Enhanced effector function of CD8(+) T cells from healthy controls and HIV-infected patients occurs through thrombin activation of protease-activated receptor 1

J Infect Dis. 2013 Feb 15;207(4):638-50. doi: 10.1093/infdis/jis730. Epub 2012 Nov 29.

Abstract

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(+) and CD8(+) T lymphocytes expressed PAR-1 and that expression was increased in CD8(+) T cells from human immunodeficiency virus (HIV)-infected patients. Thrombin enhanced cytokine secretion in CD8(+) T cells from healthy controls and HIV-infected patients. In addition, thrombin induced chemokinesis, but not chemotaxis, of CD8(+) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Blood Coagulation / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cytokines / metabolism
  • Female
  • HIV Infections / blood*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / pathogenicity*
  • Humans
  • Immunologic Memory
  • Inflammation / immunology
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • Receptor, PAR-1 / metabolism*
  • Thrombin / immunology*
  • Thrombin / metabolism

Substances

  • Cytokines
  • Receptor, PAR-1
  • Thrombin