Blockade of the interleukin-2 receptor by anti-Tac antibody: inhibition of human lymphocyte activation.
Blockade of the interleukin-2 receptor by anti-Tac antibody: inhibition of human lymphocyte activation.
复制标题
抗 Tac 抗体阻断白细胞介素 2 受体：抑制人淋巴细胞活化。
作者：
J. Depper;W. Leonard;R. Robb;T. Waldmann;W. Greene
我们之前已经证明单克隆抗tac抗体抑制白细胞介素-2 （IL-2）依赖性人连续T细胞系的增殖。此外，我们已经证明anti-Tac特异性阻断了超过95%的放射性标记II-2与连续T细胞系的结合。鉴于这些数据，我们认为抗tac抗体可能结合并阻断人T细胞受体IL-2。我们现在报道了抗tac对人外周血T淋巴细胞活化的影响。我们发现抗tac: 1)阻断可溶性抗原（80-90%）、自体抗原（90%）和同种抗原（75-90%）诱导的T细胞增殖；2)部分抑制有丝分裂凝集素诱导的T细胞增殖，包括刀豆蛋白A（50-88%）、美洲商陆有丝分裂原（40-87%）和植物血凝素（20-80%）；3)消除（大于95%）同种异体细胞共培养中溶细胞T淋巴细胞的产生，但不抑制一旦形成的溶细胞T淋巴细胞的杀伤作用；4)和抑制T细胞依赖性商陆有丝分裂原激活的B细胞免疫球蛋白的产生（78-95%）。我们进一步证明，抗tac对增殖的抑制不是继发于IL-2产生的减少。最后，在抗原诱导的T细胞增殖试验中，我们证明了高纯度IL-2的加入逆转了抗tac的抑制作用。这些数据与anti-Tac识别人类IL-2受体的假设是一致的，并说明了这种抗体可以用来调节人类免疫反应的方法。
We have previously shown that monoclonal anti-Tac antibody inhibits the proliferation of interleukin-2 (IL-2) dependent human continuous T cell lines. Further, we have shown that anti-Tac specifically blocks greater than 95% of the binding of radiolabeled II-2 to a continuous T cell line. In view of these data, we suggested that anti-Tac antibody may bind to and block the human T cell receptor for IL-2. We now report the effects of anti-Tac on the activation of human peripheral blood T lymphocytes. We find that anti-Tac: 1) blocks T cell proliferation induced by soluble antigens (80-90%), autologous antigens (90%) and alloantigens (75-90%); 2) partially inhibits T cell proliferation induced by mitogenic lectins, including Concanavalin A (50-88%), pokeweed mitogen (40-87%), and phytohemagglutinin (20-80%); 3) abrogates (greater than 95%) the generation of cytolytic T lymphocytes in allogeneic cell cocultures, but does not inhibit killing by cytolytic T lymphocytes once formed; 4) and inhibits T cell dependent pokeweed mitogen activated B cell immunoglobulin production (78-95%). We further demonstrate that anti-Tac inhibition of proliferation is not secondary to diminished production of IL-2. Finally, in antigen induced T cell proliferative assays, we demonstrate that the addition of highly purified IL-2 reverses the inhibitory effects of anti-Tac. These data are consistent with the hypothesis that anti-Tac recognizes the human IL-2 receptor and illustrate ways in which this antibody can be used to modulate the human immune response.