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aDivision of Infectious Diseases, Department of Internal Medicine, University of Texas Health Science Center at Houston bDepartment of Surgery, Baylor College of Medicine, Houston, Texas cDepartment of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana dDiabetes Research Center, Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Baylor College of Medicine eDepartment of Pediatrics fDepartment of Molecular and Human Genetics gDepartment of Molecular and Cellular Biology, Baylor College of Medicine hEndocrine Service, Ben Taub General Hospital, Houston, Texas, USA.
Published: March 2015
AI Article Synopsis
Article Abstract
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-α1β1. 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.
