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

TitleHuman adipose tissue as a reservoir for memory CD4+ T cells and HIV.
Publication TypeJournal Article
Year of Publication2015
AuthorsCouturier, 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
JournalAIDS
Volume29
Issue6
Pagination667-74
Date Published2015 Mar 27
ISSN1473-5571
KeywordsAdipocytes, 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
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.

DOI10.1097/QAD.0000000000000599
Alternate JournalAIDS
PubMed ID25849830
PubMed Central IDPMC4389783
Grant List1R01DK081553 / 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