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Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll-like receptors


Meiler, F; Klunker, S; Zimmermann, M; Akdis, C A; Akdis, M (2009). Distinct regulation of IgE, IgG4 and IgA by T regulatory cells and toll-like receptors. Allergy, 63(11):1455-1463.

Abstract

BACKGROUND: Allergic diseases are characterized by the activation of the immune system and formation of immunoglobulin (Ig)E antibodies against normally innocuous environmental antigens, whereas IgG4 and IgA represent noninflammatory and blocking antibody isotypes. The T helper 2 (Th2) cells induce and T regulatory (Treg) cells suppress several features of allergic inflammation. Our aim was to investigate the role of allergen-specific T regulatory type 1 (Tr1) cells and CD4(+)CD25(+) Treg cells and toll-like receptors (TLRs) on IgE, IgG4 and IgA production. METHODS: Germline or productive Ig-transcripts are determined by real-time reverse transcriptase-polymerase chain reaction, secreted Igs are measured by enzyme-linked immunosorbent assay and the frequency of Ig-producing plasma cells is investigated by enzyme-linked immunosorbent spot. Circulating CD4(+)CD25(+) Treg cells and allergen-specific Tr1 cells are used. RESULTS: Both allergen-specific, interleukin-10-secreting Tr1 cells and CD4(+)CD25(+) Treg cells from healthy individuals induced IgG4 and suppressed IgE production in peripheral blood mononuclear cells and purified B-cell cultures. In contrast, induction of IgA production is independent of T-cell help and the role of Tr1 or Treg cells is very limited, whereas it was highly induced by direct B-cell activation via TLR7 and 9. CONCLUSIONS: These data suggest that T regulatory cells may contribute to the suppression of allergic diseases by suppression of IgE and induction of IgG4, whereas IgA production is enhanced by B-cell activation via TLR7 and TLR9.

Abstract

BACKGROUND: Allergic diseases are characterized by the activation of the immune system and formation of immunoglobulin (Ig)E antibodies against normally innocuous environmental antigens, whereas IgG4 and IgA represent noninflammatory and blocking antibody isotypes. The T helper 2 (Th2) cells induce and T regulatory (Treg) cells suppress several features of allergic inflammation. Our aim was to investigate the role of allergen-specific T regulatory type 1 (Tr1) cells and CD4(+)CD25(+) Treg cells and toll-like receptors (TLRs) on IgE, IgG4 and IgA production. METHODS: Germline or productive Ig-transcripts are determined by real-time reverse transcriptase-polymerase chain reaction, secreted Igs are measured by enzyme-linked immunosorbent assay and the frequency of Ig-producing plasma cells is investigated by enzyme-linked immunosorbent spot. Circulating CD4(+)CD25(+) Treg cells and allergen-specific Tr1 cells are used. RESULTS: Both allergen-specific, interleukin-10-secreting Tr1 cells and CD4(+)CD25(+) Treg cells from healthy individuals induced IgG4 and suppressed IgE production in peripheral blood mononuclear cells and purified B-cell cultures. In contrast, induction of IgA production is independent of T-cell help and the role of Tr1 or Treg cells is very limited, whereas it was highly induced by direct B-cell activation via TLR7 and 9. CONCLUSIONS: These data suggest that T regulatory cells may contribute to the suppression of allergic diseases by suppression of IgE and induction of IgG4, whereas IgA production is enhanced by B-cell activation via TLR7 and TLR9.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Swiss Institute of Allergy and Asthma Research
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:March 2009
Deposited On:12 Mar 2009 16:47
Last Modified:05 Apr 2016 13:04
Publisher:Wiley-Blackwell
ISSN:0105-4538
Publisher DOI:https://doi.org/10.1111/j.1398-9995.2008.01774.x
PubMed ID:18925882

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