Jagged1在树突状细胞介导淋巴细胞诱导皮肤移植免疫耐受中的作用

Effect of Jagged1 on the immunotolerance of skin transplantation induced by dendritic cell-mediated lymphocytes

目的:探讨Jagged1在树突状细胞(DC)介导淋巴细胞诱导同种异基因皮肤移植免疫耐受中的作用。方法:C57BL/6小鼠为供体,BALB/c小鼠为受体行皮肤移植术,受体小鼠分为对照组,Jagged1+DAPT处理组和Jagged1处理组。取供体小鼠淋巴细胞加入经rmIL-4和rmGM-CSF处理9 d的供体骨髓细胞中,当日和隔日分别加入Jagged1和DAPT。2 d后取淋巴细胞,于皮肤移植第0天、第2天和第4天,经尾静脉注入受体小鼠。观察皮肤移植物存活时间和移植物病理变化,并检测受体小鼠混合淋巴细胞反应和迟发型超敏反应。结果:Jagged1处理组的皮肤移植物平均存活83.6 d,显著长于其它各组(P<0.01);Jagged1处理组移植皮片内浸润的炎细胞数量明显减少;在混合淋巴细胞反应中,Jagged1处理组小鼠对供体小鼠呈现低反应性(P<0.01),而对第三方无关供体KM小鼠表现强烈的增殖反应,Jagged1处理组小鼠在迟发型超敏反应中也表现出显著的低反应性(P<0.01)。结论:输注Jagged1联合DC处理的淋巴细胞诱导受体获得供体抗原特异性的免疫耐受。

Aim：To explore the effect of Jaggedl on the skin allograft immunotolerance induced by dendritic cell-mediated lymphocytes. Methods： The skin grafts from C57BL/6 mice were transplanted to BALB/c mice. The recipients were divided into three groups： control group, Jaggedl plus DAPT group and Jaggedl group. The lymphocytes of the donor mice were added to bone marrow cells of the donor which had been pretreated with rmlL-4 and rmGM-CSF for 9 d. Meanwhile, Jaggedl and DAPT were added to them on day 1 and day 2 respectively. Two days later the lymphocytes were collected and injected into the recipient mice via tail vein on day 0, day 2 and day 4 after skin transplantation. Then the survival time and pathological change of skin graft was observed, mixed lymphocyte reaction （MLR） anddelayed type hypersensitivity （DTH） of the recipient were detected. Results： The average survival time of skin graft in Jaggedl group was 83. 6 d, which was significantly prolonged compared with other groups （P 〈0. 01）. The inflammatory cells of Jaggedl group in the skin graft were significantly reduced. The recipient of the Jaggedl group appeared hyporesponsiveness to the donor（ P 〈 0. 01 ）, but hyperresponsive- ness to KM mice in MLR. They were showed distinguished hyporesponsiveness also in DTH（P 〈0. 01 ）. Conclusion： Infusion of the lymphocytes treated by Jaggedl combined with dendritic cells can induce recipients to obtain immunotolerance of donor antigenic specificity.