Thrombin mediates kinesis in human resting CD8 T cells from healthy controls and HIV infected individuals through specific interaction with thrombin receptor (PAR-1). (112.7)

Abstract

Abstract Chronic infections, such as HIV, are complicated with coagulation abnormalities and increased risk of cardiovascular events, however the mechanisms that link infection/inflammation and coagulation are not clearly defined. Thrombin is the main protease of the coagulation cascade and also participates in the host inflammatory response to tissue insult through activation of protease activated receptor-1 (PAR-1). PAR-1 is expressed in cells of the innate immune system. In this study we characterized the expression of PAR-1 on T cells from healthy controls. PAR-1 was expressed on CD4 and CD8 T cells with effector memory phenotype (23%±1.9 and 48%±3.5 respectively). Compared to healthy controls, patients with HIV infection had 1.6 times increased (p=0.0001) expression of PAR-1 on CD8 but not CD4 T cells. We hypothesized that thrombin could be involved in the recruitment of T cells to the place of tissue insult. Therefore, we imaged the effect of thrombin in individual cells over time using time-lapse microscopy. Thrombin was able to induce rapid kinesis after the addition of thrombin to human resting CD8 T cells in a PAR-1 dependent fashion. In addition, CD8 T cells from HIV infected patients were able to migrate in response to thrombin suggesting that during HIV infection CD8 T cells could respond to burst of thrombin leading to increased inflammation. This study provides new evidence of cross-talk between infection/coagulation adding a new player: T cells.