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Although its modes of action on the innate immune system are well described, there is still insufficient knowledge about its direct effects on the adaptive immune system. Thus, we evaluated the influence of CQ on activation parameters of human CD4<jats:sup>+<\/jats:sup>T-cells. CQ directly suppressed proliferation, metabolic activity and cytokine secretion of T-cells following anti-CD3\/anti-CD28 activation. In contrast, CQ showed no effect on up-regulation of T-cell activation markers. CQ inhibited activation of all T helper cell subsets, although IL-4 and IL-13 secretion by Th2 cells were less influenced compared to other Th-specific cytokines. Up to 10\u2009\u03bcM, CQ did not reduce cell viability, suggesting specific suppressive effects on T-cells. These properties of CQ were fully reversible in re-stimulation experiments. Analyses of intracellular signaling showed that CQ specifically inhibited autophagic flux and additionally activation of AP-1 by reducing phosphorylation of c-JUN. This effect was mediated by inhibition of JNK catalytic activity. In summary, we characterized selective and reversible immunomodulatory effects of CQ on human CD4<jats:sup>+<\/jats:sup>T-cells. These findings provide new insights into the biological actions of JNK\/AP-1 signaling in T-cells and may help to expand the therapeutic spectrum of CQ.<\/jats:p>","DOI":"10.1038\/srep42191","type":"journal-article","created":{"date-parts":[[2017,2,7]],"date-time":"2017-02-07T10:38:49Z","timestamp":1486463929000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Chloroquine inhibits human CD4+ T-cell activation by AP-1 signaling modulation"],"prefix":"10.1038","volume":"7","author":[{"given":"Ralf L. 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