摘要
目的 观察共刺激分子阻断剂CD80单克隆抗体(CD80mAb)在协同未成熟树突细胞(imDC)诱导同种异体大鼠胰十二指肠移植免疫耐受中的作用。方法 建立糖尿病大鼠胰十二指肠移植动物模型;4E5杂交瘤细胞株BABIMC小鼠腹腔注射,抽取腹水,分离纯化后获得CD80mAb;分离供体大鼠骨髓来源DC细胞前体,经GM—CSF、IL-4体外刺激后。再加入IL-10共培养,鉴定为imDC;移植前7d,将2×10^6imDC经静脉途径注射至受体体内,同时分别给予生理盐水1ml、CD80mAb5mg连续14d。结果 四组受体大鼠移植后中位生存时间分别为12.7d、32.4d、50.2d、92.0d,实验组存活时间明显延长;组织学观察发现移植后7dCD80mAb+imDC组移植物形态尚完整,淋巴细胞浸润减少;混合淋巴细胞反应证实移植后7dCD80mAb+imDC组供受体间呈低反应性。结论 共刺激分子阻断剂CD80mAb能够协同imDC诱导受体T细胞对移植物的免疫耐受,降低宿主对移植物的急、慢性排斥反应,延长移植物的存活时间。
Objective To observe the combination effect of CD80mAb and immature dendritic cells as inducement for donor-specific immune tolerance in an allograft SD rat pancreaticoduodenal transplantation model. Method A diabetic SD rat model of pancreasticoduodenal transplantation was established; 2 × 10^6 1B1 and 4E5 hybridoma cell strain was injected into BABL/C mice, then, CD80mAb from ascites produced in BABL/C mice were purified; The pre-DC was dissociated from donor marrow, and stimulated with GM-CSF and IL-4 in vitro. After co-cultured with IL-10 for 8 days, we detected the expression of co-stimulation molecular and MHC-Ⅱ. 7 days before transplantation, 2 × 10^6 imDC was injected to aLl recipitients. 1 ml NS,5mg of CD80mAb were injected on the day imDC infused and 0. 5 mg per day for the following consecutive 14 days. Result The median survival time of CD80mAb + imDC groups were 92. 0 days. Histological examination of pancreaticoduodenal graft in experimental group found that at the 7^th day after transplantation, the structure of pancreas glandular lobule exist, the allograft infiltration of leukocytes was inhibited. The host showed low response to the graft when detected by MLR. Conclusion The co-stimulation blockade CD80mAb can synergistically enhance imDC to induce donor-specific T cell tolerance with donor graft, suppress acute and chronic rejection by host versus graft and increase the survival time of pancreaticoduodenal allograft.
出处
《中华普通外科杂志》
CSCD
北大核心
2007年第6期457-460,共4页
Chinese Journal of General Surgery
基金
苏州市卫生局科教兴卫资助项目(SWQ09)
关键词
胰腺移植
免疫耐受
大鼠
CD80单克隆抗体
树突细胞
Pancreas transplantation
Immune tolerance
Rat
CD80 monoclonal antibodies
Dendritic cells