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不同的CD3/T细胞受体单克隆抗体诱导T淋巴细胞与内皮细胞黏附的能力各不相同。

Different CD3/T cell receptor monoclonal antibodies have distinct capacities to induce adhesion of T lymphocytes to endothelium.

作者信息

Buysmann S, Schellekens P T, Tax W J, ten Berge I J

机构信息

Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.

出版信息

J Lab Clin Med. 1997 Jul;130(1):91-101. doi: 10.1016/s0022-2143(97)90063-9.

DOI:10.1016/s0022-2143(97)90063-9
PMID:9242371
Abstract

Murine CD3/T cell receptor (TCR) monoclonal antibodies (mAbs) induce immediate peripheral lymphocytopenias of different degree and duration. Lymphocytopenia is of short duration after the administration of immunoglobulin A CD3 mAb, but it persists much longer after the administration of immunoglobulin G2a CD3 mAb. Peripheral lymphocytopenia after the administration of WT31, a murine immunoglobulin G1 TCR mAb, appears to be dependent on the polymorphism of Fc(gamma)RIIa. In high responders, lymphocytopenia is comparable to that observed after immunoglobulin G2a CD3 mAb; in low responders, no lymphocytopenia occurs. In vitro, both immunoglobulin A and immunoglobulin G2a CD3 mAbs induce immediate activation of CD11a/CD18, with concomitant up-regulation of CD11b/CD18 on T cells, each of which is shown to be involved in the concurrent adhesion of T cells to endothelium. WT31 induces an immediate activation of CD11a/CD18 as well as T cell adhesion to endothelium in Fc(gamma)RIIa high responders only, interestingly without changes in the level of expression of CD11b/CD18. We conclude that the immediate occurrence of peripheral lymphocytopenia after the administration of CD3/TCR mAb is mediated by changes in the level of expression or avidity (or both) of adhesion molecules on T cells, whereas the persistence of this lymphocytopenia depends on the isotype of the CD3/TCR mAb and on the presence of suitable Fc receptors.

摘要

小鼠CD3/T细胞受体(TCR)单克隆抗体(mAb)可诱导不同程度和持续时间的即刻外周淋巴细胞减少。给予免疫球蛋白A CD3 mAb后淋巴细胞减少持续时间较短,但给予免疫球蛋白G2a CD3 mAb后持续时间长得多。给予小鼠免疫球蛋白G1 TCR mAb WT31后的外周淋巴细胞减少似乎取决于Fc(γ)RIIa的多态性。在高反应者中,淋巴细胞减少与给予免疫球蛋白G2a CD3 mAb后观察到的情况相当;在低反应者中,不发生淋巴细胞减少。在体外,免疫球蛋白A和免疫球蛋白G2a CD3 mAb均可诱导CD11a/CD18即刻激活,同时T细胞上的CD11b/CD18上调,其中每一种均显示参与T细胞与内皮细胞的同时黏附。WT31仅在Fc(γ)RIIa高反应者中诱导CD11a/CD18即刻激活以及T细胞与内皮细胞黏附,有趣的是CD11b/CD18的表达水平没有变化。我们得出结论,给予CD3/TCR mAb后外周淋巴细胞减少的即刻发生是由T细胞上黏附分子表达水平或亲和力(或两者)的变化介导的,而这种淋巴细胞减少的持续时间取决于CD3/TCR mAb的同种型以及合适Fc受体的存在。

相似文献

1
Different CD3/T cell receptor monoclonal antibodies have distinct capacities to induce adhesion of T lymphocytes to endothelium.不同的CD3/T细胞受体单克隆抗体诱导T淋巴细胞与内皮细胞黏附的能力各不相同。
J Lab Clin Med. 1997 Jul;130(1):91-101. doi: 10.1016/s0022-2143(97)90063-9.
2
Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3.外周血淋巴细胞上黏附分子的激活和表达增加是注射OKT3后即刻淋巴细胞减少的一种机制。
Blood. 1996 Jan 1;87(1):404-11.
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Role of polymorphic Fc receptor Fc gammaRIIa in cytokine release and adverse effects of murine IgG1 anti-CD3/T cell receptor antibody (WT31).多态性Fc受体FcγRIIa在细胞因子释放及鼠源IgG1抗CD3/T细胞受体抗体(WT31)不良反应中的作用
Transplantation. 1997 Jan 15;63(1):106-12. doi: 10.1097/00007890-199701150-00020.
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Cultured human thymocytes lacking CD2 and CD11a/CD18 antigens are functional and adhere to endothelial cells via CD56 or CDw49d molecules.缺乏CD2和CD11a/CD18抗原的培养人胸腺细胞具有功能,并通过CD56或CDw49d分子黏附于内皮细胞。
Cell Immunol. 1992 Apr;140(2):319-30. doi: 10.1016/0008-8749(92)90199-y.
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A monoclonal antibody specific for a common determinant of the human T cell receptor gamma/delta directly activates CD3+WT31- lymphocytes to express their functional program(s).一种针对人T细胞受体γ/δ共同决定簇的单克隆抗体可直接激活CD3+WT31-淋巴细胞,使其表达其功能程序。
J Exp Med. 1988 Jul 1;168(1):1-11. doi: 10.1084/jem.168.1.1.
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Chimeric scFv/gamma receptor-mediated T-cell lysis of tumor cells is coregulated by adhesion and accessory molecules.嵌合单链抗体片段/γ受体介导的肿瘤细胞T细胞裂解受黏附分子和辅助分子共同调节。
Int J Cancer. 1998 Jul 17;77(2):181-7. doi: 10.1002/(sici)1097-0215(19980717)77:2<181::aid-ijc2>3.0.co;2-m.
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Monoclonal antibodies which react with the T cell receptor gamma/delta recognize different subsets of CD3+WT31- T lymphocytes.与T细胞受体γ/δ发生反应的单克隆抗体可识别CD3+WT31- T淋巴细胞的不同亚群。
Eur J Immunol. 1989 Jan;19(1):57-61. doi: 10.1002/eji.1830190110.
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Differential activation through the TCR-CD3 complex affects the requirement for costimulation of human T cells.通过TCR-CD3复合物的差异激活会影响人类T细胞共刺激的需求。
Hum Immunol. 1995 Jun;43(2):136-48. doi: 10.1016/0198-8859(94)00160-r.
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Participation of CD11a-c/CD18, CD2 and RGD-binding receptors in endogenous and interleukin-2-stimulated NK activity of CD3-negative large granular lymphocytes.CD11a-c/CD18、CD2和RGD结合受体在CD3阴性大颗粒淋巴细胞的内源性及白细胞介素-2刺激的自然杀伤活性中的作用。
Int J Cancer. 1990 Dec 15;46(6):1035-40. doi: 10.1002/ijc.2910460615.
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Interaction of human monocyte Fc gamma receptors with rat IgG2b. A new indicator for the Fc gamma RIIa (R-H131) polymorphism.人单核细胞Fcγ受体与大鼠IgG2b的相互作用。FcγRIIa(R-H131)多态性的新指标。
J Immunol. 1995 Feb 15;154(4):1852-60.

引用本文的文献

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Non FcR-binding murine antihuman CD3 monoclonal antibody is capable of productive TCR signalling and induces proliferation in the presence of costimulation.非FcR结合型鼠抗人CD3单克隆抗体能够产生有效的TCR信号,并在共刺激存在的情况下诱导增殖。
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