Shimamine R, Shibata R, Ozono Y, Harada T, Taguchi T, Hara K, Kono S
Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Nephron. 1998;78(3):310-8. doi: 10.1159/000044941.
We investigated the effects of anti-CD4 monoclonal antibody (mAb) and/or anti-CD8 mAb in ddY mice, an animal model of spontaneous IgA nephropathy. Female ddY mice were treated with 18 intravenous injections of anti-CD4 and/or anti-CD8 mAb at 2-week intervals. This was based on our observation that a single injection of anti-CD4 mAb or anti-CD8 mAb caused a selective depletion in CD4+ T cells for 2 weeks and CD8+ T cells for 4 weeks, respectively. The level of proteinuria, serum IgA, and changes in the histopathological features of renal tissue samples were assessed in treated mice between the age of 4 and 40 weeks. The level of proteinuria increased with age, but there was not significant difference among the groups. No animal developed microhematuria throughout the study. Treatment with anti-CD4 mAb produced a mild to moderate level of mesangial hypertrophy at 20 and 40 weeks, similar to the results in untreated mice. The lowest degree of mesangial hypertrophy occurred in mice treated with anti-CD8 mAb up to the age of 40 weeks. Treatment with a combination of anti-CD4 and anti-CD8 mAbs produced effects that were similar to those observed on treatment with anti-CD8 mAb alone. Our results suggest that CD8+ T cells mediate mesangial proliferation and the progression of nephropathy in ddY mice.
我们在ddY小鼠（一种自发性IgA肾病动物模型）中研究了抗CD4单克隆抗体（mAb）和/或抗CD8 mAb的作用。雌性ddY小鼠每隔2周接受18次抗CD4和/或抗CD8 mAb静脉注射。这是基于我们的观察，即单次注射抗CD4 mAb或抗CD8 mAb分别导致CD4+ T细胞选择性耗竭2周和CD8+ T细胞选择性耗竭4周。在4至40周龄的受试小鼠中评估蛋白尿水平、血清IgA以及肾组织样本组织病理学特征的变化。蛋白尿水平随年龄增加，但各组之间无显著差异。在整个研究过程中，没有动物出现镜下血尿。抗CD4 mAb治疗在20周和40周时产生轻度至中度的系膜增生，与未治疗小鼠的结果相似。在40周龄前，抗CD8 mAb治疗的小鼠系膜增生程度最低。抗CD4和抗CD8 mAbs联合治疗产生的效果与单独使用抗CD8 mAb治疗时观察到的效果相似。我们的结果表明，CD8+ T细胞介导ddY小鼠的系膜增殖和肾病进展。
