Differential requirement of caspases during naive T cell proliferation.
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.
D000595:Amino Acid Sequence; D000818:Animals; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein; D005260:Female; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D020169:Caspases