Dumont F J, Palfree R G, Fisher P A
Dept. of Immunology Research, Merck, Sharp and Dohme Research Laboratories, Rahway, NJ 07065.
Immunology. 1988 Jun;64(2):267-71.
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.
已证实，在对T细胞进行促有丝分裂刺激后，T细胞活化蛋白（TAP）糖蛋白的表面表达会增加。最近，我们发现，在静息T细胞中，外源性干扰素-γ（IFN-γ）也会增加TAP的表达。由于已知T细胞在活化后会分泌IFN-γ，我们推测活化T细胞中TAP的增强可能反映了内源性IFN-γ的自分泌作用。我们使用一种有效的中和抗IFN-γ单克隆抗体（H-22.10）来检验这种可能性。发现刀豆蛋白A（Con A）刺激的T细胞的上清液可诱导静息T细胞中TAP增强，且这种作用被抗IFN-γ单克隆抗体阻断。用Con A或离子霉素加佛波醇肉豆蔻酸酯的组合刺激T细胞，会使TAP表达显著增加。发现在此类受刺激的T细胞培养开始时加入H-22.10单克隆抗体可阻止TAP增强，但不影响IL-2受体的出现或Pgp-1表达的增加。综上所述，这些数据表明IFN-γ是受刺激T细胞释放的主要TAP增强介质。因此，内源性产生的IFN-γ而非细胞活化本身，是刺激T细胞中TAP表达增加的原因。
