Single-cell analysis shows that adipose tissue of persons with both HIV and diabetes is enriched for clonal, cytotoxic, and CMV-specific CD4+ T cells

单细胞分析显示,同时患有 HIV 和糖尿病的患者的脂肪组织中富含克隆性、细胞毒性和 CMV 特异性 CD4+ T 细胞。

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作者:Celestine N Wanjalla ,Wyatt J McDonnell ,Ramesh Ram ,Abha Chopra ,Rama Gangula ,Shay Leary ,Mona Mashayekhi ,Joshua D Simmons ,Christian M Warren ,Samuel Bailin ,Curtis L Gabriel ,Liang Guo ,Briana D Furch ,Morgan C Lima ,Beverly O Woodward ,LaToya Hannah ,Mark A Pilkinton ,Daniela T Fuller ,Kenji Kawai ,Renu Virmani ,Aloke V Finn ,Alyssa H Hasty ,Simon A Mallal ,Spyros A Kalams ,John R Koethe

Abstract

Persons with HIV are at increased risk for diabetes mellitus compared with individuals without HIV. Adipose tissue is an important regulator of glucose and lipid metabolism, and adipose tissue T cells modulate local inflammatory responses and, by extension, adipocyte function. Persons with HIV and diabetes have a high proportion of CX3CR1+ GPR56+ CD57+ (C-G-C+) CD4+ T cells in adipose tissue, a subset of which are cytomegalovirus specific, whereas individuals with diabetes but without HIV have predominantly CD69+ CD4+ T cells. Adipose tissue CD69+ and C-G-C+ CD4+ T cell subsets demonstrate higher receptor clonality compared with the same cells in blood, potentially reflecting antigen-driven expansion, but C-G-C+ CD4+ T cells have a more inflammatory and cytotoxic RNA transcriptome. Future studies will explore whether viral antigens have a role in recruitment and proliferation of pro-inflammatory C-G-C+ CD4+ T cells in adipose tissue of persons with HIV.

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