Regulation of human T lymphocyte mitogenesis by antibodies to CD3.
Regulation of human T lymphocyte mitogenesis by antibodies to CD3.
复制标题
CD3 抗体调节人 T 淋巴细胞有丝分裂。
作者：
L. Davis;R. Vida;P. Lipsky
在人外周血T细胞培养物中检测抗CD 3抗体（抗CD 3）的抑制和促有丝分裂作用。静息T细胞需要辅助细胞（AC）或佛波醇肉豆蔻酸酯乙酸酯（PMA）的存在以被可溶性抗-CD 3（OKT 3和64.1）刺激。通过IL 2受体表达、IL 2产生、细胞周期分析或可检测的DNA合成测定，抗CD 3不能诱导AC耗尽的T细胞活化。虽然T细胞对PHA的反应也需要AC，但产生反应所需的数量要少得多。在部分AC去除的培养物中，抗CD 3抑制PHA刺激的T细胞IL 2产生、IL 2受体表达和增殖。此外，抗-CD 3能够抑制PHA反应时，添加到培养物迟至24至42小时后开始的96小时孵育。增加PHA浓度可降低抗CD 3抗体对PHA刺激的T细胞增殖的抑制作用，而IL 2的产生仍然受到抑制。与琼脂糖凝胶珠连接的抗CD 3有效地抑制PHA刺激的T细胞DNA合成，表明抑制PHA应答不需要CD 3分子的内化。虽然抑制IL 2的产生是抗CD 3在PHA刺激的培养物中的主要作用，但它不是唯一的明显抑制作用，因为外源性IL 2的加入不能完全阻止抑制。完整的AC而不是IL 1也减少了抗CD 3介导的PHA反应性抑制，而IL 2和AC的加入在很大程度上阻止了抑制。因此，在缺乏足够AC信号的情况下，抗CD 3对有丝分裂原诱导的T细胞活化产生许多不同的抑制作用。这些结果表明，CD 3分子复合物可能通过多种机制参与T细胞受体后在调节T细胞反应性中发挥作用，其中一些机制涉及抑制IL 2的产生。
The inhibitory and mitogenic effects of anti-CD3 antibodies (anti-CD3) were examined in cultures of human peripheral blood T cells. Resting T cells required the presence of accessory cells (AC) or phorbol myristate acetate (PMA) to be stimulated by soluble anti-CD3 (OKT3 and 64.1). Anti-CD3 was unable to induce activation of AC-depleted T cells as determined by IL 2 receptor expression, IL 2 production, cell cycle analysis, or detectable DNA synthesis. Although T cell responses to PHA also required AC, far fewer were necessary to generate responses. Anti-CD3 inhibited PHA-stimulated T cell IL 2 production, IL 2 receptor expression and proliferation in partially AC-depleted cultures. Moreover, anti-CD3 was able to inhibit PHA responses when added to culture as late as 24 to 42 hr after the initiation of a 96-hr incubation. Increasing concentrations of PHA reduced the inhibitory effect of anti-CD3 on PHA-stimulated T cell proliferation, whereas IL 2 production remained suppressed. Anti-CD3 linked to Sepharose beads effectively inhibited PHA-stimulated T cell DNA synthesis, indicating that internalization of the CD3 molecule was not required for inhibition of PHA responses. Although inhibition of IL 2 production was a major effect of anti-CD3 in PHA-stimulated cultures, it was not the only apparent inhibitory effect because the addition of exogenous IL 2 could not prevent inhibition completely. Intact AC but not IL 1 also reduced anti-CD3-mediated inhibition of PHA responsiveness, whereas the addition of both IL 2 and AC largely prevented inhibition. Thus, anti-CD3 in the absence of adequate AC signals exerted a number of distinct inhibitory effects on mitogen-induced T cell activation. These results suggest that the CD3 molecular complex may play a role in regulating T cell responsiveness after engagement of the T cell receptor by a number of mechanisms, some of which involve inhibition of IL 2 production.