Differential response of murine CD4+CD25+ and CD4+CD25– T cells to dexamethasone‐induced cell death

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Abstract
To evaluate the in vivo effect of immunosuppressive glucocorticoids on CD4+CD25+ T regulatory cells, we injected dexamethasone (Dex) into BALB/c mice. Administrationof Dex enhanced the proportion of CD4+CD25+ cells and the ratio of CD4+CD25+ cells to CD4+CD25– cells in the lymphoid organs, especially in thethymus. This correlates with our in vitro observation that CD4+CD25+ T cells express higher levels of glucocorticoid receptor and Bcl-2, and are therefore more resistant to Dex-mediated cell death than CD4+CD25– T cells. Furthermore, IL-2 selectively protected CD4+CD25+ T cells from Dex-induced cell death, while IL-7 and IL-15 didnot exert preferential protective effects. Dex-treated CD4+CD25+ T cells expressed higher levels of intracellular CTLA-4 and surface glucocorticoid-induced TNF receptor than fresh CD4+CD25+ T cells, but still failed to respond to TCR stimulation and inhibited proliferation of CD4+CD25– T cells. These results suggest that, in addition to suppressing cytokine transcription, Dex treatment is permissive for the survival of functional CD4+CD25+ T regulatory cells, and this property may contribute to the anti-inflammatory and immunosuppressive efficacy of glucocorticoids. Our data also suggest that selective protection of CD4+CD25+ T cell from apoptosis may constitute a role in immune tolerance for IL-2.