Hyperexpression of Foxp3 and IDO During Acute Rejection of Islet Allografts


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Abstract

Background.We investigated the hypothesis that Foxp3+ cells are an integral component of antiallograft immunity but are dominated by pathogenic effectors.Methods.Wild-type H-2b C57BL/6 (B6) mice or B6 mice with a targeted disruption of c-Rel gene (c-Rel−/−) were used as recipients of islet grafts from allogeneic DBA/2 (H-2d) mice or syngeneic B6 mice. We developed kinetic quantitative polymerase chain reaction assays and measured intragraft expression of mRNA for Foxp3, IDO, cytolytic molecules, proinflammatory cytokines, and chemokines/receptors.Results.Intraislet levels of mRNA for Foxp3, IDO, CD3, CD25, tumor necrosis factor-α, RANTES, IP-10, and CXCR3 were highest in DBA/2 islet allografts from WT B6 recipients compared to DBA/2 islet allografts from c-Rel−/− B6 recipients or syngeneic B6 islet grafts from WT B6 mice. The ratio of granzyme B or IFN-gamma to Foxp3 was higher with the DBA/2 islet allografts from the WT B6 recipients compared to DBA/2 islet allografts from c-Rel−/− B6 recipients or B6 islet grafts from WT B6 recipients.Conclusions.Foxp3+ cells are an integral component of acute rejection of allografts but may be dominated by pathogenic effectors.

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