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KMID : 0381120120340060619
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Genes and Genomics
2012 Volume.34 No. 6 p.619 ~ p.625
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TGF-β and BAFF derived from CD4+CD25+Foxp3+ T cells mediate mouse IgA isotype switching
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Park Kyoung-Hoon
Seo Goo-Young
Jang Young-Saeng
Kim Pyeung-Hyeun
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Abstract
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TGF-β1 is generally accepted as the physiological IgA isotype switch factor. Nevertheless, it is unclear as to which cells in mucus-associated lymphoid tissue provide this cytokine to B cells. Regulatory T cells (Tregs) play immune-suppressive roles by secreting inhibitory cytokines such as TGF-β and IL-10. Thus, it is plausible that Tregs are involved in IgA class switch recombination (CSR) in MALT. We explored, in the present study, the possibility that CD4+CD25+ T cells facilitate IgA CSR in murine B cells. In cocultures, CD4+CD25+Foxp3+ T cells stimulated IgA production by splenic B cells to a greater extent than did CD4+CD25?Foxp3? T cells. This effect was markedly abrogated by the addition of anti-TGF-β1 Ab. Additionally, IgA production was paralleled by an increase in germ line transcript α (GLTα), an indicator of IgA CSR. In contrast, CD4+CD25?Foxp3? T cells were more potent at inducing GLTγ1 and GLT? production by cocultured splenic B cells than were CD4+CD25+Foxp3+ T cells. Consistent with these results, phenotypic analyses revealed that TGF-β1 and IL-4 were predominantly expressed by CD4+CD25+Foxp3+ T cells and CD4+CD25?Foxp3? T cells, respectively. Furthermore, CD4+CD25+ T cells strongly expressed BAFF, which led to activation-induced deaminase (AID) expression in B cells. Taken together, our results suggest that CD4+CD25+ Tregs have an important effect on IgA isotype commitment by expressing TGF-β1 and BAFF in MALT.
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KEYWORD
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AID, BAFF, IgA, Ig class switch recombination, Regulatory T cells, TGF-β1
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