A subclass of dendritic cells kills CD4 T cells via Fas Fas-ligand-induced apoptosis

Dendritic cells (DC), the most efficient antigen-presenting cells, are well equipped for activation of naive CD4(+) T cells by their expression of high levels of major histocompatibility complex and costimulator molecules. We now demonstrate that some DC are equally well equipped for killing these same T cells. Murine splenic DC consist of both conventional CD8 alpha(-) DC and a major population of CD8 alpha(+) DC. Whereas CD8(-) DC induce a vigorous proliferative response in CD4 T cells, CD8(+) DC induce a lesser response that is associated with marked T cell apoptosis. By using various mixtures of T cells and DC from Fas-mutant lpr/lpr mice and Fas-ligand (FasL) mutant gld/gld mice, we show this death is due to interaction of Fas on activated T cells with Fast on CD8(+) DC. Furthermore, we show by direct surface staining that CD8(+) DC, but not CD8(-) DC, express FasL at high levels. These findings indicate that FasL(+) CD8(+) DC are a specialized subgroup of DC with a role in the regulation of the response of primary peripheral T cells.