ARTERIAL AND VENULAR ENDOTHELIAL-CELL COSTIMULATION OF CYTOKINE SECRETION BY HUMAN T-CELL CLONES

Vascular endothelial cell (EC) costimulation of cytokine secretion by T lymphocytes may be important in inflammation and allograft rejection , Venous and arterial iliac endothelial cells (VIEC, AIEC) both costim ulate interleukin-2 (IL-2) production by peripheral blood lymphocytes (PBL) or T cell clones stimulated with phytohemagglutainin (PHA), Inte rferon-gamma (IFN-gamma) production is costimulated in a subset of clo nes but IL-4 is not. Suprisingly two T cell clones were reciprocally b etter costimulated by VIEC or AIEC. EC activation by pretreatment with tumor necrosis factor alpha (TNF-alpha) does not increase T cell cost imulation despite large increases in EC cell adhesion molecule express ion. Neither VIEC nor AIEC express CTLA4-binding molecules and costimu lation is blocked by cyclosporin A, suggesting that CD28 if not involv ed in EC costimulation of T cells. These data suggest that adult vascu lar EC costimulate production of IL-2 and IFN-gamma but not IL-4 by ma ture T cells, that EC costimulation is not increased in inflamed tissu es, and that different EC optimally costimulate particular T cells. Th ese findings have implications for the nature of the costimulatory sig nal(s) provided by EC and may be important in understanding vasculitis or atherosclerosis.