Selective up-regulation of phosphatidylinositol 3′-kinase activity in Th2 cells inhibits caspase-8 cleavage at the death-inducing complex

• Verfasst von: Varadhachary, Arun S. [VerfasserIn]
• Verfasst von: Peter, Marcus E. [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: Selective up-regulation of phosphatidylinositol 3′-kinase activity in Th2 cells inhibits caspase-8 cleavage at the death-inducing complex
• Titelzusatz: a mechanism for Th2 resistance from fas-mediated apoptosis
• Verf.angabe: Arun S. Varadhachary, Marcus E. Peter, Somia N. Perdow, Peter H. Krammer, and Padmini Salgame
• E-Jahr: 1999
• Jahr: November 1, 1999
• Umfang: 8 S.
• Teil: volume:163
• Teil: year:1999
• Teil: number:9
• Teil: pages:4772-4779
• Teil: extent:8
• Fussnoten: Gesehen am 26.04.2021
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 1999
• Band/Heft Quelle: 163(1999), 9, Seite 4772-4779
• ISSN Quelle: 1550-6606
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1755908598

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 phosphatidylinositol 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 phosphatidylinositol 3′-kinase in mediating protection from Fas-induced apoptosis.