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The influence of costimulation and regulatory CD4+ T cells on intestinal IgA immune responses.

Journal article
Authors Eva Gärdby
D Kagrdic
Martin Kjerrulf
A Bromander
M Vajdy
Elisabeth Hultgren-Hörnquist
Nils Y Lycke
Published in Developmental immunology
Volume 6
Issue 1-2
Pages 53-60
ISSN 1044-6672
Publication year 1998
Published at Institute of Laboratory Medicine, Dept of Clinical Immunology
Institute of Medical Microbiology/Immunology
Pages 53-60
Language en
Links www.ncbi.nlm.nih.gov/entrez/query.f...
Keywords Animals, Antigens, CD, Antigens, Differentiation, physiology, B-Lymphocytes, physiology, CD4-Positive T-Lymphocytes, physiology, CD40 Ligand, CTLA-4 Antigen, Cell Differentiation, Germinal Center, physiology, Immunoconjugates, Immunoglobulin A, biosynthesis, Interleukin-4, genetics, physiology, Interleukin-6, genetics, physiology, Intestinal Mucosa, immunology, Membrane Glycoproteins, physiology, Mice, Mice, Knockout
Subject categories Biological Sciences, Basic Medicine

Abstract

It is thought that IgA B-cell differentiation is highly dependent on activated CD4+ T cells. In particular, cell-cell interactions in the Peyer's patches involving CD40 and/or CD80/CD86 have been implicated in germinal-center formation and IgA B-cell development. Also soluble factors, such as IL-4, IL-5, IL-6, and TGF beta may be critical for IgA B-cell differentiation in vivo. Here we report on some paradoxical findings with regard to IgA B-cell differentiation and specific mucosal immune responses that we have recently made using gene knockout mice. More specifically, we have investigated to what extent absence of CD4+ T cells, relevant cytokines, or T-cell-B-cell interactions would influence IgA B-cell differentiation in vivo. Using CD4- or IL-4-gene knockout mice or mice made transgenic for CTLA4Ig, we found that, although specific responses were impaired, total IgA production and IgA B-cell differentiation appeared to proceed normally. However, a poor correlation was found between, on the one hand, GC formation and IgA differentiation and, on the other hand, the ability to respond to T-cell-dependent soluble protein antigens in these mice. Thus, despite the various deficiencies in CD4+ T-cell functions seemingly intact IgA B-cell development was observed.

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