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• W2006092880 abstract "Background. Intravenous immunoglobulins (IVIg) therapy is effective as a treatment for T-cell-mediated immune diseases, but whether and how IVIg suppress allogeneic T-cell responses is largely unknown. Methods. In vitro, human CD4+, CD4+CD25−, or CD4+CD25+ T cells were stimulated with allogeneic antigen-presenting cells (APCs), and mouse CBA/Ca (H2k) CD4+ or CD4+CD25− T cells were stimulated with C57BL/10 (H2b) splenocytes, in the presence or absence of IVIg. Proliferation, binding of IVIg, expression of activation markers, and ZAP70-phosphorylation were determined. In vivo, 1×105 CD4+ or CD4+CD25− T cells of CBA/Ca mice were adoptively transferred into CBA/RAG1−/− mice, which were 1 day later transplanted with skin grafts of C57BL/10 mice. IVIg was administered intravenously and skin graft survival was determined. Results. IVIg bound to the surface of human and mouse CD4+Foxp3+ regulatory T cells (Tregs). IVIg binding resulted in functional activation of Tregs, as detected by increased expression of surface activation markers, enhanced ZAP70-phosphorylation, and increased capacity to suppress allogeneic T-cell proliferation. IVIg inhibited allogeneic T-cell proliferation in the presence of Tregs, but this effect was abrogated on selective depletion of CD25+ cells from responder T cells. IVIg prevented T-cell-mediated rejection of fully mismatched skin grafts in CBA/RAG1−/− mice reconstituted with CD4+ T cells, but this effect was lost on selective depletion of CD4+CD25+ cells from transferred T cells, indicating that IVIg induced dominant allograft protection mediated by Tregs. Conclusions. Our data show that IVIg suppress allogeneic T-cell responses by direct activation of Tregs. IVIg treatment, which has been proven safe, may have therapeutic potential in tolerance-inducing strategies in transplant medicine." @default.
• W2006092880 created "2016-06-24" @default.
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• W2006092880 date "2010-06-27" @default.
• W2006092880 modified "2023-09-23" @default.
• W2006092880 title "Intravenous Immunoglobulins Promote Skin Allograft Acceptance by Triggering Functional Activation of CD4+Foxp3+ T cells" @default.
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• W2006092880 doi "https://doi.org/10.1097/tp.0b013e3181dd6bf1" @default.
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