Abstract

The T‐box transcription factor expressed in T cells (T‐bet) is a critical regulator of T cell effector functions, particularly interferon gamma (IFN‐γ) production. We investigated the role of T‐bet in immunity to T. cruzi, an intracellular pathogen that causes Chagas disease in humans, and which requires both CD4+ and CD8+ T cells for successful control of the parasite. T‐bet‐deficient mice (T‐bet KO) infected with T. cruzi exhibited elevated blood parasitemia, progressive weight loss, and significant mortality. Infection was accompanied by an increase in tissue parasitism, as well as liver inflammation in T‐bet KO mice. FACS analysis revealed that CD4+ and CD8+ T cell differentiation were altered in spleens of T‐bet KO mice. In addition, there was a significant delay in the kinetics and magnitude of CD8+ T cell expansion in the blood of T‐bet KO mice. Despite an increase in T cell‐derived IL‐4 production, T cells from infected T‐bet KO mice still produced significant quantities of IFN‐γ, and serum IFN‐γ levels were elevated in T‐bet KO mice. These data demonstrate that T‐bet is required for immunity to T. cruzi, and suggests that mechanisms other than a Th1 to Th2 switch may be responsible for the increased susceptibility of T‐bet KO mice to T. cruzi infection.

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