CAJ | 학술논문

目的：探讨肝脏Kupffer细胞(KC)在脾内途径的肝脏靶向性基因治疗中的抗原提呈作用及可能机制。方法：以结肠癌肝转移小鼠为模型，以脾内移植GM-CSF基因修饰的胎肝细胞(FILC-GM)与低剂量IL-2、5-Fu腹腔注射作为基因治疗与化学免疫治疗联合应用方案。结果：荷瘤小鼠治疗后2 w，整个肝小叶KC数目均扩增；KC对99mTc-亚锡植酸钠吞噬功能明显增强；与KC抗原提呈功能和活化T细胞功能密切相关的共刺激分子CD40虽在对照组KC中有基础性表达，但在基因治疗联合化学免疫治疗组中，其表达水平皆有不同程度的上调；此外，联合治疗后KC体外能有效诱导同种T细胞增殖反应，细胞因子IL-12和IL-12的分泌水平亦升高，并且这些反应能被抗CD40L抗体所封闭。结论：脾内途径的肝脏靶向性基因治疗能有效提高KC的抗原提呈功能，CD40/CD40L分子在其中发挥了重要的共刺激作用。
목적：탐토간장Kupffer세포(KC)재비내도경적간장파향성기인치료중적항원제정작용급가능궤제。방법：이결장암간전이소서위모형，이비내이식GM-CSF기인수식적태간세포(FILC-GM)여저제량IL-2、5-Fu복강주사작위기인치료여화학면역치료연합응용방안。결과：하류소서치료후2 w，정개간소협KC수목균확증；KC대99mTc-아석식산납탄서공능명현증강；여KC항원제정공능화활화T세포공능밀절상관적공자격분자CD40수재대조조KC중유기출성표체，단재기인치료연합화학면역치료조중，기표체수평개유불동정도적상조；차외，연합치료후KC체외능유효유도동충T세포증식반응，세포인자IL-12화IL-12적분비수평역승고，병차저사반응능피항CD40L항체소봉폐。결론：비내도경적간장파향성기인치료능유효제고KC적항원제정공능，CD40/CD40L분자재기중발휘료중요적공자격작용。
The evidemce that Kupffer cells (KC) are capable of controlling metastatic growth in the liver is largely circumstantial.However,the ability of KC to function as antigen-presenting cells was not much studied. Thus,the aim of this study was to characterize the effect on the antigen-presenting function of Kupffer cells by intrasplenic transplantation of GM-CSF gene-modified fetal liver cells (FILC-GM)in combination with IL-2 and 5-Fu. Two weeks after the tumor-bearing mice was treated,strong increase in KC numbers and percentage of phagocytosis of 99mTc within the liver tissue were observed. At the same time, co-stimulator antigen CD40 expression on KC were determined by fluorescence-activated cell sorter( FACS) and found that its expression level was upregulated. In additioni, OVA-specific autogenetic T cells mixed lymphocyte reaction induced by KC have increased. Moreover, we observed that blocking CD40/CI40L interaction with anti-CD40L mAbs caused significantly inhibition of T cell proliferation response and inhibition of IL-2 and IL-12 production.These results indicated that intrasplenic transplantation of GM-CSF gene therapy in combination with immuno-chemotherapy could efficientiy activate the KC immunologic function, particularly its antigen-presenting function.