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

Jacob Couturier, James W. Suliburk, Jeremy M. Brown, David J. Luke, Neeti Agarwal, Xiaoying Yu, Chi Nguyen, Dinakar Iyer, Claudia A. Kozinetz, Paul A. Overbeek, Michael L. Metzker, Ashok Balasubramanyam, Dorothy E. Lewis

Research output: Contribution to journalArticle

55 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)667-674
Number of pages8
JournalAIDS
Volume29
Issue number6
DOIs
StatePublished - Mar 27 2015

Keywords

  • Adipose tissue
  • Cytokines
  • HIV replication
  • HIV reservoir
  • Memory CD4 T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Couturier, J., Suliburk, J. W., Brown, J. M., Luke, D. J., Agarwal, N., Yu, X., Nguyen, C., Iyer, D., Kozinetz, C. A., Overbeek, P. A., Metzker, M. L., Balasubramanyam, A., & Lewis, D. E. (2015). Human adipose tissue as a reservoir for memory CD4+ T cells and HIV. AIDS, 29(6), 667-674. https://doi.org/10.1097/QAD.0000000000000599