Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion

Significance During a chronic viral infection, prolonged exposure to viral antigens leads to dysfunction or “exhaustion” of T cells specific to the virus, a condition also observed in T cells that infiltrate tumors. The exhausted state is associated with poor T cell memory and expression of specific cell-surface proteins, some of which may inhibit T cell activation. Expression of Tim-3 is associated with acquisition of T cell exhaustion, although it is also expressed transiently during acute infection. We have found that a major function of Tim-3 is to enhance T cell activation during either acute or chronic viral infection, and that Tim-3 is not required for the development of T cell exhaustion.