INVIVO USE OF MONOCLONAL-ANTIBODIES AGAINST MURINE T-CELL ANTIGENS
INVIVO USE OF MONOCLONAL-ANTIBODIES AGAINST MURINE T-CELL ANTIGENS
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DOI：
10.1016/0090-1229(89)90162-1
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发表时间：
1989-09-01
期刊：
影响因子：
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通讯作者：
AUCHINCLOSS, H
中科院分区：
文献类型：
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作者：
GHOBRIAL, RRM;BOUBLIK, M;AUCHINCLOSS, H
通过实验寻找抗t细胞单克隆抗体在小鼠体内的最佳使用条件。采用不同亚类（IgG2b、IgG2a和IgM）和种类（大鼠或小鼠）的抗l3t4 （CD4）和抗lyt2 （CD8）抗体。结果表明：(1)无论受体胸腺存在与否，腹腔注射与静脉注射不同的抗体获得相同的血清水平；（ii）反复使用大鼠IgM抗l3t4或大鼠IgG2b抗lyt2抗体治疗后，无法检测每种抗体的血清水平；（iii）用这些抗体在体内治疗会导致靶细胞裂解，靶抗原掩蔽而不破坏细胞，或靶抗原调节而不破坏细胞，并且特定抗体的特定作用不能通过其特异性的同型来预测；（iv）体内补体C5成分和抗体依赖性细胞介导的细胞毒性均未介导GK1.5抗体的作用；(v)抗体体内效价的剂量依赖性曲线不能通过体外测定预测；（vi）胸腺细胞被单克隆抗体耗尽，使用的抗体比消耗周围淋巴细胞所需的抗体多1000倍；（vii）未去胸腺小鼠靶T细胞耗竭后的返回率取决于抗体的剂量；（viii）胸腺切除术延长了大多数抗体的作用，但不是所有抗体。在去胸腺的小鼠中。CD8+细胞在耗尽后很长一段时间内几乎检测不到，而CD4+细胞在最初完全耗尽后恢复到原始水平的约30%，并在一段时间内保持不变。这些结果为在小鼠体内有效使用单克隆抗t细胞抗体提供了有用的数据。他们强调，在没有实际在体内测试的情况下，很难预测单克隆抗体在体内的作用。它们包括对单克隆抗体的作用机制和胸腺切除术在延长其作用中的作用的新见解。他们描述了抗体消耗胸腺细胞的未被识别的能力。
Experiments were performed seeking conditions for the optimum use of anti-T cell monoclonal antibodies in vivo in mice. Anti-L3T4 (CD4) and anti-Lyt2 (CD8) antibodies of different subclasses (IgG2b, IgG2a, and IgM) and species (rat or mouse) were used. The results showed that (i) intraperitoneal compared to intravenous administration of the different antibodies achieved the same serum levels whether in the presence or absence of the recipient''s thymus; (ii) repeated treatment with a rat IgM anti-L3T4 or a rat IgG2b anti-Lyt2 antibody was followed by inability to detect serum levels of each antibody; (iii) in vivo treatment with these antibodies caused target cell lysis, target antigen masking without cell destruction, or target antigen modulation without cell destruction and the particular effect of a given antibody could not be predicted by its isotype of specificity; (iv) neither the C5 component of complement nor antibody-dependent cell-mediated cytotoxicity mediated the action of GK1.5 antibody in vivo; (v) dose-dependent curves of in vivo potency of a given antibody could not be predicted by in vitro assays; (vi) thymocytes were depleted by monoclonal antibody treatment by using 1000-fold more antibody than needed to deplete peripheral lymphocytes; (vii) the rate of return of target T cells after depletion in nonthymectomized mice depended on the dose of the antibody; and (viii) thymectomy prolonged the effect of most, but not all antibodies. In thymectomized mice. CD8+ cells remained almost undetectable for prolonged periods of time after depletion while CD4+ cells returned to approximately 30% of their original level and remained constant over time after initial complete depletion. These results provide useful data for the effective use of monoclonal anti-T cell antibodies in mice. They stress the difficulty of predicting the in vivo effects of monoclonal antibodies without actually testing them in vivo. They include new insights into mechanisms of action of monoclonal antibodies and the role of thymectomy in prolonging their effect. They describe the unrecognized ability of antibodies to deplete thymocytes.