Adipose Tissue is Enriched for Activated and Late-Differentiated CD8⁺ T Cells and Shows Distinct CD8⁺ Receptor Usage, Compared With Blood in HIV-Infected Persons

Background: 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. Methods: We recruited 10 HIV-infected, non-diabetic, overweight or obese adults on efavirenz, tenofovir, and emtricitabine for >4 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. Results: Adipose tissue had a higher percentage of CD3⁺CD8⁺ T cells compared with blood (61.0% vs. 51.7%, P < 0.01) and was enriched for both activated CD8⁺HLA-DR⁺ T cells (5.5% vs. 0.9%, P < 0.01) and late-differentiated CD8⁺CD57⁺ T cells (37.4% vs. 22.7%, P < 0.01). Adipose tissue CD8⁺ T cells displayed distinct TCRb V and J gene usage, and the Shannon Entropy index, a measure of overall TCRb repertoire diversity, was lower compared with blood (4.39 vs. 4.46; P = 0.05). Conclusions: 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.