Abstract In people living with HIV (PLWH), immune activation and systemic inflammation are associated with cardiovascular risk independently of the traditional risk factors or duration of antiretroviral treatment and CD4 counts. Endothelial inflammation and injury play a critical role in the pathogenesis of cardiovascular risk/disease. Recent reports had shown that T cells can promote vascular repair by secretion of proangiogenic factors. Because of these functional properties these T cells are called angiogenic T cells (Tang) and are defined by expression of CXCR4 and CD31. Accordantly, we found that in vitro, TCR stimulated CD8 Tang from healthy volunteers induced secretion of proangiogenic cytokines including angiopoietin-2, fibroblast growth factor, and vascular endothelial growth factor (VEGF) by HUVECs. Because HIV chronic infection drives T cell immune activation, we hypothesized that HIV infection alters Tang’s proangiogenic function. To address this question, we studied the phenotype and function of Tang in PBMCs from PLWH and healthy volunteers. We found that PLWH had a significant decrease in the proportion of both CD4 and CD8 Tang when compared to healthy controls, and this difference was more striking in the CD8 Tang. CD8 Tang from PLWH had an activated phenotype and showed an increased expression of granzymes (A and B) when compared to healthy controls. In PLWH, the frequency of GZA+GZB+CD8 Tang was positively associated with 10yr cardiovascular risk score. In addition, upon TCR stimulation, CD8 Tang from PLWH showed a diminished ability to secrete VEGF. These results suggest that in the context of HIV infection, CD8 Tang possesses a pro-inflammatory potential and reduced proangiogenic function to promote endothelial repair.
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