Increased activated platelet-T cell conjugates in patients with HIV infection: relationship between coagulation/inflammation and T cells. (VIR10P.1171)

Abstract

Abstract While antiretroviral therapies can successfully suppress HIV replication, there remains evidence of persistent immune activation, which is correlated with increased risks of all-cause mortality. Patients with elevated biomarkers of coagulation/inflammation such as IL-6, sCD14 and D-dimer (a fibrin bioproduct) are at an increased risk to develop non-AIDS defining illnesses such as cardiovascular disease. The interaction between the coagulation system and the immune system is critical for host defense; however, in HIV infection, the mechanisms underlying the ongoing activation of these pathways remains poorly understood. We hypothesized that interaction between platelets and T cells may play a role. We found that platelets from healthy controls and HIV infected patients bind to CD4 and CD8 T cells, preferentially to those with memory phenotypes. HIV infected patients showed a higher proportion of activated platelet (CD42b+CD62P+)-T cell conjugates and significantly correlated to the D-dimer levels. In vitro thrombin stimulation of PBMCs enhanced formation of platelet-T cell conjugates mediated in part by CD62P released by platelets. These data suggest that platelets can promote trafficking of T cells into injured tissues by upregulation of CD62P leading to enhanced rolling of leukocytes along vascular endothelium. In HIV infected patients, recruitment of T cells by this mechanism may promote a state of inflammation/coagulation and contribute to the pathology of the disease.