TGF-β1基因修饰的未成熟树突状细胞对小肠移植大鼠外周血及移植肠浸润T细胞的影响

Effects of Immature Dendritic Cell Transfected by TGF-β1 Recombinated Adenovirus Vector on T Lymphocyte in Peripheral Blood and Allograft after Small Bowel Transplantation in Rat

目的探讨经转化生长因子-β1(TGF-β1)基因修饰的未成熟树突状细胞(imDC)预处理大鼠小肠移植受体后的外周血及移植肠浸润T细胞的变化及意义。方法选用近交系F344/N和BN大鼠建立全小肠异位移植模型,实验分4组(每组24只):同基因移植组(BN-BN组)、异基因移植组(F344/N-BN组)、异基因移植+TGF-β1基因转染imDC组(F344/N-BN+TGF-β1组)和异基因移植+TGF-β1基因转染imDC+FK506组(F344/N-BN+TGF-β1+FK506组)。各组大鼠分别于术后3、5、7d各处死6只,获取大鼠静脉血和移植肠。应用免疫组化SABC法检测受体鼠外周血及移植肠CD4+、CD8+、CD25+细胞和IL-4的表达。同时行移植肠组织病理学检查并观察大鼠生存情况。结果TGF-β1修饰的DC细胞能显著抑制外周血及移植肠浸润淋巴细胞CD4+、CD8+及CD25+的表达,并提高IL-4的表达;显著延长受体大鼠的生存时间,但移植肠仍有排斥反应的病理组织学征象。结论TGF-β1修饰的DC通过影响受体外周血及移植肠浸润T细胞对大鼠小肠移植发挥免疫抑制作用。

Objective To investigate the effect of immature dendritic cell （imDC）transfected by TGF-β1 recombinated adenovirus vector on T lymphocyte in peripheral blood and allograft after small bowel transplantation in rat. Methods Heterotopic small bowel transplantations were performed with 72 F344/N rats and 24 BN rats as donors and 96 BN rats as recipients. The recipients were divided into four groups randomly （n= 24） ： isograft group （BN-BN group）, allograft group （F344/N-BN group）, TGF-β1 allograft group （F344/N-BN＋TGF-β1 group）, and FK506-TGF-β1 allograft group （F344/N-BN＋TGF-β1＋FK506 group）. Six rats in each of the group on day 3, 5, and 7 were killed respectively and their peripheral blood and the whole graft jejunum were taken for further examinations. Immunohistochemistry SABC was used to analyze the expressions of CD4^＋, CD8^＋, CD25^＋ and IL-4 in lymphocytes in peripheral blood and allograft. The histopathologic signs of rejection in grafts and the recipients survival were also to be observed. Results ImDC transfected by TGF-β1 recombinated adenovirus vector significantly suppressed the expressions of CD4^＋, CD8^＋ and CD25^＋, but increased the expression of IL-4 in lymphocytes in peripheral blood and infiltrated allograft. It remarkably extended survival time of recipient, but the histopathologic signs of rejection still existed. Conclusion ImDC transfected by TGF-β1 recombinated adenovirus vector could take an inhibitory effect on allograft rejection by affecting T lymphocyte in peripheral blood and T lymphocyte infiltrated allograft.