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

作者：Koethe John R.^*; McDonnell Wyatt; Kennedy Arion; Abana Chike O.; Pilkinton Mark; Setliff Ian; Georgiev Ivelin; Barnett Louise; Hager Cindy C.; Smith Rita; Kalams Spyros A.; Hasty Alyssa; Mallal Simon

来源：JAIDS: Journal of Acquired Immune Deficiency Syndromes , 2018, 77(2): E14-E21.

• HIV
• obesity
• metabolic disease
• adipose tissue
• T-cell receptor
• clonality

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.

• 出版日期2018-2-1