Treatment of murine lupus with monoclonal anti-T cell antibody.
Treatment of murine lupus with monoclonal anti-T cell antibody.
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用单克隆抗 T 细胞抗体治疗小鼠狼疮。
DOI：
10.4049/jimmunol.134.2.852
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发表时间：
1985
影响因子：
4.4
通讯作者：
W. Seaman
中科院分区：
文献类型：
--
作者：
D. Wofsy;J. Ledbetter;P. Hendler;W. Seaman
对3株自身免疫小鼠（MRL/lpr、NZB/NZW和BXSB）反复注射大鼠单克隆抗T细胞抗体（anti-Thy-1.2），以确定1)靶细胞耗损的程度和持续时间，2)T细胞耗损对自身免疫过程的影响，以及3)宿主对单克隆抗体免疫应答的程度和后果。从疾病早期开始，每2周给小鼠注射6毫克抗thy -1.2。治疗在所有三种毒株中产生了循环T细胞的大量减少。治疗对MRL/lpr小鼠有益。它减少了淋巴结病变，降低了自身抗体浓度，延缓了肾脏疾病，延长了寿命。相比之下，治疗并没有改善NZB/NZW小鼠的自身免疫，而且在BXSB小鼠中引起致死性过敏反应。这些发现表明，单克隆抗淋巴细胞抗体可以作为特异性探针来检测参与自身免疫的细胞。此外，他们说明了单克隆抗淋巴细胞抗体的潜在治疗价值，当一个致病细胞亚群可以确定。然而，相同的抗体可能具有广泛的作用，从有效到严重毒性，甚至在具有共同临床特征的疾病中也是如此。
Three strains of autoimmune mice (MRL/lpr, NZB/NZW, and BXSB) were treated with repeated injections of rat monoclonal anti-T cell antibody (anti-Thy-1.2) in order to determine 1) the extent and duration of target cell depletion, 2) the effect of T cell depletion on the course of autoimmunity, and 3) the magnitude and consequences of the host immune response to the monoclonal antibody. Mice were treated with 6 mg of anti-Thy-1.2 every 2 wk beginning early in their disease. Treatment produced a substantial reduction in circulating T cells in all three strains. Therapy was beneficial in MRL/lpr mice. It reduced lymphadenopathy, lowered autoantibody concentrations, retarded renal disease, and prolonged life. In contrast, treatment did not improve autoimmunity in NZB/NZW mice, and it caused fatal anaphylaxis in BXSB mice. These findings demonstrate that monoclonal antilymphocyte antibodies can serve as specific probes to examine the cells that contribute to autoimmunity. Moreover, they illustrate the potential therapeutic value of monoclonal antilymphocyte antibodies when a pathogeneic cell subset can be identified. However, the same antibody may have a broad range of effects, from efficacy to severe toxicity, even in diseases that share clinical features.