Downmodulation of the Inflammatory Response to Bacterial Infection by γδ T Cells Cytotoxic for Activated Macrophages

Although gammadelta T cells are involved in the regulation of inflammation after infection, their precise function is not known. Intraperitoneal infection of T cell receptor (TCR)-delta(-/-) mice with the intracellular bacterium Listeria monocytogenes resulted in the development of necrotic foci in the livers. In contrast, the peritoneal cavities of infected TCR-delta(-/-) mice contained an accumulation of low density activated macrophages and a reduced percentage of macrophages undergoing apoptosis. gammadelta T cell hybridomas derived from mice infected with Listeria were preferentially stimulated by low density macrophages from peritoneal exudates of infected mice. Furthermore, primary splenic gammadelta T cells isolated from Listeria-infected mice were cytotoxic for low density macrophages in vitro, and cytotoxicity was inhibited in the presence of antibodies to the gammadelta TCR. These results demonstrate a novel interaction between gammadelta T cells and activated macrophages in which gammadelta T cells are stimulated by terminally differentiated macrophages to acquire cytotoxic activity and which, in turn, induce macrophage cell death. This interaction suggests that gammadelta T cells regulate the inflammatory response to infection with intracellular pathogens by eliminating activated macrophages at the termination of the response.