Tumor necrosis factor-alpha (TNF-alpha) induces a reversible, time- and dose-dependent adhesion of progenitor T cells to endothelial cells.
Recent in vivo studies suggest that tumor necrosis factor-alpha (TNF-alpha) 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 TNF-alpha 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-alpha 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-alpha concentrations 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 larger than that of untreated monolayers. A slow decrease in adherence, down 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 continued stimulation caused the adherence to return to pre-stimulation levels within 24-30 hr. Adhesion of FTF1 cells to TNF-alpha treated 1F8 cells was almost completely blocked by a monoclonal antibody against murine CD49d (very late antigen-4) expressed on FTF1 cells. TNF-alpha-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-alpha could modulate the dynamics of adhesion of progenitor T cells to the thymic endothelium.
Aparicio
C L
CL
Department of Chemical and Biochemical Engineering, Rutgers University, Piscataway, NJ 08855, USA.
Berthiaume
F
F
Chang
C C
CC
Yarmush
M L
ML
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001667:Binding, Competitive / Q000276:immunology; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007700:Kinetics; D051379:Mice; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha