过继回输耐受性树突状细胞促进大鼠肝移植免疫耐受的应用研究

Application study on adoptive transfusion of tolerogenic dendritic cells in promoting immune tolerance of liver transplantation in rat models

    摘要
  • 摘要:
      目的  探讨耐受性树突状细胞（tolDC）在肝移植免疫耐受诱导中的作用。
      方法  建立自发耐受Brown Norway（BN）→Lewis，耐受组，n=6和急性排斥反应（AR）（Lewis→BN）大鼠肝移植模型，AR模型大鼠中实验组进行tolDC回输（tolDC组，n=6），对照组不进行干预（AR组，n=6）。观察各组大鼠术后生存时间，对各组大鼠移植肝组织进行病理学检查；采用流式细胞术检测各组大鼠外周血、移植肝、脾脏、淋巴结髓样树突状细胞（mDC）和浆细胞样树突状细胞（pDC）的表达情况；采用酶联免疫吸附试验检测各组大鼠血清白细胞介素（IL）-10和干扰素（IFN）-γ的表达情况。
      结果  AR组大鼠病理学表现主要为移植肝炎症细胞浸润和组织结构紊乱，生存时间7~14 d；tolDC组与耐受组大鼠移植肝组织基本正常，最长生存时间超过100 d。与AR组比较，耐受组和tolDC组大鼠外周血、移植肝、脾脏、淋巴结CD11+mDC水平均下降（均为P < 0.05），且CD11+mDC表面CD86、主要组织相容性复合体（MHC）Ⅱ表达水平均降低（均为P < 0.05）。与AR组比较，耐受组和tolDC组大鼠外周血、移植肝、脾脏、淋巴结中pDC水平均升高（均为P < 0.05），同时pDC表面的MHCⅡ表达水平均降低（均为P < 0.05）。与AR组比较，耐受组和tolDC组大鼠血清IL-10的表达水平均升高、IFN-γ的表达水平均降低（均为P < 0.05）。
      结论  作为tolDC亚群，mDC和pDC在大鼠肝移植术后移植物免疫耐受的发生过程中均具有正向调节作用。

     

    Abstract:
      Objective  To investigate the role of tolerogenic dendritic cell (tolDC) in inducing immune tolerance in liver transplantation.
      Methods  Liver transplantation rat models of spontaneous tolerance Brown Norway (BN)→Lewis, tolerance group, n=6 and acute rejection (AR) (Lewis→BN) were established. In AR rat models, tolDC transfusion was performed in the study group (tolDC group, n=6) and no intervention was given in the control group (AR group, n=6). The survival time of rats in each group was observed. The transplant liver tissues of rats were prepared for pathological examination in each group. The expression of myeloid dendritic cell (mDC) and plasmacytoid dendritic cell (pDC) in rat peripheral blood, transplant liver, spleen and lymph nodes in each group was detected by flow cytometry. The expression levels of serum interleukin (IL)-10 and interferon (IFN)-γ in each group were measured by enzyme-linked immune absorbent assay.
      Results  Pathological manifestations of rats in the AR group mainly included inflammatory cell infiltration and tissue structural disorder in transplant liver, and the survival time was 7-14 d. In the tolDC and tolerance groups, the transplant liver tissues were almost normal, and the longest survival time exceeded 100 d. Compared with the AR group, the expression levels of CD11+mDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05), and those of CD86 and major histocompatibility complex (MHC)Ⅱon the surface of CD11+mDC were also significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of pDC in peripheral blood, transplant liver, spleen and lymph nodes of rats were significantly up-regulated in the tolerance and tolDC groups (all P < 0.05), whereas those of MHCⅡon the surface of pDC were all significantly down-regulated (all P < 0.05). Compared with the AR group, the expression levels of serum IL-10 were significantly up-regulated, and IFN-γ were significantly down-regulated in the tolerance and tolDC groups (all P < 0.05).
      Conclusions  As tolDC subsets, mDC and pDC play a positive role in regulating the incidence of graft immune tolerance in rats after liver transplantation.

     

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