Abstract
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. Cell Death and Differentiation (2000) 7, 637–644
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Abbreviations
- TRAIL:
-
TNF-related apoptosis-inducing ligand
- Trail-R:
-
TRAIL receptor
- MS:
-
Multiple Sclerosis
- EAE:
-
experimental autoimmune encephalomyelitis
- MBP:
-
myelin basic protein
- TT:
-
tetanus toxoid
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Acknowledgements
We thank Ulrike Grieger, Heiko Stahl and Eva Rieser for expert technical assistance and Orhan Aktas for help with preparing the manuscript. F Zipp was supported by grants from the Deutsche Forschungsgemeinschaft ZI 448/7-1, the Gemeinnützige Hertie-Stiftung, and the Deutsche Multiple Sklerose-Gesellschaft. H Walczak received a fellowship from the Bundesministerium für Forschung und Technologie (AIDS-Stipendium).
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Wendling, U., Walczak, H., Dörr, J. et al. Expression of TRAIL receptors in human autoreactive and foreign antigen-specific T cells. Cell Death Differ 7, 637–644 (2000). https://doi.org/10.1038/sj.cdd.4400692
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DOI: https://doi.org/10.1038/sj.cdd.4400692
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