Inhibition of T cell apoptosis by IFN-β rapidly reverses nuclear translocation of protein kinase C-δ

Abstract

Type I interferons rescue activated human T cells from cytokine deprivation‐induced apoptosis. Our data now show that IFN‐β also rapidly inhibits apoptotic signals induced through the Fas receptor (CD95) in human T cells. To identify upstream signaling elements that could be targets of IFN‐β, we have studied protein kinase C (PKC). PKC‐δ is actively involved in the regulation of apoptosis and immunofluorescence staining revealed that early in apoptosis PKC‐δ accumulated in the nucleus. Addition of IFN‐β to T cells already deprived of survival factors or treated with anti‐Fas antibody caused a rapid retranslocation of PKC‐δ away from the nucleus. Furthermore, the generation of a constitutively active catalytic fragment by cleavage of PKC‐δ by caspase 3 occurred only after translocation of full‐length PKC‐δ to the nucleus. IFN‐β also inhibited caspase 3 and the proteolytic activation of PKC‐δ. We conclude from these studies that nuclear translocation of PKC‐δ is an early event in T cell apoptosis and that IFN‐β rapidly reverses this process.