Inhibition of specific cell-mediated cytotoxicity by monoclonal antibodies to human T cell antigens.
Inhibition of specific cell-mediated cytotoxicity by monoclonal antibodies to human T cell antigens.
复制标题
通过针对人 T 细胞抗原的单克隆抗体抑制特定细胞介导的细胞毒性。
DOI：
10.1073/pnas.78.7.4500
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发表时间：
1981
影响因子：
11.1
通讯作者：
R. Good
中科院分区：
文献类型：
--
作者：
C. Platsoucas;R. Good
人类T淋巴细胞亚群最近已被定义为单克隆抗体，识别细胞表面抗原选择性表达的功能不同的T细胞亚群。大多数（约90%）外周血绵羊红细胞玫瑰花结形成细胞携带OKT 3抗原。辅助细胞是OKT 4（+），而细胞毒性/抑制细胞是OKT 5（+）和OKT 8（+）。我们研究了识别T细胞抗原的几种单克隆抗体对T细胞的某些增殖反应和混合淋巴细胞培养（MLC）中产生的特异性T细胞介导的细胞毒性的效应期的影响。在没有添加补体的情况下，（i）OKT 3和OKT 4单克隆抗体抑制对植物血凝素（PHA）的增殖反应，（ii）OKT 3单克隆抗体抑制MLC中对同种异体细胞的增殖反应，和（iii）OKT 3单克隆抗体显著且规律地抑制特异性T细胞介导的针对同种异体靶的细胞毒性的效应期（P < 0.001），呈浓度依赖性。OKT 5和OKT 8单克隆抗体，再次在不存在补体的情况下，适度抑制特异性细胞介导的细胞毒性。仅在某些实验中观察到这种抑制。在继发性反应中也观察到这些抗体对特异性细胞毒性的抑制。相反，同样在不存在添加的补体的情况下，这些抗体均不影响MLC中产生的针对K562靶标的非特异性细胞毒性。在不存在添加的补体的情况下，OKT 4抗体对特异性或非特异性细胞毒性均无影响。此外，用OKT 3或OKT 8抗体和补体处理完全消除了特异性T细胞介导的细胞毒性，但对针对K562细胞的天然补体样细胞毒性没有影响。用OKT 4抗体和补体治疗没有效果。这些结果表明：（i）细胞毒性T淋巴细胞上存在的T5/T8和T3抗原可能直接或间接参与抗原识别步骤或T细胞介导的淋巴细胞溶解的溶解机制;（ii）MLC中产生的针对K562靶标的非特异性细胞毒性由表型不同于介导特异性细胞毒性的细胞介导。
Human T lymphocyte subpopulations recently have been defined by monoclonal antibodies that recognize cell-surface antigens selectively expressed on functionally distinct T cell subsets. The majority (approximately 90%) of the peripheral blood sheep erythrocyte-rosette-forming cells carry the OKT3 antigen. Helper cells are OKT4(+), whereas cytotoxic/suppressor cells are OKT5(+) and OKT8(+). We investigated the effect of several monoclonal antibodies recognizing T cell antigens on certain proliferative responses of T cells and on the effector phase of the specific T cell-mediated cytotoxicity generated in mixed lymphocyte culture (MLC). In the absence of added complement, (i) OKT3 and OKT4 monoclonal antibodies inhibited the proliferative response to phytohemagglutinin (PHA), (ii) OKT3 monoclonal antibody inhibited the proliferative response to allogeneic cells in MLC, and (iii) OKT3 monoclonal antibody significantly and regularly inhibited the effector phase of the specific T cell-mediated cytotoxicity against allogeneic targets (P < 0.001) in a concentration-dependent manner. The OKT5 and OKT8 monoclonal antibodies, again in the absence of complement, inhibited moderately the specific cell-mediated cytotoxicity. This inhibition was observed in some experiments only. Inhibition of the specific cytotoxicity by these antibodies also was observed in secondary responses. In contrast, again in the absence of added complement, none of these antibodies had an effect on the nonspecific cytotoxicity generated in MLC against the K562 targets. The OKT4 antibody in the absence of added complement had no effect on either the specific or nonspecific cytotoxicity. Furthermore, treatment with OKT3 or OKT8 antibody and complement completely abrogated the specific T cell-mediated cytotoxicity but had no effect on the natural killer-like cytotoxicity against the K562 cells. Treatment with the OKT4 antibody and complement had no effect. These results suggest that (i) the T5/T8 and T3 antigens, present on cytotoxic T lymphocytes, may be involved directly or indirectly in the antigen recognition step(s) or the lytic mechanism of T cell-mediated lympholysis; and (ii) nonspecific cytotoxicity against the K562 targets generated in MLC is mediated by cells phenotypically different than those that mediate specific cytotoxicity.