CX3CR1+ CD8 T cells in treated HIV infection are functionally impaired by platelet interactions (VIR6P.1171)

In the era of highly effective antiretroviral therapy (ART), HIV-infected patients have a better long-term prognosis than ever; however, increased inflammation and coagulation in HIV infection is associated with an increased risk of cardiovascular and other morbidities. CD8 T cell expansion is characteristic of HIV infection and has been linked to increased morbidities especially cardiovascular disease in treated HIV infection. Here we have identified a population of circulating memory CD8 T cells that express the vascular endothelium homing receptor CX3CR1 (fractalkine receptor) and is enriched in ART-treated HIV+ patients. CX3CR1+ CD8 T cells have elevated expression of the platelet-binding receptor PSGL-1 and the thrombin-activated receptor PAR-1, suggesting a possible role in cardiovascular disease via endothelial localization and interactions with platelets and mediators of coagulation. We found that even though thrombin stimulation via PAR-1 could directly enhance CD8 T cell responses in vitro, CD8 T cell cytokine production was diminished in the presence of thrombin-activated platelets through mechanisms mediated in part by TGF-β. Thus, we have identified a population of circulating memory CD8 T cells in HIV infection that are activated by thrombin, are susceptible to platelet-mediated regulation, and could contribute to cardiovascular disease risk in ART-treated HIV-infected patients.