Single-cell analysis of adipose tissue T cells in diabetic persons with HIV reveals high proportions of clonally expanded CMV-like CD4+ T cells with cytotoxic RNA transcriptomes

Persons with HIV have a disproportionate burden of metabolic disease, including type 2 diabetes. We hypothesized that the accumulation of chronically activated T cells in the adipose tissue of HIV+ persons is a central mechanism promoting local macrophage activation, impaired adipocyte function, and the development of HIV-associated glucose intolerance. Prior studies of immune activation and HIV-associated metabolic disease have only measured circulating T cell subsets. In contrast, in our study we recruited a longitudinal cohort of HIV+ patients on antiretroviral therapy ranging from insulin sensitive to overtly diabetic, in addition to HIV-negative diabetic controls, to identify potential mechanistic linkages between adipose-resident T cell cytokine signaling, adipose tissue inflammation, and glucose intolerance in HIV+ persons. This study may also provide further insight into the role of T cells in the development of glucose intolerance in HIV-negative patients. Overall design: Subcutaneous adipose tissue and matched peripheral blood CD3+ memory T cells were analyzed from diabetic, non-diabetic persons with HIV and diabetic HIV-negative persons for a total of 16 subjects - 32 samples