Expression of TRAIL receptors in human autoreactive and foreign antigen-specific T cells.
Deletion of T cells due to apoptosis induction is a regulatory mechanism in the human immune system that may be impaired in autoimmune diseases such as multiple sclerosis (MS). Involvement of the apoptosis-mediating CD95/CD95 ligand system in MS has been demonstrated. Here, we report that (auto)antigen-specific human T cells are not killed in vitro by soluble TNF-related apoptosis-inducing ligand (TRAIL) although expressing death-inducing receptors, TRAIL receptor 1 (TRAIL-R1) and TRAIL-R2. Apoptosis was assessed by caspase activation and DNA fragmentation, receptor expression was detected by RT - PCR and flow cytometry. The (auto)antigen-specific T cells were also resistant to specific TRAIL-R1/TRAIL-R2-directed induction of apoptosis, indicating that coexpression of the truncated TRAIL-R3 and TRAIL-R4 in these T cells is not responsible for the observed resistance. Upon stimulation, levels of death-inducing TRAIL receptors decreased whereas TRAIL was up-regulated on the cell surface. In contrast to CD95, the role of TRAIL receptors in MS might not involve regulation of T cell vulnerability.
Wendling
U
U
Department of Neurology, Division of Neuroimmunology, Charité, Berlin, Germany.
Walczak
H
H
Dörr
J
J
Jaboci
C
C
Weller
M
M
Krammer
P H
PH
Zipp
F
F
D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D053938:DNA Fragmentation; D058851:GPI-Linked Proteins; D005910:Glioma; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D013745:Tetanus Toxoid / Q000276:immunology; D014407:Tumor Cells, Cultured; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; D001324:Autoantigens; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C108661:TNFRSF10C protein, human; C505653:TNFSF10 protein, human; D013745:Tetanus Toxoid; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D020169:Caspases