【摘要】：Foxp3是叉頭樣轉(zhuǎn)錄因子(Forkhead transcription factor)P亞家族的新成員。目前研究證實(shí)該基因特異性表達(dá)于固有CD4~+CD25~+調(diào)節(jié)性T細(xì)胞,并在該細(xì)胞的發(fā)育和功能維持中起重要作用,是CD4~+CD25~+調(diào)節(jié)性T細(xì)胞特異性標(biāo)志物之一,并作為轉(zhuǎn)錄抑制因子參與免疫應(yīng)答的調(diào)控。Foxp3包含叉頭狀結(jié)構(gòu)域、C_2H_2鋅指結(jié)構(gòu)及亮氨酸拉鏈等保守序列,在與靶基因啟動(dòng)子和某些蛋白質(zhì)結(jié)合上起著重要作用。 近年來(lái),人們通過(guò)構(gòu)建Foxp3重組逆轉(zhuǎn)錄病毒、Foxp3轉(zhuǎn)基因模型等方法對(duì)該基因的作用機(jī)制及臨床應(yīng)用展開(kāi)了廣泛的研究。實(shí)驗(yàn)發(fā)現(xiàn)Foxp3的異位表達(dá)在體外可誘導(dǎo)與固有CD4~+CD25~+調(diào)節(jié)性T細(xì)胞表型及作用相似的調(diào)節(jié)性T細(xì)胞的產(chǎn)生;誘導(dǎo)產(chǎn)生的調(diào)節(jié)性T細(xì)胞在體內(nèi)可直接或間接抑制效應(yīng)性T淋巴細(xì)胞、B淋巴細(xì)胞及某些抗原提呈細(xì)胞(如樹(shù)突狀細(xì)胞)等的增殖、分化和免疫應(yīng)答,誘導(dǎo)體內(nèi)免疫耐受的產(chǎn)生,對(duì)治療某些自身免疫病及移植排斥反應(yīng)有一定效果;隨著研究的深入,該基因在腫瘤免疫的作用也越來(lái)越受到關(guān)注,有文獻(xiàn)報(bào)道在某些腫瘤組織及周?chē)馨徒Y(jié)等處發(fā)現(xiàn)Foxp3的表達(dá),為腫瘤逃逸機(jī)制的研究以及新型靶向制劑的開(kāi)發(fā)提供了新思路。 為更深入研究Foxp3的作用機(jī)制及誘導(dǎo)免疫耐受方面的應(yīng)用,本實(shí)驗(yàn)利用AdEasy~(TM)XL系統(tǒng)構(gòu)建攜帶Foxp3的重組腺病毒,并行初步鑒定。方法:從小鼠胸腺組織獲取約1.3kb大小的目的基因,克隆至穿梭載體pShuttle-IRES-hrGFP-1
[Abstract]:Foxp3 is a new member of (Forkhead transcription factor) P subfamily. At present, it has been confirmed that this gene is specifically expressed in inherent CD4~ CD25~ regulatory T cells and plays an important role in the development and functional maintenance of the cells. It is one of the specific markers of CD4~ CD25~ regulatory T cells. As a transcription suppressor, Foxp3 contains some conserved sequences, such as fork head domain, zinc finger structure of C_2H_2 and leucine zipper, which play an important role in binding to target gene promoter and some proteins. In recent years, the mechanism and clinical application of Foxp3 recombinant retrovirus and Foxp3 transgenic model have been extensively studied. It was found that the heterotopic expression of Foxp3 could induce the production of regulatory T cells similar to that of CD4~ CD25~ regulatory T cells in vitro. In vivo, regulatory T cells can directly or indirectly inhibit the proliferation, differentiation and immune response of effector T lymphocytes, B lymphocytes and some antigen-presenting cells (such as dendritic cells). The induction of immune tolerance in vivo is effective in the treatment of some autoimmune diseases and transplant rejection. With the development of the research, the role of the gene in tumor immunity has been paid more and more attention. It has been reported that the expression of Foxp3 is found in some tumor tissues and surrounding lymph nodes. It provides a new idea for the study of the mechanism of tumor escape and the development of new targeted preparations. In order to further study the mechanism of Foxp3 and its application in inducing immune tolerance, the recombinant adenovirus carrying Foxp3 was constructed by AdEasy~ (TM) XL system and identified. Methods: the target gene of about 1.3kb size was obtained from mouse thymus tissue and cloned into shuttle vector pShuttle-IRES-hrGFP-1.
【學(xué)位授予單位】：浙江大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2006
【分類(lèi)號(hào)】：R346

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 丁涵露,吳雄飛,高聞達(dá),賀偉峰,張曉容,吳軍;重組AdPD-L1腺病毒的構(gòu)建表達(dá)及鑒定[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2005年12期

2 陳祖兵,陶劍平,梁力建,劉曉平,胡文杰,李紹強(qiáng);腺病毒介導(dǎo)的T-bet基因轉(zhuǎn)染誘導(dǎo)Th1型淋巴細(xì)胞分化[J];中國(guó)病理生理雜志;2005年06期

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本文編號(hào)：2332931