Induction of TRAIL-mediated glioma cell death by human T cells.
Among the death ligands of the tumor necrosis factor/nerve growth factor (TNF/NGF) superfamily, TNF-related apoptosis-inducing ligand (TRAIL) is considered to play a unique role due to its binding to both apoptosis-inducing and -blocking membranous receptors, apoptosis-independent effects and distinct species differences. Here, we demonstrate that human antigen-specific T helper cells upon activation are capable of directly lysing glioma cell lines via TRAIL receptor/TRAIL interactions. Out of 17 T cell lines, nine showed predominantly TRAIL-mediated killing of glioma cell lines compared to CD95 ligand- or TNF-induced cell death. The cytotoxic potential of the T cell lines was independent of T helper differentiation, antigen specificity and donor source. Thus, TRAIL-mediated signaling is involved in T cell cytotoxicity towards glioma cell lines, which might play an important role in tumor regression.
Dörr
Jan
J
Division of Neuroimmunology, Department of Neurology, Charité, Neuroscientific Research Center, 10098, Berlin, Germany.
Waiczies
Sonia
S
Wendling
Uwe
U
Seeger
Bibiane
B
Zipp
Frauke
F
D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins; D001932:Brain Neoplasms; D002454:Cell Differentiation / Q000276:immunology; D000939:Epitopes; D053222:Fas Ligand Protein; D005910:Glioma; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D000939:Epitopes; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha