RNA干扰树突细胞主要组织相容性复合物1表达后诱导抑制性T细胞对小肠移植耐受的影响

目的探讨RNA干扰树突细胞（Dc）组织相容性复合物1（MHC-1）表达后获得的CD8＋CD28-抑制性T细胞（Ts）对小肠移植免疫耐受的的影响。方法通过siRNA干扰DC MHC—I表达后，诱导获得CD8^＋CD28^-Ts。建立由Wistar大鼠移植到SD大鼠的小肠移植模型36例，随机分为A组（转染实验组）、B组（未转染组，注射普通T细胞）和C组（移植对照组，注射生理盐水）。术后14d，每组各随机挑选6例，取移植大鼠小肠和血液标本行移植小肠组织病理学检查．并检测移植大鼠血清TGF-β、IFN-γ水平及回肠黏膜Na^＋-K^＋-ATP酶活性，观察移植大鼠的存活时间。结果术后第14天，A组移植大鼠血清中TGF—β和IFN-γ表达水平高于B、C组（P〈0．05）。A组大鼠肠黏膜Na^＋-K^＋-ATP酶活性为（6．3±1．0）kU／g，明显高于B组的（3．6±0．9）kU／g和C组的（2．9±1．3）kU／g（P〈0．05）。A组移植小肠病理Parks评分分级明显低于B组和C组（P〈0．05）。A、B和C组移植后大鼠中位生存时间分别为32．0、17．5和21．0d，A组存活时间明显优于B组和C组（P〈0．05）。结论将RNA干扰DCMHC—I表达所获得的CD8^＋CD28^-Ts过继小肠移植大鼠．可以减轻移植大鼠的损伤程度．抑制免疫排斥反应．

Effect of CD8+CD28- suppressor T cells induced by dendritic cell with major histocompatibility complex I expression RNA interference on immune tolerance in rat intestinal transplantation

Objective To investigate the effect of CD8+CD28- suppressor T cells (%) induced by dendritic cell (DC) with major histocompatibility complex 1 (MHC-1) expression RNA interference on immune tolerance in rat intestinal transplantation. Methods The expression level of CD8+CD28- Ts were successfully induced by DC with MHC-1 expression interfered by RNA interference technique under the stimulator of allograft antigen. Orthotopic intestinal transplantation was performed in 36 rats by modified three cuffs method. The recipients were randomly divided into three groups(12 rats in each group) :group A was experimental group with CD8+CD28- Ts being administrated, mixed T cells were injected in group B, while in group C, NS were administrated. On the first day and the seventh day posttransplant, the 36 rats of the 3 groups were administrated through vena dorsalis penis respectively.Six rats were selected randomly from each group and the animals were sacrificed on the 14 th day postoperatively, serum levels of TGF-β, IFN-γ and the values of Na+-K+-ATPase activity of the intestinal graft were assayed and the intestinal pathologie morphology, intestinal allograft survival were observed concerning the remainders. Results On the 14 th day after operation, the expression levels of TGF-β and IFN-γ in group A were significantly up-regulated as compared with those in group B and group C(P<0.05). Na+-K+-ATPase activity in group A was(6.3±1.0) kU/g, much higher than the levels of group B(3.6±0.9)kU/g and group C(2.9±1.3) kU/g and the differences were significant(P<0.05).The data suggested preliminarily that pathological scores of intestinal graft in group A were lower than those in group B and group C. The survival time of the recipients in group A was 32.0 days, much longer than that in group B (17.5 days, P<0.05) and group C(21.0 days, P<0.05). Conclusion CDS+CD28-Ts indueed by DC with MHC-1 expression RNA interference can alleviate acute rejection and lead to immune tolerance in rat intestinal transplantation.