Differential requirement of caspases during naive T cell proliferation

Eur J Immunol. 2002 Oct;32(10):3007-15. doi: 10.1002/1521-4141(2002010)32:10<3007::AID-IMMU3007>3.0.CO;2-9.


The involvement of Fas and caspase activation during naive T cell proliferation is still controversial. To explore this paradox, we used antigenic variation of PCC 88-104 peptide to dissect pathways of TCR signaling leading to cell proliferation. We demonstrated that strong TCR stimulation but not weak TCR stimulation induced T cell proliferation and was dependent on IETD- but independent of DEVD-specific caspases. In addition, altered TCR ligand induced T cell proliferation in the absence of IETD-, DEVD-specific caspase activities and Fas ligand expression. However, AND-TCR-transgenic mice in lpr/lpr background generated recently have no defect T cell proliferation after stimulation by the agonist peptide, demonstrating that antigen-induced T cell proliferation is independent of Fas-activation pathways. Thus, Fas-independent caspase activation is tightly regulated by the strength of antigenic stimulation during T cell proliferation. These data reveal a novel facet of antigenic caspase regulation during naive CD4 T cell proliferation and provide insights into the function of caspases during T cell homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Caspase Inhibitors
  • Caspases / physiology*
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Fas Ligand Protein
  • Female
  • Interleukin-2 / biosynthesis
  • Lymphocyte Activation*
  • Male
  • Membrane Glycoproteins / analysis
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Receptors, Antigen, T-Cell / physiology
  • T-Lymphocytes / immunology*


  • Caspase Inhibitors
  • Enzyme Inhibitors
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Interleukin-2
  • Membrane Glycoproteins
  • Receptors, Antigen, T-Cell
  • Caspases