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We found that pathophysiological hypoxia (&lt;2% O<jats:sub>2<\/jats:sub>) significantly decreased CD4<jats:sup>+<\/jats:sup> T\u2010cell survival after mitogenic stimulation. This effect was not due to an increased caspase\u20103\/7\u2010mediated apoptosis or adenosine\u20105\u2032\u2010triphosphate (ATP) consumption\/depletion. However, the ability of stimulated T cells to proliferate was reduced under hypoxic conditions, despite increased expression of CD25. Pathophysiological hypoxia was also found to modify intracellular ROS (iROS) levels in stimulated T cells over time as compared with levels found in normoxia. Physiological hypoxia (5% O<jats:sub>2<\/jats:sub>) did not decrease CD4<jats:sup>+<\/jats:sup> T\u2010cell survival and proliferation or modify iROS levels as compared with normoxia. We conclude that pathophysiological hypoxia affects T\u2010cell proliferation and viability via disturbed IL\u20102R signalling downstream of STAT5a phosphorylation, but not as a result of impaired cellular energy homeostasis. We suggest iROS links early events in T\u2010cell stimulation to the inhibition of the lymphoproliferative response under pathophysiological hypoxic conditions. The level of iROS may therefore act as a mediator of immune functions leading to down\u2010regulation of long\u2010term T\u2010cell activity in inflamed tissues.<\/jats:p>","DOI":"10.1002\/eji.201242754","type":"journal-article","created":{"date-parts":[[2013,3,20]],"date-time":"2013-03-20T12:42:05Z","timestamp":1363783325000},"page":"1588-1597","source":"Crossref","is-referenced-by-count":17,"title":["Pathophysiological hypoxia affects the redox state and IL\u20102 signalling of human CD4<sup>+<\/sup> T cells and concomitantly impairs survival and proliferation"],"prefix":"10.1002","volume":"43","author":[{"given":"Timo","family":"Gaber","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology Charit\u00e9 University Hospital  Berlin Germany"},{"name":"German Rheumatism Research Center (DRFZ)  Berlin Germany"},{"name":"Berlin\u2010Brandenburg Center for Regenerative Therapies (BCRT)  Berlin 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