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肝移植前通过预先输注供体大鼠外周血来源的凋亡淋巴细胞诱导免疫耐受。

Induction of immune tolerance by pre-infusion of apoptotic lymphocytes derived from peripheral blood of donor rats before liver transplantation.

作者信息

Feng J F, Chen F, Liu H, Liu J

机构信息

Department of Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou, China.

出版信息

Minerva Chir. 2013 Apr;68(2):183-9.

PMID:23612232

Abstract

AIM

Acute rejection after liver transplantation is usually treated with large doses of immunosuppressants with severe toxic and side-effects, so it is imperative to find an effective method for preventing acute rejection. The aim of this study was to investigate the effects of immune tolerance by pre-infusion of apoptotic lymphocytes derived from peripheral blood of donor rats before liver transplantation.

METHODS

By using male Wistar and Sprague-Dawley (SD) rats as liver donors and recipients, an orthotopic liver transplantation model was established. The rats were divided into Group A (control group) and Group B (apoptotic lymphocytes pre-infusion group). In group B, 1ml apoptotic lymphocytes suspension (concentration 5×107 cells/mL) which were irradiated by X-ray from electron linear accelerator at the absorbed dose of 2.0Gy was pre-infused via the deep dorsal vein of penis on the 7th day before operation. The serum alanine transaminase (ALT), total bilirubin (TBIL), the serum of interleukin (IL) including IL-2, IL-4 and IL-10, liver pathological changes, and survival time were analysed.

RESULTS

The survival in Group A were 7~~13d, with the median survival time (MST) of 11d, and in Group B were 37~~60 d, with the MST of 60 d. There were significant differences between the two groups in survival (P <0.001). There were significant differences between the two groups in ALT (P <0.01) and TBIL (P <0.01). Microscopic inspection revealed that severe acute rejection in the Group A, but no sign of acute rejection was observed in the Group B in the 7th day postoperation. The levels of IL-2 were increased after operation in two groups, but was obviously increased in the 7th (P <0.01) and 10th (P <0.001) day postoperation in Group A. The levels of IL-4 and IL-10 in Group A were declined but were increased in the 7th (P <0.01) and 10th (P <0.001) day postoperation in Group B.

CONCLUSION

Preinfusion of apoptotic lymphocytes derived from peripheral blood of donor rats can induce immune tolerance in liver transplantation. Increased expression of Th2 cytokines (IL-4 and IL-10) may plays an important role in inducing immune tolerance.

摘要

目的

肝移植术后急性排斥反应通常采用大剂量免疫抑制剂治疗，其毒副作用严重，因此寻找有效的预防急性排斥反应的方法势在必行。本研究旨在探讨肝移植前输注供体大鼠外周血凋亡淋巴细胞诱导免疫耐受的效果。

方法

以雄性Wistar大鼠和Sprague-Dawley（SD）大鼠作为供肝和受体，建立原位肝移植模型。将大鼠分为A组（对照组）和B组（凋亡淋巴细胞预输注组）。B组于术前第7天经阴茎背深静脉预输注1ml经电子直线加速器以2.0Gy吸收剂量X线照射的凋亡淋巴细胞悬液（浓度5×107细胞/mL）。分析血清丙氨酸转氨酶（ALT）、总胆红素（TBIL）、包括白细胞介素（IL）-2、IL-4和IL-10在内的血清白细胞介素、肝脏病理变化及生存时间。

结果

A组大鼠存活7～13天，中位生存时间（MST）为11天；B组大鼠存活37～60天，MST为60天。两组大鼠的生存率差异有统计学意义（P<0.001）。两组大鼠的ALT（P<0.01）和TBIL（P<0.01）差异有统计学意义。显微镜检查显示，A组有严重的急性排斥反应，而B组在术后第7天未观察到急性排斥反应迹象。两组术后IL-2水平均升高，但A组在术后第7天（P<0.01）和第10天（P<0.001）明显升高。A组IL-4和IL-10水平下降，而B组在术后第7天（P<0.01）和第10天（P<0.001）升高。