TGFβ1基因修饰供者树突状细胞降低移植心脏RANTES表达

Injection of TGFpl-Gene Modified Donor Dendritic Cells Inhibits the Expression of RANTES in Rat Cardiac Grafts

目的 探讨移植前输注入TGFβ1基因修饰树状细胞(dendritic cell,DC)对移植心脏正常T细胞表达和分泌的活化调节因子(RANTES)表达的影响。方法 TGFβ1-pcDNA3重组质粒转染供者DC,静脉输注异体大鼠,1周后检测TGFβ1-DC在受者脾和淋巴结的分布。TUNEL法检测受者大鼠脾T细胞凋亡水平,并检测受者脾RANTES表达的变化;同时另一部分输注大鼠接受同种异体心脏移值,观察DC输注后移植心脏存活时间变化,比较移植后不同时间排斥反应级别,免疫组化检测移植心脏 RANTES的表达。结果 TGFβ1-DC输注受者后,1周内可在脾和淋巴结内形成微嵌合,并有效诱导T细胞的凋亡。TGFβ1-DC输注大鼠移植后排斥反应明显低于对照组,移植心脏存活时间明显延长,并发现移植心脏RANTES表达明显低于对照组。结论 TGFβ1-DC能有效降低移植心脏RANTES表达,增强移植心脏免疫耐受性。

Purpose: To study the effects of injection of TGFβ1 gene modified dendritic cells (TGFβ1 DC) on the expression RANTES (regulated by activation, normal Tcell expressed and secreted) in rat cardiac grafts. Methods: The recombinant TGFβ1-pcDNA3 plasmid was transfected into the immature Lewis DCs mediated by DOTAP and the TGFβ1-DCs were injected into F344 rat through tail vein. The distribution of TGFβ1-DC in spleens and lymph nodes of recipient rats was observed one week after injection and expression of RANTES in spleen was detected. Apoptosis of T cells in recipient spleen was analyzed by TUNEL staining. Meanwhile the TGFβ1-DC injected F344 rats were received cardiac transplantation from Lewis rats. The survivals of the allografts were observed and rejection grades at different times after transplantation were assayed. The expression of RANTES was detected by immunohistochemistry. Results: The injected DC were chimerised in the recipient spleen and lymph node one week after injection and could effectively induce apoptosis of T cells. Compared with those in control groups, the rejection grades were decreased and the allografts survival were prolonged in TGFβ1-DC group. We also found that TGFβ1-DC injection inhibited the expression of RANTES in rat cardiac allografts. Conclusions: TGFβ1 gene modified DC could obviously inhibite the expression of RANTES and enhance the tolerogenicity of cardiac allografts.