目的:研究自身组织蛋白vimentin(Vim)和megalin(Meg)在慢性移植肾肾病(CAN)大鼠体内的免疫原性。方法:Lewis大鼠接受F344大鼠供肾移植,每2周检测受体蛋白尿水平观察CAN进程。肾移植后第14、49、98天收获受体脾细胞,检测Vim及Meg特异性IFN-γ分泌细胞的数量;收获受体血清检测Vim及Meg特异性抗体水平。结果:受体肾移植6周后肾功能逐渐衰退,处于CAN病程中。Vim特异性IFN-γ分泌细胞数量逐渐增加,至98 d时其数量比对照孔差异有极显著性(126.0±10.4 vs.24.7±4.3,P〈0.001)。Vim特异性抗体水平肾移植后14 d即显著升高(0.230±0.018 vs.0.063±0.008,P〈0.01),其后缓慢持续升高。CAN大鼠Meg特异性IFN-γ分泌细胞数量无显著性变化。Meg抗体水平直至98 d时比正常大鼠略有上升(0.054±0.006 vs.0.022±0.003,P〈0.05),但远低于同期Vim抗体水平(P〈0.01)。结论:在同种肾移植大鼠CAN病程中,自身蛋白Vim表现强免疫原性而Meg免疫原性极弱。
Objective To investigate the immunogenicity of vimentin (Vim) and megalin (Meg) in murine recipients undergoing CAN. Methods The kidney of Lewis was replaced by a F344 allografi and proteinuria changes of recipients were observed every 2 weeks post-transplantation. The rats were sacrificed at 14th, 49th and 98th day after transplantation, and the spleens and serums were harvested. The frequency of specific IFN--/ secreting T ceils of Vim and Meg were detected by ELISPOT assay. The levels of Vim and Meg IgG antibodies were analyzed by ELISA. Results The proteinuria of recipients began to develop at 6 weeks, increased in intensity in the course of CAN. The number of specific IFN-γ secreting T cells of Vim significantly increased at 98 d(126.0 ± 10.4 vs. 24.7 ± 4.3 ,P 〈 0.001). The sera ELISA analysis revealed a strong production of Vim antibodies at 14 d (0.230 ± 0.018 vs. 0.063 ± 0.008, P 〈 0.O1), and then slowly increased. In contrast, the assays did not detect significant cyto-responses to Meg in CAN recipients. The level of Meg antibody mildly rose till 98 d (0.054±0.006 vs. 0.022 ± 0.003, P 〈 0.05) but was far below the synchronous level of Vim antibody (P 〈 0.01 ). Conclusions In rat recipients undergoing CAN self-protein Vim expressed vigorous immunogenicity and the immune responses against Meg were feeble and hysteretic.