B7-1抗体阻断B7/CD28信号通路对Pristane肾病的治疗作用

Anti-human B7-1 antibody alleviates mouse lupus-like disease induced by pristane

目的:探讨B7-1抗体阻断B7-1/CD28信号通路对小鼠Pristane肾病的治疗作用。方法:将8周龄雌性C57BL/J6小鼠随机分为3组,正常对照组予生理盐水0.5ml/只,造模组与治疗组予Pristane0.5ml/只后,分别予鼠同型IgG抗体(造模组)或鼠抗人B7-1抗体(治疗组)200μg/只,第10天分别检测局部淋巴结和脾脏中吞噬细胞、树突状细胞的活化及脾脏B细胞表面活化分子的变化;每月定期检测血清中抗核抗体(ANA)及尿蛋白,七个月后处死动物H&E染色观测肾脏病理变化和冰冻切片直接免疫荧光法观察免疫复合物(IC)的沉积情况。结果:第10天,相对于正常对照组、治疗组和造模组小鼠局部淋巴结和脾脏中吞噬细胞、树突状细胞均有不同程度的活化,治疗组活化程度明显低于造模组(P<0.05),脾脏B细胞表面CD21、CD40、CD86等分子上调程度低于造模组(P<0.05);4个月后治疗组和造模组小鼠血清均检测到ANA,但治疗组的血清抗体滴度较造模组低(P<0.05);治疗组7个月后,尿蛋白含量低于造模组,肾脏H&E结果显示治疗组小鼠肾脏病理改变轻于造模组,直接免疫荧光检测可见治疗组免疫复合物荧光强度弱于造模组,正常对照组小鼠肾脏没有明显的病理改变。结论:鼠抗人B7-1抗体对Pristane肾病具有一定的治疗效果。

Objective：To explore the therapeutic effect of mouse anti-human BT-1 antibody on lupus-like disease induced by Pristane in C57BL/J6 mice. Methods： Forty-five of 8-week-old female C57BL/J6 mice were divided into three groups randomly. The control group was injected with 0.5 ml 0. 9 % N. S. While the other two groups with 0.5 ml pristine to induce lupus-like disease. One group with pristane was internented with mouse anti-human B7-1 antibody by caudal vein injection （the intervention group） and the other with mouse isotype IgG（ the model-making group）. The activation of macrophages and dendritic cells in local lymph nodes and spleens and markers on B cells in spleens were measured by FCM, respectively. Antinuclear antibody （ANA） in serum and proteinuria were detected monthly after injection. 7 months after injection, all mice were killed and kidneys were sliced and stained with H＆E or FTTC-labeled IgG to observe the evidence of glomerulonephritis histopathologically. Results： After 10 days, the intervention group and the model-making group macrophage and dendritic cells in lo- cal lymph nodes and spleens of had different levels of activation when compared with those of the control group, the activation of intervention group was significantly lower than in the model-making group （ P 〈 0.05）. The expressions of CD2I, CD40, CD86 on spleen B cell of the intervention group increased lower than ones of the model group （ P 〈 0.05）. The concentration of ANA in mouse sera and protein in uria were showed the same trend. 7 months later, the intervention group was showed less histopathological damages than the model-making group. Immanolluorescence intensity of immune complex（IC） in the intervention group of mouse was weaker than the model-making ones. The mice kidneys of control group mice kidneys had no significant pathological changes and IC couldn＇t be detected. Conclusion： Blocking B7-1/CD28 costimulatory signal pathway, mouse anti-human B7-1 antibody alleviate mouse lupus-like disease induced by Pristane.