Apoptosis of mouse naive T cells induced by recombinant soluble Fas ligand and activation-induced resistance to Fas ligand.
We have investigated the susceptibility of mouse T cells at various maturation and activation stages to recombinant soluble mouse Fas ligand (termed WX1). CD4+CD8+ thymocytes were preferentially killed by WX1, although CD4+CD8- and CD4-CD8+ thymocytes were also killed at higher concentrations of WX1. The majority of CD4-CD8- thymocytes were resistant to the same doses of WX1. Naive peripheral T cells were also killed by WX1 at concentrations similar to those for single-positive thymocytes. Activation-induced cell death of previously activated T cells is known to be mediated by Fas and Fas ligand. However, the activation of naive splenic T cells by mAbs against CD3/TCR complex rather induced resistance against WX1. This resistance was induced in activated T cells but not in bystander T cells. These mechanisms seem to explain why activated T cells are not immediately killed and why bystander T cells are not activated in an Ag-nonspecific manner.
Osaka Bioscience Institute, Department of Molecular Biology, Japan.
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Suda
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Tanaka
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Miwa
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Nagata
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D019556:COS Cells; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D004351:Drug Resistance; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008817:Mice, Mutant Strains; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D014162:Transfection
D018076:DNA, Complementary; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011993:Recombinant Fusion Proteins