Tumor necrosis factor-alpha (TNF-α) induces a reversible, time- and dose-dependent adhesion of progenitor T cells to endothelial cells

Recent in vivo studies suggest that tumor necrosis factor-α (TNF-α) 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 found that TNFα increases the adhesion of a murine progenitor T cell line (FTF1) to a bovine aortic endothelial cell line (1F8), human umbilical vein endothelial (HUVE) cells, and a murine arterial endothelial (MAE) cell line. TNF-α treatment of the 1F8 cells resulted in a time- and dose-dependent increase in the adherence of FTF1 cells. Adherence increased during the first 6 hr of treatment with TNF-α concentrations ranging from 10^-11 to 10^-9 M. Maximal adherence (6 hr treatment with 10^-10 M of TNF-α) was approximately 4.5-fold larger than that of untreated monolayers. A slow decrease in adherence, down to approximately 2-fold at 48 hr, was observed beyond 12 hr o TNF-α treatment; in contrast, removal of TNF-α after 6 hr of continued stimulation caused the adherence to return to pre-stimulation levels within 24-30 hr. Adhesion of FTF1 cells to TNF-α-treated 1F8 cells was almost completely blocked by a monoclonal antibody against murine CD49d (very late antigen-4) expressed on FTF1 cells. TNF-α-induced adhesion of FTF1 cells to MAE cells was also blocked by monoclonal antibodies against murine CD49d and CD106 (vascular cell adhesion molecule-1). These results support the notion that local secretion of TNF-α could modulate the dynamics of adhesion of progenitor T cells to the thymic endothelium.