FP15-1 Chemical crosstalk between human fat cells and memory CD4+ T cells increase T cell activation and HIV production

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP15-Adipocyte Biology
Bench to Bedside
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:45 AM
Room 303 (Moscone Center)

Poster Board SUN-666
Jacob Couturier*1, David J Luke2, Ashok Balasubramanyam3 and Dorothy E Lewis1
1University of Texas Health Science Center at Houston, Houston, TX, 2Baylor College of Medicine, Houston, TX, 3Baylor Coll of Med, Houston, TX
HIV lipodystrophy, obesity, and metabolic syndrome are associated with defective adipose physiology, and increased numbers of CD4 T cells and macrophages in adipose tissues.  CD4 T cells and macrophages are the primary host cells for HIV, and HIV-infected immune cells and fat cells may interact in ways that cause adipose dysfunction as well as regulate immune cell functions and HIV replication. Adipose depots contain cytokines, chemokines, and adipokines that could regulate immune cell functions and the HIV life cycle. Activated memory CD4+CD45RO+CD69+ T cells are present in adipose tissues and such a phenotype would be conducive for HIV replication. Conversely, soluble, virion-free viral proteins such as Vpr and Nef could be released from infected memory CD4 T cells or macrophages and cause adipocyte defects such as lipolysis, impaired adipogenesis, and apoptosis.

To investigate interactions between fat cells and HIV-infected memory CD4 T cells, purified human memory CD4+ T cells were infected with HIV in vitro and cocultured in transwells with primary subcutaneous preadipocytes or mature adipocytes for up to 1 week. CD4 T cell functions known to regulate HIV replication such as activation, proliferation, and survival were examined by flow cytometry. Both preadipocytes and adipocytes enhanced T cell activation and HIV production within 3-6 days of coculture. The enhanced CD4 T cell activation and increased HIV production were mediated by IL6 and integrin ligands from preadipocytes and adipocytes. Intriguingly, there was an absolute requirement for common γ-chain cytokines IL2, IL7, or IL15 (exogenously added to cocultures), which are important for homeostatic stimulation and survival of memory T cells. IL7 and IL15 mRNA expression (but not IL2 mRNA) was detected in preadipocytes and adipocytes. Interestingly, mature adipocytes expressed both IL15 and IL15-receptor-α protein on their cell surfaces, but did not secrete IL15 into the medium, suggesting that adipocytes may “trans-present” IL15 to HIV-infected CD4 T cells via cell contact, and thus engender the signals that enhance HIV replication. Both uninfected and HIV-infected memory CD4 T cells also inhibited adipogenesis. These results demonstrate key interactions between HIV-infected memory CD4 T cells and fat cells that increase T cell activation and HIV replication with a block in adipogenesis.

Nothing to Disclose: JC, DJL, AB, DEL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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