TRAIL/Apo-2-ligand-induced apoptosis in human T cells.
Members of the tumor necrosis factor (TNF) family such as CD95 (APO-1/Fas) ligand (L) trigger apoptosis in lymphoid cells. Recently, a new member of apoptosis-inducing ligands, TRAIL (TNF-related-apoptosis-inducing-ligand)/Apo-2 ligand, was identified that might act in a similar way. We compared TRAIL and CD95L-induced apoptosis in human lymphoid cells. Expression of TRAIL was found in CD4+ and CD8 T cells following activation, suggesting that TRAIL participates in T cell-mediated induction of apoptosis. Similar to CD95L, TRAIL-induced apoptosis in target cells is mediated by activation of caspases (ICE/Ced-3 proteases). However, different human lymphoid cell lines and peripheral T cells differ in sensitivity towards induction of apoptosis by TRAIL and CD95L. In addition, T cells are highly sensitive towards CD95L-induced apoptosis after prolonged activation in vitro, but remain completely resistant to TRAIL-induced apoptosis. In contrast, T cells from HIV-1-infected patients previously shown to exhibit increased CD95 sensitivity are even more susceptible towards TRAIL-induced cell death. These data suggest that TRAIL might participate in CD95-independent apoptosis of lymphoid cells and might be involved in deregulated apoptosis in diseases such as leukemias and HIV-1 infection.
Jeremias
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Division of Molecular Oncology/Pediatrics, German Cancer Research Center, Heidelberg.
Herr
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Boehler
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Debatin
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KM
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003546:Cysteine Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D015497:HIV-1; D006801:Humans; D007223:Infant; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1