Uncoupling IL-2 signals that regulate T cell proliferation, survival, and Fas-mediated activation-induced cell death

Immunity. 1999 Sep;11(3):281-8. doi: 10.1016/s1074-7613(00)80103-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Retracted Publication

MeSH terms

  • Animals
  • Apoptosis / immunology*
  • Cell Division
  • Cell Survival
  • Cells, Cultured
  • Fas Ligand Protein
  • Gene Transfer Techniques
  • Genetic Vectors
  • Humans
  • Interleukin-2 / immunology*
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation
  • Membrane Glycoproteins / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mutagenesis
  • Receptors, Interleukin-2 / genetics
  • Retroviridae
  • Signal Transduction / immunology*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • fas Receptor / immunology*


  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Interleukin-2
  • Membrane Glycoproteins
  • Receptors, Interleukin-2
  • fas Receptor