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G protein‐coupled receptor kinase interactor 2 (GIT2) is a signaling scaffold protein involved in regulation of cytoskeletal dynamics and the internalization of G protein‐coupled receptors (GPCRs). The short‐splice form of GIT2 is expressed in peripheral T cells and thymocytes. However, the functions of GIT2 in T cells have not yet been determined. We show that treatment with Con A in a model of polyclonal T‐lymphocyte activation resulted in marked inhibitions in the intrahepatic infiltration of inflammatory cells, cytokine response and acute liver failure inGit2−/− mice. CD4+ T cells fromGit2−/− mice showed significant impairment in proliferation, cytokine production and signal transduction upon TCR‐stimulated activation. Our results suggested that GIT2 plays an important role in T‐cell functionin vivo andin vitro.