CD152 (CTLA-4) determines the unequal resistance of Th1 and Th2 cells against activation-induced cell death by a mechanism requiring PI3 kinase function

P Pandiyan, D Gärtner, O Soezeri… - The Journal of …, 2004 - rupress.org
The Journal of experimental medicine, 2004rupress.org
Survival of antigen-experienced T cells is essential for the generation of adaptive immune
responses. Here, we show that the genetic and antibody-mediated inactivation of CD152
(cytotoxic T lymphocyte antigen 4) in T helper (Th) effector cells reduced the frequency of
nonapoptotic cells in a completely Fas/Fas ligand (FasL)–dependent manner. CD152 cross-
linking together with stimulation of CD3 and CD28 on activated Th2 cells prevented
activation-induced cell death (AICD) as a result of reduced Fas and FasL expression …
Survival of antigen-experienced T cells is essential for the generation of adaptive immune responses. Here, we show that the genetic and antibody-mediated inactivation of CD152 (cytotoxic T lymphocyte antigen 4) in T helper (Th) effector cells reduced the frequency of nonapoptotic cells in a completely Fas/Fas ligand (FasL)–dependent manner. CD152 cross-linking together with stimulation of CD3 and CD28 on activated Th2 cells prevented activation-induced cell death (AICD) as a result of reduced Fas and FasL expression. Apoptosis protection conferred by CD152 correlated with the up-regulation of Bcl-2 and was mediated by phosphatidylinositol 3 kinase, which prevented FasL expression through the inhibitory phosphorylation of Forkhead transcription factor FKHRL1. We show that signals induced by CD152 act directly on activated T lymphocytes and, due to its differential surface expression on activated Th1 and Th2 cells, induce resistance to AICD mainly in Th2 cells.
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