Uncoupling IL-2 signals that regulate T cell proliferation, survival, and Fas-mediated activation-induced cell death.
IL-2 is an important growth and survival factor for T lymphocytes but also sensitizes these cells to Fas-mediated activation-induced cell death (AICD). The molecular basis of these different effects of IL-2 was studied by introducing wild-type and mutant forms of the IL-2 receptor beta (IL-2Rbeta) chain that lacked specific signaling capacities into receptor-deficient T cells by retroviral gene transfer. Activation of Stat5 by IL-2 was found to be involved in T cell proliferation and promoted Fas ligand (FasL) expression and AICD. T cell survival was dependent on a receptor region that activated Akt and the expression of Bcl-2. Thus, distinct IL-2Rbeta chain signaling modules regulate T cell fate by stimulating growth and survival or by promoting apoptosis.
Van Parijs
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L
Department of Biology, California Institute of Technology, Pasadena 91125, USA.
Refaeli
Y
Y
Lord
J D
JD
Nelson
B H
BH
Abbas
A K
AK
Baltimore
D
D
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016296:Mutagenesis; D015375:Receptors, Interleukin-2 / Q000235:genetics; D012190:Retroviridae; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D019014:fas Receptor / Q000276:immunology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D019014:fas Receptor