The T-cell activating protein (TAP) is up-regulated by endogenous IFN-gamma in activated T cells.
The surface expression of the T-cell activating protein (TAP) glycoprotein has been shown to be increased following mitogenic stimulation of T cells. Recently, we found that TAP is also augmented by exogenous interferon-gamma (IFN-gamma) in resting T cells. Because T cells are known to secrete IFN-gamma upon activation, we postulated that TAP enhancement in activated T cells may reflect an autocrine action of endogenous IFN-gamma. This possibility was examined using a potent neutralizing anti-IFN-gamma mAb (H-22.10). Supernatants from Concanavalin A (Con A)-stimulated T cells were found to induce TAP enhancement in resting T cells, and this effect was blocked by the anti-IFN-gamma mAb. Stimulation of T cells with Con A or with the combination of ionomycin plus phorbol myristate acetate produced a marked increase of TAP expression. Addition of the H-22.10 mAb at the initiation of such stimulated T-cell cultures was found to prevent the augmentation of TAP but not to affect the emergence of IL-2 receptors or the increase of Pgp-1 expression. Taken together, these data demonstrate that IFN-gamma is the principal TAP-enhancing mediator released by stimulated T cells. Endogenously produced IFN-gamma, rather than cell activation per se, is thus responsible for the augmentation of TAP expression in stimulated T cells.
Dumont
F J
FJ
Dept. of Immunology Research, Merck, Sharp and Dohme Research Laboratories, Rahway, NJ 07065.
Palfree
R G
RG
Fisher
P A
PA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis*; D003208:Concanavalin A / Q000494:pharmacology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D003208:Concanavalin A; D007371:Interferon-gamma