Inflammatory Function of CX3CR1+ CD8+ T Cells in Treated HIV Infection Is Modulated by Platelet Interactions.

Abstract

Increases in inflammation, coagulation, and CD8⁺ T-cell numbers are associated with an elevated cardiovascular disease (CVD) risk in human immunodeficiency virus (HIV)-infected antiretroviral therapy (ART) recipients. Circulating memory CD8⁺ T cells that express the vascular endothelium-homing receptor CX3CR1 (fractalkine receptor) are enriched in HIV-infected ART recipients. Thrombin-activated receptor (PAR-1) expression is increased in HIV-infected ART recipients 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 interferon γ production by purified CD8⁺ T cells but was attenuated by thrombin-induced release of transforming growth factor 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 HIV-infected ART recipients.