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单克隆抗T细胞(T12)抗体治疗重症联合免疫缺陷中的移植物抗宿主病:抗体靶向及补体在CD8 + 细胞毒性T细胞表面的激活

Monoclonal anti-T cell (T12) antibody treatment of graft-versus-host disease in severe combined immunodeficiency: targeting of antibody and activation of complement on CD8+ cytotoxic T cell surfaces.

作者信息

Blomquist M D, Boggards M, Hanson I C, Rosenblatt H M, Pollack M S, Hawkins E, Ritz J, Shearer W T

机构信息

Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030.

出版信息

J Allergy Clin Immunol. 1991 May;87(5):1029-33. doi: 10.1016/0091-6749(91)90427-p.

Abstract

We report a 6-month-old male child with severe combined immunodeficiency who received an unirradiated blood transfusion and developed acute, severe graft-versus-host disease (GVHD), for which he received monoclonal anti-T cell (anti-T12) antibody treatment. The GVHD was manifested by a confluent maculopapular rash and increased liver function tests and was documented by skin biopsy. Separation of peripheral blood mononuclear cells forming rosettes with sheep red blood cells revealed engrafted T cells having the nonrelated HLA type of the blood donor. The patient was treated with intravenous monoclonal anti-T12 in a dose of 0.3 mg/kg/day for 5 days. An in vivo effect of the anti-T12 was suggested by clinical improvement of his skin rash and return of the liver transaminases to the normal range. Moreover, human complement components, activated C3 and C4, were detected by fluorescence microscopy on the surfaces of the engrafted CD8+ lymphocytes on the skin biopsy specimens. Also, with a biotin-avadin assay, the presence of the anti-T12 was detected on these same cells. These studies document not only the in vivo targeting of monoclonal anti-T12 antibody to cytotoxic T cells producing GVHD but also the activation of complement on these cells.

摘要

我们报告了一名6个月大的患有严重联合免疫缺陷的男童,他接受了未照射的输血,并发生了急性严重移植物抗宿主病(GVHD),为此他接受了单克隆抗T细胞(抗T12)抗体治疗。GVHD表现为融合性斑丘疹和肝功能检查指标升高,并经皮肤活检证实。与绵羊红细胞形成玫瑰花结的外周血单个核细胞分离显示,移植的T细胞具有献血者不相关的HLA类型。患者接受静脉注射单克隆抗T12治疗,剂量为0.3mg/kg/天,共5天。皮疹临床改善以及肝转氨酶恢复到正常范围提示了抗T12的体内效应。此外,通过荧光显微镜在皮肤活检标本上移植的CD8+淋巴细胞表面检测到了人类补体成分、活化的C3和C4。同样,通过生物素-抗生物素蛋白测定法,在这些相同的细胞上检测到了抗T12的存在。这些研究不仅证明了单克隆抗T12抗体在体内靶向产生GVHD的细胞毒性T细胞,还证明了这些细胞上补体的激活。

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