|Title||Human adipose tissue as a reservoir for memory CD4+ T cells and HIV.|
|Publication Type||Journal Article|
|Year of Publication||2015|
|Authors||Couturier, J, Suliburk, JW, Brown, JM, Luke, DJ, Agarwal, N, Yu, X, Nguyen, C, Iyer, D, Kozinetz, CA, Overbeek, PA, Metzker, ML, Balasubramanyam, A, Lewis, DE|
|Date Published||2015 Mar 27|
|Keywords||Adipocytes, Adipose Tissue, CD4-Positive T-Lymphocytes, Cells, Cultured, Coculture Techniques, DNA, Viral, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, HIV, Humans, Lymphocyte Activation, T-Lymphocyte Subsets|
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.
|PubMed Central ID||PMC4389783|
|Grant List||1R01DK081553 / DK / NIDDK NIH HHS / United States |
5P30AI36211 / AI / NIAID NIH HHS / United States
P30 AI036211 / AI / NIAID NIH HHS / United States
R01 DK081553 / DK / NIDDK NIH HHS / United States
R21 AI116208 / AI / NIAID NIH HHS / United States
R21AI116208 / AI / NIAID NIH HHS / United States