TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) INDUCES A REVERSIBLE, TIME-DEPENDENT AND DOSE-DEPENDENT ADHESION OF PROGENITOR T-CELLS TO ENDOTHELIAL-CELLS

Recent in vivo studies suggest that tumor necrosis factor-alpha (TNF-a lpha) is involved in the development of the thymus. We postulated that this inflammatory mediator could regulate the influx of progenitor T cells into the thymus. Using an in vitro static adhesion system, we fo und that TNF-alpha increases the adhesion of a murine progenitor T cel l line (FTF1) to a bovine aortic endothelial cell line (1F8), human um bilical vein endothelial (HUVE) cells, and a murine arterial endotheli al (MAE) cell line. TNF-alpha treatment of the 1F8 cells resulted in a time- and dose-dependent increase in the adherence of FTF1 cells. Adh erence increased during the first 6 hr of treatment with TNF-alpha con centrations ranging from 10(-11) to 10(-9) M. Maximal adherence (6 hr treatment with 10(-10) M of TNF-alpha) was approximately 4.5-fold larg er than that of untreated monolayers. A slow decrease in adherence, do wn to approximately 2-fold at 48 hr, was observed beyond 12 hr of TNF- alpha treatment; in contrast, removal of TNF-alpha after 6 hr of conti nued stimulation caused the adherence to return to pre-stimulation lev els within 24-30 hr. Adhesion of FTF1 cells to TNF-alpha-treated 1F8 c ells was almost completely blocked by a monoclonal antibody against mu rine CD49d (very late antigen-4) expressed on FTF1 cells. TNF-alpha-in duced adhesion of FTF1 cells to MAE cells was also blocked by monoclon al antibodies against murine CD49d and CD106 (vascular cell adhesion m olecule-1). These results support the notion that local secretion of T NF-alpha could modulate the dynamics of adhesion of progenitor T cells to the thymic endothelium. Copyright (C) 1996 Elsevier Science Ltd.