Extensive and preferential Fas/Fas ligand-dependent death of γδ T cells following infection with Listeria monocytogenes

Abstract

In the spleens of mice infected intraperitoneally with the bacterium Listeria monocytogenes, both αβ and γδ T cells became rapidly activated, followed by a massive apoptotic death response predominantly within the γδ population. The death response involved two major splenic γδ T-cell subsets and was Fas/Fas ligand (Fas-L)-dependent. Among T cells isolated from the Listeria-infected spleen, Fas-L was almost exclusively expressed in γδ T cells. γδ T cells coexpressed Fas and Fas-L, suggesting activation-induced suicide as a mechanism of their death. In vivo treatment with an antibody specific for CD3ε induced activation, preferential Fas-L expression and apoptosis of γδ T cells, resembling the response pattern in listeriosis, whereas antibodies specific for T-cell receptor-β (TCR-β) or TCR-δ did not, suggesting that the complete response seen in listeriosis requires both γδ TCR engagement and additional stimuli. L. monocytogenes causes early nonspecific, Fas-independent lymphocyte death in heavily infected tissues. In contrast, the death response described here is selective, Fas-dependent and triggered at low local levels of bacteria, suggesting that it is controlled by interactions with other infection-activated host cells, and perhaps part of a regulatory circuit specifically curtailing γδ T cells.