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OKT3单克隆抗体抑制细胞毒性T淋巴细胞介导的细胞裂解。

OKT3 monoclonal antibody inhibits cytotoxic T lymphocyte mediated cell lysis.

作者信息

Chang T W, Gingras S P

出版信息

Int J Immunopharmacol. 1981;3(3):183-6. doi: 10.1016/0192-0561(81)90011-4.

DOI:10.1016/0192-0561(81)90011-4
PMID:6457003
Abstract

Human alloreactive cytotoxic T lymphocytes (CTLs) were generated in culture by stimulating peripheral blood lymphocytes against lymphocytes of unrelated donors. OKT3 monoclonal antibody, which reacts with all human peripheral T cells, inhibited more than 50% of the lysis of the allogeneic cells by the CTLs in the four-hour cytotoxicity assay at a concentration of 1 microgram ml-1. OKT4, which reacts with inducer/helper T cells, did not demonstrate this effect. OKT5 and OKT8, both of which react with cytotoxic/suppressor T cells, had a small but distinct inhibitory effect (about 20-30% maximally). OKT3 antibody is also known to induce mitogenesis of peripheral T cells, but this mitogenic effect is probably of itself not the cause of the inhibitory effect of OKT3 on CTLs. Human plasma abolished OKT3-induced mitogenesis of T cells but not OKT3-mediated inhibition of CTL activity. In addition, there exist conditions that allow both full mitogenesis and intact CTL activity, suggesting CTLs can maintain cytolytic activity under mitogenic conditions. The generation of CTLs in the 6-day mixed lymphocyte culture was also inhibited by OKT3. Several possible mechanisms for this effect are discussed.

摘要

通过用无关供体的淋巴细胞刺激外周血淋巴细胞,在培养中产生人同种异体反应性细胞毒性T淋巴细胞(CTL)。与所有人外周T细胞发生反应的OKT3单克隆抗体,在浓度为1微克/毫升时,在四小时细胞毒性试验中抑制了CTL对同种异体细胞的50%以上的裂解。与诱导/辅助性T细胞发生反应的OKT4没有显示出这种作用。与细胞毒性/抑制性T细胞发生反应的OKT5和OKT8有微小但明显的抑制作用(最大约20%-30%)。已知OKT3抗体也可诱导外周T细胞的有丝分裂,但这种有丝分裂作用本身可能不是OKT3对CTL抑制作用的原因。人血浆消除了OKT3诱导的T细胞有丝分裂,但没有消除OKT3介导的CTL活性抑制。此外,存在允许完全有丝分裂和完整CTL活性的条件,这表明CTL在有丝分裂条件下可维持细胞溶解活性。OKT3也抑制了6天混合淋巴细胞培养中CTL的产生。讨论了这种作用的几种可能机制。

相似文献

1
OKT3 monoclonal antibody inhibits cytotoxic T lymphocyte mediated cell lysis.OKT3单克隆抗体抑制细胞毒性T淋巴细胞介导的细胞裂解。
Int J Immunopharmacol. 1981;3(3):183-6. doi: 10.1016/0192-0561(81)90011-4.
2
Inhibition of specific cell-mediated cytotoxicity by monoclonal antibodies to human T cell antigens.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。
Proc Natl Acad Sci U S A. 1981 Jul;78(7):4500-4. doi: 10.1073/pnas.78.7.4500.
3
Does OKT3 monoclonal antibody react with an antigen-recognition structure on human T cells?OKT3单克隆抗体是否与人类T细胞上的抗原识别结构发生反应?
Proc Natl Acad Sci U S A. 1981 Mar;78(3):1805-8. doi: 10.1073/pnas.78.3.1805.
4
Cyclosporin-A and the OKT3 monoclonal antibody exert their respective inhibitory and mitogenic activity on T cells by interacting with the same receptors.环孢素A和OKT3单克隆抗体通过与相同受体相互作用,分别对T细胞发挥抑制和促有丝分裂活性。
J Clin Immunol. 1982 Jul;2(3 Suppl):15S-19S.
5
OKT3 induces suppressor cells for mixed lymphocyte and PHA mitogenic responses in human peripheral lymphocytes.OKT3可诱导人外周血淋巴细胞中混合淋巴细胞反应及PHA促有丝分裂反应的抑制性细胞。
Int J Immunopharmacol. 1981;3(3):187-92. doi: 10.1016/0192-0561(81)90012-6.
6
OKT3: a monoclonal anti-human T lymphocyte antibody with potent mitogenic properties.OKT3:一种具有强大促有丝分裂特性的单克隆抗人T淋巴细胞抗体。
J Immunol. 1980 Jun;124(6):2708-13.
7
Spontaneous human T-cell cytotoxicity against murine hybridomas expressing the OKT3 monoclonal antibody: comparison with natural killer cell activity.人自发T细胞对表达OKT3单克隆抗体的鼠杂交瘤细胞的细胞毒性:与自然杀伤细胞活性的比较。
Cell Immunol. 1987 Sep;108(2):313-22. doi: 10.1016/0008-8749(87)90215-2.
8
In vitro mixed skin cell lymphocyte culture reaction (MSLR) in man: analysis of the epidermal cell and T cell subpopulations.人体外混合皮肤细胞淋巴细胞培养反应(MSLR):表皮细胞和T细胞亚群分析
Clin Exp Immunol. 1982 Nov;50(2):426-33.
9
OKT8 antibody inhibits OKT3-induced IL 2 production and proliferation in OKT8+ cells.OKT8抗体可抑制OKT3诱导的OKT8 +细胞中白细胞介素2的产生和增殖。
J Immunol. 1983 Nov;131(5):2356-61.
10
Lysis of fresh solid tumor targets in the presence of Con A is mediated primarily by Leu 7+ peripheral blood T lymphocytes: blocking by the anti-CD3 monoclonal antibody and comparison with recombinant interleukin 2-induced lysis by natural killer cells.在伴刀豆球蛋白A存在的情况下,新鲜实体瘤靶标的裂解主要由Leu 7⁺外周血T淋巴细胞介导:抗CD3单克隆抗体的阻断作用以及与重组白细胞介素2诱导的自然杀伤细胞裂解作用的比较。
Cell Immunol. 1987 Sep;108(2):283-96. doi: 10.1016/0008-8749(87)90213-9.

引用本文的文献

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Use of OKT3 with cyclosporin and steroids for reversal of acute kidney and liver allograft rejection.使用OKT3联合环孢素和类固醇来逆转急性肾和肝移植排斥反应。
Nephron. 1987;46 Suppl 1(Suppl 1):19-33. doi: 10.1159/000184431.
2
Studies on cytotoxicity generated in human mixed lymphocyte culture. IV. Interleukin 2 alone or from mixed lymphocyte culture yields natural killer-like cytotoxic cells distinct from allospecific cytotoxic T lymphocytes.人类混合淋巴细胞培养中产生的细胞毒性研究。IV. 单独的白细胞介素2或混合淋巴细胞培养产生的白细胞介素2可产生不同于同种特异性细胞毒性T淋巴细胞的自然杀伤样细胞毒性细胞。
Cancer Immunol Immunother. 1988;27(3):255-60. doi: 10.1007/BF00205448.
3
Muromonab CD3. A review of its pharmacology and therapeutic potential.
莫罗单抗-CD3。其药理学与治疗潜力综述。
Drugs. 1989 Jun;37(6):871-99. doi: 10.2165/00003495-198937060-00004.
4
The role of OKT3 in clinical transplantation.OKT3在临床移植中的作用。
Pediatr Nephrol. 1991 Jan;5(1):130-6. doi: 10.1007/BF00852870.