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

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.