Synthetic glucocorticoids (GCs) are commonly used in the treatment of inflammatory diseases, but the role of endogenous GCs in the regulation of host-protective immune responses is poorly understood. Here we show that GCs are induced during acute Toxoplasma gondii infection and directly control the T cell response to the parasite. When infected with toxoplasma, mice that selectively lack GC receptor (GR) expression in T cells (GR^lck-Cre) rapidly succumb to infection despite displaying parasite burdens indistinguishable from control animals and unaltered levels of the innate cytokines IL-12 and IL-27. Mortality in the GR^lck-Cre mice was associated with immunopathology and hyperactive Th1 cell function as revealed by enhanced IFN-γ and TNF production in vivo. Unexpectedly, these CD4⁺ T lymphocytes also overexpressed IL-10. Importantly, CD4⁺ T cell depletion in wild-type or GR^lck-Cre mice led to ablation of the GC response to infection. Moreover, in toxoplasma-infected RAG^−/− animals, adoptive transfer of CD4⁺ T lymphocytes was required for GC induction. These findings establish a novel IL-10–independent immunomodulatory circuit in which CD4⁺ T cells trigger a GC response that in turn dampens their own effector function. In the case of T. gondii infection, this self-regulatory pathway is critical for preventing collateral tissue damage and promoting host survival.