T cell-mediated signaling to vascular endothelium: induction of cytokines, chemokines, and tissue factor.
Adhesion of leukocytes to the vascular endothelium is an early event in inflammation. Since cell-cell signaling may be an important stimulus for endothelial activation, we focused in this study on the role of contact-mediated activation by T lymphocytes of endothelial cells (EC). T lymphocytes were cultured with anti-CD3 monoclonal antibody or in the presence of a combination of TNF-alpha, interleukin (IL)-6, and IL-2, prior to fixation and coculture with human umbilical vein EC. Fixed, activated (anti-CD3- or cytokine-stimulated), but not unstimulated T cells, induced release of monocyte chemotactic protein-1, IL-8, and IL-6 by EC in a contact-dependent manner. Moreover, expression of tissue-factor antigen and activity was also significantly increased. Addition of anti-CD40 ligand antibody abolished T cell-induced activation of EC. Our data suggest that contact-mediated activation of EC by T cells, involving ligand:counter ligand interactions such as CD40:CD40 ligand, may represent a novel pathogenic mechanism of progression in inflammatory diseases such as atherosclerosis or rheumatoid arthritis.
Monaco
Claudia
C
Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology & Medicine, London, United Kingdom. c.monaco@ic.ac.uk
Andreakos
Evangelos
E
Young
Sylvia
S
Feldmann
Marc
M
Paleolog
Ewa
E
D023201:CD40 Ligand / Q000502:physiology; D002450:Cell Communication; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*; D013925:Thromboplastin / Q000096:biosynthesis*
D018925:Chemokines; D016207:Cytokines; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D023201:CD40 Ligand; D013925:Thromboplastin