T cells are key mediators of intestinal immunity, and specific T cell subsets can have differing immunoregulatory roles in animal models of mucosal inflammation. In this study, we describe human CD56+ T cells as a morphologically distinct population expressing a mature, nonproliferative phenotype that is frequent in the gut. Enhanced potential for IFN-gamma and TNF synthesis suggested a proinflammatory function, and we directly demonstrate effector function mediated by direct T-T interaction with responder cells in vitro. CD56+ T cells from peripheral blood responded to the gut-related CD2 signal, and were necessary for effective CD2-mediated proliferation of peripheral blood CD56- T cells. Our findings associate CD56+ T cells with the intestinal immune compartment and suggest a putative effector function in human mucosal immunity.