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
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 resis...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
November 1, 1999
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| In: |
The journal of immunology
Year: 1999, Volume: 163, Issue: 9, Pages: 4772-4779 |
| ISSN: | 1550-6606 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://www-jimmunol-org.ubproxy.ub.uni-heidelberg.de/content/163/9/4772
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| Author Notes: | Arun S. Varadhachary, Marcus E. Peter, Somia N. Perdow, Peter H. Krammer, and Padmini Salgame |
| Summary: | 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. |
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| Item Description: | Gesehen am 26.04.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1550-6606 |