binding Proteins/immunology; Immunization; Immunoglobulin A/genetics; Immunoglobulin Class Switching/drug effects; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Mice, SCID; Mice, Transgenic; Neuropilin-1/immunology; Ovalbumin/administration & dosage; Peyer's Patches/immunology; T-Lymphocytes, Helper-Inducer/drug effects; T-Lymphocytes, Regulatory/drug effects; Thymus Gland/drug effects; Transcription Factors/immunology}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1268--1279}},
  publisher    = {{Elsevier}},
  series       = {{Mucosal Immunology}},
  title        = {{Class-switch recombination to IgA in the Peyer's patches requires natural thymus-derived Tregs and appears to be antigen independent}},
  url          = {{http://dx.doi.org/10.1038/s41385-019-0202-0}},
  doi          = {{10.1038/s41385-019-0202-0}},
  volume       = {{12}},
  year         = {{2019}},
}