Biochemical mechanisms of IL-2-regulated Fas-mediated T cell apoptosis

Immunity. 1998 May;8(5):615-23. doi: 10.1016/s1074-7613(00)80566-x.


Activation-induced cell death (AICD) of lymphocytes is an important mechanism of self-tolerance. In CD4+ T cells, AICD is mediated by the Fas pathway and is enhanced by IL-2. To define the mechanisms of this pro-apoptotic action of IL-2, we analyzed CD4+ T cells from wild-type and IL-2-/- mice expressing a transgenic T cell receptor. T cells become sensitive to AICD after activation by antigen and IL-2. IL-2 increases transcription and surface expression of Fas ligand (FasL) and suppresses transcription and expression of FLIP, the inhibitor of apoptosis. The ability of IL-2 to enhance expression of a pro-apoptotic molecule, FasL, and to suppress an inhibitor of Fas signaling, FLIP, likely accounts for the role of this cytokine in potentiating T cell apoptosis.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Antigens, Surface / immunology
  • Apoptosis / immunology*
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CD4-Positive T-Lymphocytes / immunology*
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Fas Ligand Protein
  • Fas-Associated Death Domain Protein
  • Immune Tolerance
  • Interleukin-2 / physiology*
  • Intracellular Signaling Peptides and Proteins*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Mice
  • Transcriptional Activation
  • fas Receptor / immunology*


  • Adaptor Proteins, Signal Transducing
  • Antigens, Surface
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Carrier Proteins
  • Cflar protein, mouse
  • Fadd protein, mouse
  • Fas Ligand Protein
  • Fas-Associated Death Domain Protein
  • Fasl protein, mouse
  • Interleukin-2
  • Intracellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • fas Receptor