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IL‐2 is crucial for the production of CD4⁺CD25⁺ T regulatory (Treg) cells while important for the generation of effective T cell‐mediated immunity. How to exploit the capacity of IL‐2 to expand Treg cells, while restraining activation of T effector (Teff) cells, is an important and unanswered therapeutic question. Dexamethasone (Dex), a synthetic glucocorticoid steroid, has been reported to suppress IL‐2‐mediated activation of Teff cells and increase the proportion of Treg cells. Thus, we hypothesized that glucocorticoids may be useful as costimulants to amplify IL‐2‐mediated selective expansion of Treg cells. We show in this study that short‐term simultaneous administration of Dex and IL‐2 markedly expanded functional suppressive Foxp3⁺CD4⁺CD25⁺ T cells in murine peripheral lymphoid tissues. In a myelin oligodendrocyte glycoprotein‐induced experimental autoimmune encephalomyelitis (EAE) mouse model …