Influence of up-regulated Foxp3 expression on regulatory T cells function and kidney transplantation chronic rejection reaction in rat model / 中华器官移植杂志

ABSTRACT

Objective To explore the influence of up-regulated Foxp3 on Treg function and kidney transplantation chronic rejection reaction in rat model.Method The kidney transplantation chronic rejection reaction rat model was established.The F344 kidney was transplanted to Lewis rats,and retroviruses highly expressing Foxp3 were constructed.The Banff 97 hierarchical diagnostic criteria were used to diagnose chronic renal allograft nephropathy (CAN).The rat models were divided into three groups by random number table.In experimental group,the pSCV-BsdRFP-FoxP3 retroviruses were injected into the rats via the tail vein after operation.In negative control group,the pSCV-BsdRFP retroviruses were injected into the rats via the tail vein after operation.In blank group,the normal saline was injected into the rats via the tail vein after operation.Enzyme-linked immunosorbent assay (ELISA) was used to detect the changes of interleukin-10 (IL-10) and tumor necrosis factor-β (TGF-β) immediate,1,2,3,and 4 weeks after operation.The rats were killed at 4th week after operation,and kidney tissues were taken out for pathological examination.Result The pathological changes of CAN were observed at 4th week.The typical chronic rejection change was seen at 12th week.The levels of IL-10 and TGF-β were increased,and reached the peak at 3rd week.The levels of IL-10 and TGF-β in experimental group were higher than in negative control group and blank group at 1st,2nd,3rd,and 4th week.At 4th week,obviously different degrees of intimal thickening,and mild hyperplasia of interstitial fibers,glomerular sclerosis and infiltration with lymphocytes and plasma cells were observed in the three groups.In the experimental group,the lesions were mildest,and apparent neointimal hyperplasia was found.Conclusion pSCV-BsdRFP FoxP3 retroviruses can reduce the kidney transplantation chronic rejection reaction in rat model,and have the potential treatment effect.