Cobbold S P, Jayasuriya A, Nash A, Prospero T D, Waldmann H
Nature. 1984;312(5994):548-51. doi: 10.1038/312548a0.
A major aim in immunology has been to understand how the immune system evokes characteristic responses to infection, foreign tissue grafts and tumours. The current view of immunoregulation is based mainly on studies of lymphocyte subsets, either in vitro or by adoptive transfer to irradiated recipients. Many reagents are available for defining T-cell subsets, but only recently have there been helper T-cell-specific antibodies against the mouse equivalent of the Leu3/T4 (man) and W3/25 (rat) antigens. It is clear that monoclonal antibodies will eventually replace antilymphocyte globulin for immunosuppression in organ grafting, but although there has been some clinical success, most monoclonal reagents cause only transient reductions in their target cells in vivo. This uncertainty in the potency of monoclonal antibodies has led some workers to consider them as targeting agents for such highly cytotoxic drugs as ricin A (ref. 21). We show here that unmodified monoclonal antibodies can be extremely effective at depleting cells in vivo and can be used for the selective manipulation of different aspects of the immune response.
免疫学的一个主要目标是了解免疫系统如何对感染、异体组织移植和肿瘤产生特征性反应。目前对免疫调节的看法主要基于对淋巴细胞亚群的研究，这些研究要么在体外进行，要么通过将淋巴细胞过继转移给受辐照的受体来进行。有许多试剂可用于定义T细胞亚群，但直到最近才有针对小鼠中相当于Leu3/T4（人类）和W3/25（大鼠）抗原的辅助性T细胞特异性抗体。很明显，单克隆抗体最终将取代抗淋巴细胞球蛋白用于器官移植中的免疫抑制，但是尽管已经取得了一些临床成功，但大多数单克隆试剂在体内仅能使它们的靶细胞暂时减少。单克隆抗体效力的这种不确定性导致一些研究人员将它们视为诸如蓖麻毒素A等高度细胞毒性药物的靶向剂（参考文献21）。我们在此表明，未修饰的单克隆抗体在体内耗尽细胞方面可能极其有效，并且可用于选择性操纵免疫反应的不同方面。
