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抗人T细胞抗原单克隆抗体对特异性细胞介导细胞毒性的抑制作用。

Inhibition of specific cell-mediated cytotoxicity by monoclonal antibodies to human T cell antigens.

作者信息

Platsoucas C D, Good R A

出版信息

Proc Natl Acad Sci U S A. 1981 Jul;78(7):4500-4. doi: 10.1073/pnas.78.7.4500.

DOI:10.1073/pnas.78.7.4500
PMID:6974866
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC319819/
Abstract

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.

摘要

最近,人类T淋巴细胞亚群已通过单克隆抗体得以界定,这些抗体可识别在功能各异的T细胞亚群上选择性表达的细胞表面抗原。外周血中大多数(约90%)能形成绵羊红细胞玫瑰花结的细胞携带OKT3抗原。辅助性细胞为OKT4(+),而细胞毒性/抑制性细胞为OKT5(+)和OKT8(+)。我们研究了几种识别T细胞抗原的单克隆抗体对T细胞某些增殖反应以及对混合淋巴细胞培养(MLC)中产生的特异性T细胞介导的细胞毒性效应阶段的影响。在不添加补体的情况下,(i)OKT3和OKT4单克隆抗体抑制对植物血凝素(PHA)的增殖反应,(ii)OKT3单克隆抗体抑制MLC中对同种异体细胞的增殖反应,并且(iii)OKT3单克隆抗体以浓度依赖方式显著且规律性地抑制针对同种异体靶标的特异性T细胞介导的细胞毒性效应阶段(P < 0.001)。同样在不添加补体的情况下,OKT5和OKT8单克隆抗体适度抑制特异性细胞介导的细胞毒性。仅在一些实验中观察到这种抑制作用。在二次反应中也观察到这些抗体对特异性细胞毒性的抑制作用。相比之下,同样在不添加补体的情况下,这些抗体均未对MLC中针对K562靶标的非特异性细胞毒性产生影响。在不添加补体的情况下,OKT4抗体对特异性或非特异性细胞毒性均无影响。此外,用OKT3或OKT8抗体及补体处理可完全消除特异性T细胞介导的细胞毒性,但对针对K562细胞的自然杀伤样细胞毒性无影响。用OKT4抗体及补体处理则无作用。这些结果表明,(i)存在于细胞毒性T淋巴细胞上的T5/T8和T3抗原可能直接或间接参与T细胞介导的淋巴细胞溶解的抗原识别步骤或裂解机制;并且(ii)MLC中针对K562靶标的非特异性细胞毒性是由表型不同于介导特异性细胞毒性的细胞介导的。

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The differentiation and function of human T lymphocytes.人类T淋巴细胞的分化与功能。
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Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to TH2 antigen.人类中依赖胸腺的膜抗原:抗TH2抗原单克隆抗体对细胞介导的淋巴细胞溶解的抑制作用
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A monoclonal antibody reactive with the human cytotoxic/suppressor T cell subset previously defined by a heteroantiserum termed TH2.一种单克隆抗体,可与人细胞毒性/抑制性T细胞亚群发生反应,该亚群先前由一种名为TH2的异种抗血清所定义。
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Defective spontaneous and antibody-dependent cytotoxicity mediated by E-rosette-positive and E-rosette-negative cells in untreated patients with chronic lymphocytic leukemia: augmentation by in vitro treatment with interferon.未经治疗的慢性淋巴细胞白血病患者中,E花环阳性和E花环阴性细胞介导的自发性及抗体依赖性细胞毒性存在缺陷:体外干扰素治疗可增强其细胞毒性。
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