Increases in inflammation, coagulation, and CD8 T cell numbers are associated with elevated cardiovascular disease (CVD) risk in antiretroviral therapy (ART)-treated HIV infection. Circulating memory CD8 T cells that express the vascular endothelium-homing receptor CX3CR1 (fractalkine receptor) are enriched in ART-treated HIV-infected subjects. Thrombin-activated receptor (PAR-1) expression is increased in ART-treated HIV-infected subjects and is particularly elevated on CX3CR1+ CD8 T cells, suggesting that these cells could interact with coagulation elements. Indeed, thrombin directly enhanced T cell receptor mediated IFNγ production by purified CD8 T cells, but was attenuated by thrombin-induced release of TGF-β by platelets. We have therefore identified a population of circulating memory CD8 T cells in HIV infection that may home to endothelium, can be activated by clot-forming elements, and are susceptible to platelet-mediated regulation. Complex interactions between inflammatory elements and coagulation at endothelial surfaces may play an important role in CVD risk in ART-treated HIV-infected individuals.
Inflammatory function of CX3CR1+ CD8 T cells in treated HIV infection is modulated by platelet interactions.