携带供者抗原的第三方树突状细胞诱导小鼠皮肤移植耐受的研究

目的 了解携带供者抗原的第三方树突状细胞(DC)是否具有与供者源未成熟DC相似的免疫功能.方法 雌性C57BL/6小鼠、BALB/c小鼠和昆明小鼠分别为皮肤移植的供者、受者和第三方.将40只BALB/c小鼠分为对照组、环磷酰胺组、供者源未成熟DC组、第三方未成熟DC组、携带供者抗原第三方DC组,每组8只.后4组大鼠皮肤移植术前4 d用环磷酰胺(200 mg/kg)预处理,对照组同法给予等量等渗盐水.后3组术前2 d用1 ml相应DC悬液(1×107个/ml)预处理,并在术后12 d重复给予1 ml DC悬液(1×107个/ml)1次;前2组于上述2个时相点同法给予等量等渗盐水.记录各组皮片平均成活时间(MST)并于术后5 d对皮片进行组织学观察.结果 与对照组(16.1±3.5)d比较,供者源未成熟DC组和携带供者抗原第三方DC组小鼠移植皮片的MST明显延长,分别为(38.3±7.7)、(34.9±7.7)d(P＜0.01);携带供者抗原第三方DC组与供者源未成熟DC组皮片的MST相近(P＞0.05),但与第三方未成熟DC组(23.7±2.7)d比较,差异有统计学意义(P＜0.05).镜下见携带供者抗原第三方DC组移植皮片结构较清楚、排列有序,与供者源未成熟DC组情况相近.结论 携带供者抗原的第三方DC与供者源未成熟DC,均可在一定程度上建立抗原特异性免疫耐受.

Study on the induction of skin transplantation tolerance against rejection in mice by third-party dendritic cells loaded with donor's antigens

OBJECTIVE: To investigate whether the third-party dendritic cells (DC) incubated with donor's antigens posess the similar immune functions with donor derived immature DC. METHODS: Female C57 BL/6, BALB/c and Kunming mice were used as skin transplant donors, recipients and third-party, respectively. Forty BALB/c mice were randomly divided into A (normal control), B (cyclophosphamide administration), C (CTX and donor derived immature DC), D (CTX and third-party immature DC), E (CTX and third-party DC loaded with donor's antigens) groups, with 8 mice in each group. The mice in group B, C, D and E were given CTX (200 mg/Kg) 4 days before operation, while those in group A were given equivalent amount of normal saline(NS). Then in group C, D and E, DC at a dose of 1 x 10(7)/ml were intraperitoneally injected with 2 days before grafting and 12 days after operation, but the mice in group A and B were given NS in the same manner. Mean survival time (MST) of skin grafts was recorded, and biopsies of grafts on 5 and 10 post-operation days (POD) were harvested for histologic examination. RESULTS: Compared with group A (16.1 +/- 3.5)d], MST of skin grafts in group C (38.3 +/- 7.7) d] and E (34.9 +/- 7.7) d] were significantly prolonged ( P < 0.01), while no obvious difference was observed between group C and E( P > 0.05), but there was statistically significant difference in MST between group D (23.7 +/- 2.7) d] and E ( P < 0.05). In addition, clear epithelial structure and infiltration of inflammatory cells were observed in specimens from both groups C and E. CONCLUSION: Both donor derived immature DC and third-party DC loaded with donor's antigens can partly induce donor specific transplantation tolerance.