The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance

Immunity. 1996 Mar;4(3):321-8. doi: 10.1016/s1074-7613(00)80440-9.


Using cells from TCR transgenic mice that do or do not express Fas, we show that there are two mechanistically distinct forms of apoptosis in CD4+ T cells. Naive T cells undergo apoptosis if cultured in the absence of antigen or costimulation. This form of programmed cell death (PCD) is not dependent on Fas, and is prevented by CD28-mediated signals, which lead to the secretion of growth factors and the expression of survival genes, such as bcl-xL. Recently activated T cells undergo apoptotic death upon repeated stimulation. This activation-induced cell death (AICD) is mediated by Fas, but is independent of costimulation and is not prevented by IL-2 or bcl-xL. Finally, we show that peripheral tolerance may be induced in vivo independent of Fas-mediated cell death.

Publication types

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

MeSH terms

  • Animals
  • Antigen Presentation* / genetics
  • Apoptosis / immunology*
  • CD28 Antigens / physiology
  • CD4-Positive T-Lymphocytes / immunology*
  • Clonal Deletion
  • Fas Ligand Protein
  • Gene Expression Regulation / immunology
  • Immune Tolerance* / genetics
  • Ligands
  • Lymphocyte Activation*
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Transgenic
  • Proto-Oncogenes / immunology
  • Signal Transduction / immunology
  • fas Receptor / genetics
  • fas Receptor / physiology*


  • CD28 Antigens
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Ligands
  • Membrane Glycoproteins
  • fas Receptor