Adipose Tissue is Enriched for Activated and Late-differentiated CD8+ T cells, and Shows Distinct CD8+ Receptor Usage, Compared to Blood in HIV-infected Persons

Adverse viral and medication effects on adipose tissue contribute to the development of metabolic disease in HIV-infected persons, but T cells also have a central role modulating local inflammation and adipocyte function. We sought to characterize potentially proinflammatory T-cell populations in adipose tissue among persons on long-term antiretroviral therapy and assess whether adipose tissue CD8 T cells represent an expanded, oligoclonal population.We recruited 10 HIV-infected, non-diabetic, overweight or obese adults on efavirenz, tenofovir, and emtricitabine for4 years with consistent viral suppression. We collected fasting blood and subcutaneous abdominal adipose tissue to measure the percentage of CD4 and CD8 T cells expressing activation, exhaustion, late differentiation/senescence, and memory surface markers. We performed T-cell receptor (TCR) sequencing on sorted CD8 cells. We compared the proportion of each T-cell subset and the TCR repertoire diversity, in blood versus adipose tissue.Adipose tissue had a higher percentage of CD3CD8 T cells compared with blood (61.0% vs. 51.7%, P0.01) and was enriched for both activated CD8HLA-DR T cells (5.5% vs. 0.9%, P0.01) and late-differentiated CD8CD57 T cells (37.4% vs. 22.7%, P0.01). Adipose tissue CD8 T cells displayed distinct TCRβ V and J gene usage, and the Shannon Entropy index, a measure of overall TCRβ repertoire diversity, was lower compared with blood (4.39 vs. 4.46; P = 0.05).Adipose tissue is enriched for activated and late-differentiated CD8 T cells with distinct TCR usage. These cells may contribute to tissue inflammation and impaired adipocyte fitness in HIV-infected persons.