Human adipose tissue as a reservoir for memory CD4⁺ T cells and HIV

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 andHIV-infected persons, but the AT-SVF CD4⁺/CD8⁺ ratiowas lower in HIV patients. HIVDNA(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 gammachain cytokines interleukin (IL)-2, IL7 or IL15. These effects were mitigated by neutralizing antibodies against IL6 and integrin-a1b1. 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.