Inhibition of T cell apoptosis by IFN-beta rapidly reverses nuclear translocation of protein kinase C-delta. uri icon

abstract

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

published proceedings

  • Eur J Immunol

altmetric score

  • 3

author list (cited authors)

  • Scheel-Toellner, D., Pilling, D., Akbar, A. N., Hardie, D., Lombardi, G., Salmon, M., & Lord, J. M.

citation count

  • 84

complete list of authors

  • Scheel-Toellner, D||Pilling, D||Akbar, AN||Hardie, D||Lombardi, G||Salmon, M||Lord, JM

publication date

  • August 1999

publisher