CD103分子介导CD8^＋T淋巴细胞对同种胰岛移植物的损伤

CD103 molecule-mediated pancreatic islet allograft injury induced by CD8 T cells

目的检验CD103分子是否介导了CD8^＋T淋巴细胞对同种移植胰岛的免疫损伤。方法用流式细胞仪检测野生型C57BL／6小鼠外周血CD8^＋T淋巴细胞表达CDl03的情况。以Balb／c小鼠为供者，C57BL／6小鼠为受者，制作同种胰岛移植模型。受者分为3组：M290-SAP组小鼠注射CDl03免疫毒素M290-SAP；M290组小鼠注射抗CDl03单克隆抗体M290；另以仅接受胰岛移植、不注射任何药物的小鼠为未处理组。检测移植胰岛CD3、CD8、CD44和CDl03阳性细胞的表达，检测肠系膜淋巴结中CD3、CD8和CD103阳性细胞的表达。移植物功能丧失或观察期结束时获取移植胰岛，行HE染色和免疫组织化学染色。结果野生型C57BL／6小鼠外周血的CD8^＋T淋巴细胞中有44．06％表达CDl03。未处理组移植胰岛浸润的细胞成分中有29％的CD8^＋T淋巴细胞表达CDl03。M290-SAP组小鼠淋巴细胞不仅丧失了CDl03的表达，而且CD8^＋T淋巴细胞的绝对数量也减少，该组小鼠血糖稳定时间超过100d（未处理组为13d，P〈C0．05），移植胰岛组织学形态良好。结论CD8^＋T淋巴细胞免疫损伤同种移植胰岛必须表达CDl03，CDl03有可能成为胰岛移植抗排斥反应治疗的新靶点。

Objective To test whether the CD103 molecule mediates CD8^＋ T lymphocytes on allogeneie islet graft immune injury. Methods By using flow eytometry, the expression of CD3 in peripheral CD8^＋ T lymphoeytes in wild type C57BL/6 mice was detected. Allogenic islet transplantation models were made using Balb/c donor mice and C57BL/6 recipient mice. Recipients were divided into 3 groups： M290-SAP-treated mice were injected with CDI03 immunotoxin M290- SAP; M290-treated mice were injected with CD103 monoclonal antibody M290; untreated mice were only transplanted islet without any drug treatment. CD3, CDS, CD44 and CD103 positive cells were counted in islet allograft infiltrative lymphocytes. CD3, CDS, and CD103 positive cells were measured in the mesenteric lymph node. The islet allografts were removed and subjected to HE staining and immunohistochemical staining at the time of graft loss or the end of the observation period. Results 44. 06 % peripheral CD8^＋ T cells expressed CD103 in wild-type C57BL/6 mice. 29% CD8^＋ T cells expressed CDI03 in the infiltrative lymphocytes of islet allografts in the untreated mice. In M290- SAP-treated mice, the lymphocytes had no CD103 expression and the ahsolute number of CD8^＋ lymphoeytes was decreased as well. The blood glucose was maintained stable for more than 1.00 days （13 days in untreated group, P〈0. 05） in the M290-SAP-treated mice. Moreover, the transplanted islets retained intact. Conclusion CD103 expression is required for destruction of pancreatic islet allograft by CD8^＋ T cells. CD103 might provide a novel target for therapeutic intervention in islet allograft rejection.