Human T lymphocyte activation by monoclonal antibodies; OKT3, but not UCHT1, triggers mitogenesis via an interleukin 2-dependent mechanism.
Human T lymphocyte activation by monoclonal antibodies; OKT3, but not UCHT1, triggers mitogenesis via an interleukin 2-dependent mechanism.
复制标题
单克隆抗体激活人T淋巴细胞；
作者：
J. V. Van Wauwe;J. Goossens;P. Beverley
OKT 3和UCHT 1单克隆抗体识别相同的人T细胞表面抗原，诱导T淋巴细胞增殖。在这份报告中，我们比较了这些抗体在人外周血单核细胞（PBMC）培养物中触发DNA合成的机制。尽管来自所有受试供体的PBMC均为OKT 3诱导的有丝分裂原，但40名供体中仅25名的细胞对UCHT 1有反应。UCHT1治疗应答者的PBMC，而非应答者的PBMC，导致T细胞表达与抗Tac单克隆抗体反应的膜结合位点，该单克隆抗体指定人白细胞介素2（IL 2）受体。来自无反应者的UCHT 1诱导的PBMC上清液（但出乎意料的是，也来自反应者）不含可测量的IL 2活性。与这一发现一致，抗Tac单克隆抗体未能抑制UCHT1触发的[3H]胸苷掺入来自应答供体的PBMC中。相反，OKT 3处理所有供体的PBMC导致IL 2受体的出现和大量IL 2的产生，并且所得的DNA合成可被抗Tac抗体所抑制。这些数据表明，具有相同T细胞结构的OKT 3和UCHT 1单克隆抗体的相互作用导致通过两种不同机制诱导增殖：一种依赖于IL 2（OKT 3）的可用性，另一种独立于该淋巴因子（UCHT 1）的产生和加工。PBMC对UCHT 1的无反应性因此可能与IL 2合成或IL 2受体展示功能障碍无关。
OKT3 and UCHT1 monoclonal antibodies, which recognize the same human T cell surface antigen, induce proliferation in T lymphocytes. In this report, we compared the mechanism by which these antibodies trigger DNA synthesis in human peripheral blood mononuclear cell (PBMC) cultures. Whereas PBMC from all donors tested were mitogenically inducible by OKT3, cells from only 25 of 40 donors were responsive to UCHT1 . UCHT1 treatment of PBMC from responders, but not from nonresponders, resulted in the expression by T cells of membrane binding sites reactive with anti-Tac monoclonal antibody, which specifies the human interleukin 2 (IL 2) receptor. UCHT1 -induced PBMC supernatants from nonresponders, but unexpectedly, also from responders, contained no measurable IL 2 activity. In keeping with this finding, anti-Tac monoclonal antibody failed to suppress UCHT1 -triggered [3H]thymidine incorporation into PBMC from responsive donors. By contrast, OKT3 treatment of PBMC from all donors led to the emergence of IL 2 receptors, and substantial IL 2 production, and the resultant DNA synthesis was inhibitable by anti-Tac antibody. These data indicate that the interaction of OKT3 and UCHT1 monoclonal antibodies with the same T cell structure leads to the induction of proliferation via two different mechanisms: one dependent on the availability of IL 2 (OKT3) and one independent on the production and processing of this lymphokine ( UCHT1 ). PBMC unresponsiveness to UCHT1 could therefore not be related to a dysfunction in IL 2 synthesis or IL 2 receptor display.