Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein

Johnson T.P.; Patel K.; Johnson K.R.Maric D.Calabresi P.A.Hasbun R.Nath A.

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Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein

机译：Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein

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Chronic immune activation is a major complication of antiretroviral therapy (ART) for HIV infection and can cause a devastating immune reconstitution inflammatory syndrome (IRIS) in the brain. The mechanism of T-cell activation in this population is not well understood. We found HIV-Tat protein and IL-17-expressing mononuclear cells in the brain of an individual with IRIS. Tat was also present in the CSF of individuals virologically controlled on ART. Hence we examined if Tat protein could directly activate T cells. Tat transcriptionally dysregulated 94 genes and induced secretion of 11 cytokines particularly activation of IL-17 signaling pathways supporting the development of a proinflammatory state. Tat increased IL-17 transcription and secretion in T cells. Tat entered the T cells rapidly by clathrin-mediated endocytosis and localized to both the cytoplasm and the nucleus. Tat activated T cells through a nonclassical pathway dependent upon vascular endothelial growth factor receptor-2 and downstream secondary signaling pathways but independent of the T-cell receptor. However, Tat stimulation of T cells did not induce T-cell proliferation but increased viral infectivity. This study demonstrates Tat's role as a virulence factor, by driving T-cell activation and contributing to IRIS pathophysiology. This supports the necessity of an anti-Tat therapy in conjunction with ART and identifies multiple targetable pathways to prevent Tat-mediated T-cell activation.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第33期|13588-13593|共6页
作者
Johnson T.P.; Patel K.; Johnson K.R.Maric D.Calabresi P.A.Hasbun R.Nath A.;
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作者单位

Section of Infections of the Nervous System, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, United States;

Department of Neurology, Johns Hopkins University, Baltimore, MD 21287, United States;

Department of Internal Medicine, University of Texas Health Science Center, Houston, TX 77030, United States;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Central nervous system; Chromatin; Chronic inflammation; CNS inflammation; Lymphocyte;

Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein

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