免疫缺陷树突状细胞诱导异种胰岛细胞移植耐受

目的　研究受体来源免疫缺陷树突状细胞(dendriticcell, DC)诱导异种胰岛细胞移植的免疫耐受作用及其机制。方法　从BALB/C小鼠骨髓干细胞诱导分化免疫缺陷DC,负载Wistar大鼠MHC抗原。将上述DC通过尾静脉回输糖尿病小鼠体内(预处理组), 7d后分别将Wistar或SD大鼠胰岛细胞移植于受体鼠肾包膜下。观察移植物存活时间,检测T细胞增殖及TH1 /TH2细胞因子的表达。结果　与对照组相比,预处理组胰岛细胞存活时间明显延长(P < 0. 0 5 ),而以SD大鼠胰岛细胞作为供体的移植物存活时间无明显改变。免疫缺陷DC预处理受体鼠T细胞增殖反应微弱,且TH1 /TH2细胞因子表达明显下降。结论　负载异种MHC抗原的免疫缺陷型DC预处理受体可诱导抗原特异性T细胞无能,以及TH1 /TH2细胞因子的低表达,从而有效地延长异种胰岛细胞存活时间。

Immune-deficient dendritic cells can induce tolerance to transplantation of xenogenic islet cells

Objective To investigate whether host derived immune-deficient dendritic cells (DC) were capable of inducing immunological tolerance to islet xenografts and to ascertain its mechanism. Methods Immune-deficient DC were obtained from marrow of BALB/C mice by inductive differentiation,and loaded with MHC antigen of Wistar rat. The loaded DC were injected into diabetic model mice through tail vein,and,7 days later, islet of Wistar or SD rats were implanted beneath the renal capsule. Survival time of grafts was monitored. Mixed lymphocyte culture and TH1/TH2 cytokine expression were observed. Results Compared to the untreated mice, the survival time of Wistar islets was significantly prolonged in the pretreated mice(P<0.05), but the survival time of SD islets was not significantly prolonged. T lymphocytes of immune-deficient DC pretreated mice showed mild proliferative reaction, and the expression of TH1/TH2 cytokine was significantly lower. Conclusions Immune-deficient DC pretreated with donor MHC antigen can induce antigen-specific nonfunction of T cells and low expression of TH1/TH2 cytokines, and thus can effectively prolong the survival time of islet xenografts.