阻断转化生长因子β信号通路对树突细胞抗原递呈功能影响的研究

Effect of blocking the signal pathway of TGFβ on presenting antigen of dendritic cells

目的 研究阻断Smad信号是否能阻断树突细胞（DC）内的转化生长因子（TGF）β信号通路,及逆转TGF β对DC的免疫抑制作用.方法 用重组腺病毒载体将Smad7基因导入DC,并设对照组、DC＋TGF β组和转染空载体组DC,测定各组DC成熟相关表型的表达、刺激异基因淋巴细胞增殖的能力和诱导的细胞毒T淋巴细胞（CTL）杀伤活性.结果 在存在外源性TGFβ1的情况下,DC-Smad7组仍能高表达成熟相关黏附分子；刺激异基因淋巴细胞增殖的能力显著高于空载体组,差异有统计学意义（P＜0.01）；经小鼠Lewis肺癌细胞株L3-8可溶性抗原冲击致敏后免疫小鼠,得到的脾脏淋巴细胞在效靶比为25∶1、50∶1、100∶1时,CTL杀伤活性分别为21％、41％、59％,显著高于空载体组的15％、21％、34％,差异有统计学意义（均P＜0.01）.结论 阻断Smad信号可阻断TGFβ信号通路,逆转TGF

Objective To explore the dysfunction of dendritic cells （DC） related to TGFβ reversed after blocking the TGFβ signal pathway by recombinant adenovirus vector encoding for Smad7.Methods Smad7 by recombinant adenovirus vector was transfected into dendritic cells.Expression of immunologic phenotypes was detected by FCM,and CTL activity induced by DC was compared.Results The DC modified with Smad7 still expressed high adhesiveness factor related to maturation even if existing exogenous TGFβ1,which was significant statistically compared with DC transfected with control adenoviral vector （P 〈0.01）.Even if existing exogenous TGFβ1,the DC modified with Smad7 pulsed with soluble antigen associated with Lewis pulmonary carcinoma could still induce potent CTL activity against Lewis pulmonary carcinoma,which showed significant difference with DC-Ad-c （P 〈0.01）.Conclusion The inhibitory effects on function of DC of TGFβ may be reversed by blocking the Smad signal of TGFβ pathway