Selective up-regulation of phosphatidylinositol 3'-kinase activity in Th2 cells inhibits caspase-8 cleavage at the death-inducing complex: A mechanism for Th2 resistance from Fas-mediated apoptosis

Arun S. Varadhachary, Marcus E. Peter, Somia N. Perdow, Peter H. Krammer, Padmini Salgame

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

In this study the mechanism of differential sensitivity of CD3-activated Th1- and Th2-type cells to Fas-mediated apoptosis was explored. We show that the Fas-associated death domain protein (FADD)/caspase-8 pathway is differentially regulated by CD3 activation in the two subsets. The apoptosis resistance of activated Th2-type cells is due to an incomplete processing of caspase-8 at the death-inducing signaling complex (DISC) whereas recruitment of caspase-8 to the DISC of Th1- and Th2-like cells is comparable. Activation of phosphotidylinositol 3'-kinase upon ligation of CD3 in Th2-type cells blocked caspase-8 cleavage to its active fragments at the DISC, thereby preventing induction of apoptosis. This study offers a new pathway for phosphotidylinositol 3'-kinase in mediating protection from Fas-induced apoptosis.

Original languageEnglish
Pages (from-to)4772-4779
Number of pages8
JournalJournal of Immunology
Volume163
Issue number9
StatePublished - Nov 6 1999
Externally publishedYes

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