期刊
AIDS
卷 29, 期 6, 页码 667-674出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000000599
关键词
adipose tissue; cytokines; HIV replication; HIV reservoir; memory CD4(+) T cells
资金
- National Institutes of Health-National Institute of Diabetes and Digestive and Kidney Diseases [1R01DK081553]
- National Institutes of Health-National Institute of Allergy and Infectious Diseases [R21AI116208]
- National Institutes of Health-National Institute of Allergy and Infectious Diseases, Baylor College of Medicine/University of Texas at Houston Center for AIDS Research (CFAR) [5P30AI36211]
Objective: The objective of this study is to determine whether adipose tissue functions as a reservoir for HIV-1. Design: We examined memory CD4(+) T cells and HIV DNA in adipose tissue-stromal vascular fraction (AT-SVF) of five patients [four antiretroviral therapy (ART)-treated and one untreated]. To determine whether adipocytes stimulate CD4(+) T cells and regulate HIV production, primary human adipose cells were cocultured with HIV-infected CD4(+) T cells. Methods: AT-SVF T cells were studied by flow cytometry, and AT-SVF HIV DNA (Gag and Env) was examined by nested PCR and sequence analyses. CD4(+) T-cell activation and HIV production were measured by flow cytometry and ELISA. Results: AT-SVF CD3(+) T cells were activated (>60% CD69(+)) memory CD4(+) and CD8(+) T cells in uninfected and HIV-infected persons, but the AT-SVF CD4(+)/CD8(+) ratio was lower in HIV patients. HIV DNA(Gag and Env) was detected in AT-SVF of all five patients examined by nested PCR, comparably to other tissues [peripheral blood mononuclear cell (PBMC), lymph node or thymus]. In coculture experiments, adipocytes increased CD4(+) T-cell activation and HIV production approximately two to three-fold in synergy with gamma-chain cytokines interleukin (IL)-2, IL7 or IL15. These effects were mitigated by neutralizing antibodies against IL6 and integrin-alpha 1 beta 1. Adipocytes also enhanced T-cell viability. Conclusion: Adipose tissues of ART-treated patients harbour activated memory CD4(+) T cells and HIV DNA. Adipocytes promote CD4(+) T-cell activation and HIV production in concert with intrinsic adipose factors. Adipose tissue may be an important reservoir for HIV. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.
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