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单克隆抗体免疫抑制。一种确定有效血清疗法规则的模型。

Immunosuppression with monoclonal antibodies. A model to determine the rules for effective serotherapy.

作者信息

Cobbold S P, Thierfelder S, Waldmann H

出版信息

Mol Biol Med. 1983 Oct;1(3):285-304.

PMID:6209527
Abstract

Despite the range of available T cell specific monoclonal antibodies, there are no established rules to predict which might be immunosuppressive. We here describe a series of five rat monoclonal antibodies to a defined T cell antigen (mouse Thy-1) and evaluate their ability to immunosuppress mice. When compared with rabbit anti-lymphocyte globulin, only one of these monoclonal antibodies was able to delay skin allograft rejection and eliminate antibody responses to sheep red blood cells. This antibody was immunosuppressive following intra-peritoneal administration, even though it did not eliminate all of the T cells in vivo. Two factors may be relevant in determining the immunosuppressive properties of this reagent. First, the monoclonal antibody is of the rat IgG2b sub-class, and second, the specificity of the antibody is different to the other monoclonal antibodies in that it reacts with sub-populations of peripheral T cells, thymocytes and non-T cells. In practice, this suggests that to derive suitable monoclonal antibodies for human serotherapy, one should give attention to both the subclass and the fine specificity of the antibody for the target molecule.

摘要

尽管有多种可用的T细胞特异性单克隆抗体,但尚无既定规则来预测哪些可能具有免疫抑制作用。我们在此描述了一系列针对特定T细胞抗原(小鼠Thy-1)的五种大鼠单克隆抗体,并评估了它们免疫抑制小鼠的能力。与兔抗淋巴细胞球蛋白相比,这些单克隆抗体中只有一种能够延迟皮肤同种异体移植排斥反应并消除对绵羊红细胞的抗体反应。即使该抗体在体内并未清除所有T细胞,但腹腔注射后仍具有免疫抑制作用。在确定该试剂的免疫抑制特性时,有两个因素可能与之相关。第一,该单克隆抗体属于大鼠IgG2b亚类;第二,该抗体的特异性与其他单克隆抗体不同,因为它可与外周T细胞、胸腺细胞和非T细胞的亚群发生反应。实际上,这表明为了获得适用于人类血清疗法的单克隆抗体,应该同时关注抗体的亚类及其对靶分子的精细特异性。

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