Abstract
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*
Substances
-
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