本文關(guān)鍵詞：轉(zhuǎn)化生長(zhǎng)因子β1抑制T淋巴細(xì)胞功能及其相關(guān)機(jī)制的體外研究　出處：《安徽醫(yī)科大學(xué)》2005年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 轉(zhuǎn)化生長(zhǎng)因子β 免疫耐受 調(diào)節(jié)性T細(xì)胞 CTLA-4

【摘要】：目前治療器官移植排斥反應(yīng)的方法主要是應(yīng)用各種免疫抑制劑以及抗CD3、CD4等免疫活性細(xì)胞和活性分子的單克隆抗體,臨床效果較為滿意,但存在嚴(yán)重的全身性免疫抑制,已誘發(fā)感染和腫瘤發(fā)生。因此誘導(dǎo)機(jī)體產(chǎn)生特異性免疫耐受是克服移植排斥的理想途徑,始終是免疫學(xué)研究的熱點(diǎn)。近年來(lái),應(yīng)用細(xì)胞因子及其單克隆抗體治療器官移植排斥反應(yīng)受到廣泛的重視,其中以轉(zhuǎn)化生長(zhǎng)因子β(TGF-β)尤為引人關(guān)注。TGF-β是一種多向性的細(xì)胞因子,對(duì)免疫系統(tǒng)具有廣泛的抑制作用,極微量就具有很強(qiáng)的免疫抑制作用。一系列動(dòng)物體內(nèi)和體外實(shí)驗(yàn)證實(shí)TGF-β可以抑制T淋巴細(xì)胞增殖,并誘導(dǎo)出免疫耐受,本實(shí)驗(yàn)試圖通過(guò)觀察TGF-β1對(duì)人外周血T淋巴細(xì)胞增殖的影響,對(duì)其可能的作用機(jī)制進(jìn)行初步研究,以期為日后臨床應(yīng)用的可能性提供實(shí)驗(yàn)依據(jù)。 目的 通過(guò)TGF-β對(duì)T細(xì)胞的抗增殖作用及其可能機(jī)制的研究,試圖為移植排斥反應(yīng)的治療提供一條新的途徑。本實(shí)驗(yàn)觀察TGF-β1在混合淋巴細(xì)胞反應(yīng)中對(duì)T細(xì)胞增殖的影響,并進(jìn)一步探討其作用機(jī)理。 方法 分離不同個(gè)體健康成年人外周血淋巴細(xì)胞進(jìn)行初次及再次混合淋巴細(xì)胞培養(yǎng)(MLC),設(shè)TGF-β1組和對(duì)照組,在不同時(shí)間點(diǎn)以MTT法檢測(cè)T細(xì)胞增殖率,用乳酸脫氫酶法測(cè)定細(xì)胞毒活性,以ELISA法測(cè)定培養(yǎng)上清中IFN-γ及IL-2水平,并用流式細(xì)胞儀檢測(cè)T細(xì)胞表面CD4CD25及CTLA4抗原表達(dá)。 結(jié)果 初次及再次MLC均顯示,TGF-β1組細(xì)胞增殖反應(yīng)明顯低于對(duì)照組,CTL的細(xì)胞毒性受到明顯抑制,初次MLC中TGF-β1組培養(yǎng)上清內(nèi)IFN-γ及IL-2水平明顯低于對(duì)照組。初次MLC 5天后反應(yīng)體系中CD4CD25T細(xì)胞比例及CTLA4抗原表達(dá)明顯高于對(duì)照組。在再次MLC中,TGF-β1作用過(guò)的反應(yīng)細(xì)胞對(duì)來(lái)自第三者的刺激細(xì)胞無(wú)反應(yīng)。 結(jié)論 ① TGF-β1在人外周血混合淋巴細(xì)胞培養(yǎng)中對(duì)T細(xì)胞增殖有顯著抑
[Abstract]:At present, the main treatment for organ transplantation rejection is to use a variety of immunosuppressants and monoclonal antibodies against immunoreactive cells and active molecules such as CD3P4. The clinical results are satisfactory. But there is serious systemic immunosuppression, which has induced infection and tumorigenesis. Therefore, inducing specific immune tolerance is an ideal way to overcome transplant rejection and has always been a hot topic in immunology. The application of cytokines and their monoclonal antibodies in the treatment of organ transplantation rejection has received extensive attention. Transforming growth factor 尾 (TGF- 尾) is a multidirectional cytokine, which has a wide range of inhibitory effects on the immune system. A series of animal experiments in vivo and in vitro confirmed that TGF- 尾 could inhibit the proliferation of T lymphocytes and induce immune tolerance. By observing the effect of TGF- 尾 1 on the proliferation of human peripheral blood T lymphocytes, the possible mechanism of TGF- 尾 1 was studied in order to provide experimental evidence for the possibility of clinical application in the future. Objective to study the antiproliferative effect of TGF- 尾 on T cells and its possible mechanism. In this study, we observed the effect of TGF- 尾 1 on the proliferation of T cells in mixed lymphocyte reaction, and further discussed the mechanism of TGF- 尾 1 on T cell proliferation. Methods Peripheral blood lymphocytes from healthy adults were isolated and cultured for the first time and again. TGF- 尾 1 group and control group were divided into two groups: TGF- 尾 1 group and control group. At different time points, T cell proliferation rate was detected by MTT method, cytotoxic activity was measured by lactate dehydrogenase assay, IFN- 緯 and IL-2 levels in culture supernatant were measured by ELISA method. The expression of CD4CD25 and CTLA4 on T cells was detected by flow cytometry. Results MLC showed that the cytotoxicity of TGF- 尾 1 group was significantly lower than that of control group. The levels of IFN- 緯 and IL-2 in the culture supernatant of the primary MLC group were significantly lower than those in the control group. After 5 days, the proportion of CD4CD25T cells and the expression of CTLA4 antigen in the reaction system were significantly higher than those in the control group. TGF- 尾 _ 1-尾 _ (1)-activated response cells did not respond to stimulation cells from third parties. Conclusion 1 TGF- 尾 1 has a significant inhibitory effect on T cell proliferation in human peripheral blood mixed lymphocyte culture.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類號(hào)】：R392.4

【引證文獻(xiàn)】

相關(guān)期刊論文 前1條

1 張蕊;高雪麗;李博韜;鄭世民;;傳染性法氏囊病毒感染SPF雛雞哈德?tīng)栂俸兔つc扁桃體TGF-β1 mRNA表達(dá)變化[J];中國(guó)家禽;2013年09期

相關(guān)碩士學(xué)位論文 前3條

1 陳威;H5N1流感病毒感染雛鴨免疫器官TGF-β1mRNA表達(dá)與免疫功能抑制[D];東北農(nóng)業(yè)大學(xué);2008年

2 鄭艷生;IBDV感染雛雞外周血免疫功能及TGF-β1 mRNA表達(dá)變化[D];東北農(nóng)業(yè)大學(xué);2012年

3 張蕊;IBDV感染SPF雛雞局部黏膜TGF_(β1) mRNA表達(dá)及免疫功能的變化[D];東北農(nóng)業(yè)大學(xué);2013年

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本文編號(hào)：1437282