@article{2814,
  keywords = {Antibodies, Monoclonal, CD3 Complex, Cell Division, Coculture Techniques, Dose-Response Relationship, Drug, Flow Cytometry, Humans, Immunoblotting, Membrane Proteins, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Neutrophils, Oxidative Stress, Phosphorylation, Reactive Oxygen Species, Receptors, Antigen, T-Cell, Signal Transduction, Time Factors},
  author = {Cemerski S and Cantagrel A and Van Meerwijk JP M and Romagnoli P},
  title = {Reactive oxygen species differentially affect T cell receptor-signaling pathways.},
  abstract = {<p>Oxidative stress plays an important role in the induction of T lymphocyte hyporesponsiveness observed in several human pathologies including cancer, rheumatoid arthritis, leprosy, and AIDS. To investigate the molecular basis of oxidative stress-induced T cell hyporesponsiveness, we have developed an in vitro system in which T lymphocytes are rendered hyporesponsive by co-culture with oxygen radical-producing activated neutrophils. We have observed a direct correlation between the level of T cell hyporesponsiveness induced and the concentration of reactive oxygen species produced. Moreover, induction of T cell hyporesponsiveness is blocked by addition of N-acetyl cysteine, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, and catalase, confirming the critical role of oxidative stress in this system. The pattern of tyrosine-phosphorylated proteins was profoundly altered in hyporesponsive as compared with normal T cells. In hyporesponsive T cells, T cell receptor (TCR) ligation no longer induced phospholipase C-gamma1 activation and caused reduced Ca(2+) flux. In contrast, despite increased levels of ERK1/2 phosphorylation, TCR-dependent activation of mitogen-activated protein kinase ERK1/2 was unaltered in hyporesponsive T lymphocytes. A late TCR-signaling event such as caspase 3 activation was as well unaffected in hyporesponsive T lymphocytes. Our data indicate that TCR-signaling pathways are differentially affected by physiological levels of oxidative stress and would suggest that although "hyporesponsive" T cells have lost certain effector functions, they may have maintained or gained others.</p>},
  year = {2002},
  journal = {The Journal of biological chemistry},
  volume = {277},
  pages = {19585-93},
  month = {2002 May 31},
  issn = {0021-9258},
  doi = {10.1074/jbc.M111451200},
  language = {eng},
}