Enhanced Effector Function of CD8 super(+) T Cells From Healthy Controls and HIV-Infected Patients Occurs Through Thrombin Activation of Protease-Activated Receptor 1

• Published in: The Journal of infectious diseases Vol. 207; no. 4; pp. 638 - 650
• Main Authors: Hurley, Amanda, Smith, Mindy, Karpova, Tatiana, Hasley, Rebecca B, Belkina, Natalya, Shaw, Stephen, Balenga, Nariman, Druey, Kirk M, Nickel, Erin, Packard, Beverly
• Format: Journal Article
• Language: English
• Published: 15-02-2013
• Subjects: Human immunodeficiency virus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis730

Disruption of vascular integrity by trauma and other tissue insults leads to inflammation and activation of the coagulation cascade. The serine protease thrombin links these 2 processes. The proinflammatory function of thrombin is mediated by activation of protease-activated receptor 1 (PAR-1). We found that peripheral blood effector memory CD4 super(+) and CD8 super(+) T lymphocytes expressed PAR-1 and that expression was increased in CD8 super(+) T cells from human immunodeficiency virus (HIV)-infected patients. Thrombin enhanced cytokine secretion in CD8 super(+) T cells from healthy controls and HIV-infected patients. In addition, thrombin induced chemokinesis, but not chemotaxis, of CD8 super(+) T cells, which led to structural changes, including cell polarization and formation of a structure rich in F-actin and phosphorylated ezrin-radexin-moesin proteins. These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T-cell motility and production of proinflammatory cytokines.