转化生长因子-β_1基因修饰树突状细胞诱导异种胰岛移植耐受

TGF-β_1 gene modified dendritic cells induced tolerance in islet xenotransplantation

目的探讨转化生长因子(TGF)-β1基因修饰的树突状细胞(dendriticcell,DC)对异种胰岛移植的免疫耐受诱导作用。方法分别从BALB/C小鼠骨髓培养未成熟DC及成熟DC,将TGFβ1-pcDNA3质粒转染未成熟DC。分别将成熟DC和TGFβ1-DC负载Wistar大鼠胰岛抗原回输糖尿病小鼠体内,7d后将大鼠胰岛移植于左肾包膜下,观察移植物存活、T细胞增殖反应和细胞毒效应。结果以Wistar大鼠为供体,正常小鼠的移植物存活时间为(10·2±1·1)d,成熟DC预处理后移植物存活时间明显缩短(7·0±1·3)d,P<0·05,而TGFβ1-DC预处理后存活时间显著延长(45·2±4·5)d,P<0·05。以SD大鼠作为供体时,移植物存活时间与对照组之间相比差异无统计学意义(11·3±1·2)d,P>0·05。成熟DC预处理鼠T细胞增殖活性和细胞毒效应显著增强(SI=6·92,KRmax=73%,P<0·05),TGFβ1-DC预处理后上述效应明显降低(SI=1·13,KRmax=6·9%,P<0·05),但两组对SD大鼠的效应无明显差别。结论TGF-β1基因修饰DC回输受体可诱导异种胰岛移植耐受,其机制与T细胞无能相关。

Objective To investigate whether TGF-β1 gene modified dendritic cells could induce immune tolerance in islet xenotransplantation. Methods Mature and immature DC were cultured from bone marrow of BALB/C mice, and then transfected the immature DC with TGFβ1 gene. Two kinds of DC were loaded with antigen of islet from Wistar rats, and injected into BALB/C mice with diabetes. After one week, the islets of Wistar or SD rats were transplanted under the capsular of left kidney. Survival time of grafts, proliferation and cytotoxicity of host T cell were evaluated. Results Grafts survival time in normalgroup was （10.2±1.1） d, （7.0±1.3） din mature DC pretreated group （P〈0.05） and （45.2±4.5） din TGFβ1-DC treated group （P 〈0. 05） , when Wistar rats were used as donors. In cases of SD rats grafts survival did not change （ 11.3 ± 1.2 ） d, P 〉 0. 05. The proliferation and cytotoxicity of T cell were enhanced in mature DC pretreated group （ SI =6. 92, KRmax =73% , P 〈0. 05 ） , while they were distinctly decreased in TGFβ1-DC pretreated group （ SI = 1.13, KRmax = 6. 9% , P 〈 0. 05 ）. Nevertheless, there were no differences in three groups stimulated by T cell of SD rats. Conclusion TGF-β1 gene modified DC can induce tolerance of islet xenograft, probably through the anegy of T cell.