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Adipose Tissue is Enriched for Activated and Late-Differentiated CD8+ T Cells and Shows Distinct CD8+ Receptor Usage,
John R Koethe1,2, Wyatt McDonnell3,4, Arion Kennedy5
1Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, TN.
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 CD3CD8 T cells compared with blood (61.0% vs. 51.7%, P < 0.01) and was enriched for both activated CD8HLA-DR T cells (5.5% vs. 0.9%, P < 0.01) and late-differentiated CD8CD57 T cells (37.4% vs. 22.7%, P < 0.01). 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).
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.