本文關(guān)鍵詞：輔助抑制分子在誘導(dǎo)口服免疫耐受中的增強(qiáng)效果　出處：《延邊大學(xué)》2007年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： oral-tolerance B7-H1 B7-H4 同種異型抗原(allogeneic antigen)

【摘要】： 背景：B7-H1是輔助免疫調(diào)節(jié)分子B7大家族中的一個(gè)，B7家族被熟知為對(duì)周圍系統(tǒng)免疫調(diào)節(jié)起著重要作用。最近，新發(fā)現(xiàn)B7家族的新成員—B7-H4，發(fā)現(xiàn)其對(duì)腫瘤細(xì)胞特異性T細(xì)胞有抑制作用。同時(shí)通過(guò)口腔投入抗原的研究中發(fā)現(xiàn)：機(jī)體再次遭遇此同種抗原時(shí)免疫力明顯下降。前者是免疫調(diào)節(jié)中起重要作用的因子，后者在動(dòng)物實(shí)驗(yàn)和臨床治療中易行且被廣泛應(yīng)用。對(duì)于移植排斥反應(yīng)，自身免疫性疾病等需要通過(guò)降低機(jī)體免疫力來(lái)治療的疾病中此類聯(lián)合應(yīng)用治療手段已經(jīng)成為降低免疫治療領(lǐng)域中的熱點(diǎn)。 目的：1)用樹(shù)枝狀細(xì)胞株—DC2.4誘導(dǎo)對(duì)同種抗原的口服免疫耐受；2)檢測(cè)B7-H1，B7-H4在誘導(dǎo)口服免疫寬容中的作用；3)檢測(cè)有免疫調(diào)節(jié)作用的細(xì)胞變化；探討它們?cè)谡{(diào)節(jié)機(jī)體免疫中的作用和關(guān)系。 方法：1)給BALB／C(H-2d)小鼠每天喂食樹(shù)枝狀細(xì)胞株—DC2.4(H-2b)，誘導(dǎo)對(duì)同種抗原的免疫耐受；2)通過(guò)靜脈動(dòng)力進(jìn)樣(hydrodynamic injection)B7-El或B7-H4 DNA，并利用酶聯(lián)接免疫吸附劑測(cè)定(Enzyme-Linked Immunosorbnent Assay ELISA)檢測(cè)其在血液中分泌的B7-H1或B7-H4蛋白質(zhì)的量；3)通過(guò)檢測(cè)延遲過(guò)敏反應(yīng)(DTH)和單向混合淋巴細(xì)胞反應(yīng)(mixed lymphocyte reaction，MLR)來(lái)檢測(cè)機(jī)體免疫力的變化；4)分離脾細(xì)胞，腸系膜淋巴細(xì)胞等免疫細(xì)胞，進(jìn)行流式染色，檢測(cè)細(xì)胞群的變化；5)采用逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(RT-PCR)，，比較B7-H1，B7-H4注射組和對(duì)照組中分別分離免疫細(xì)胞，并擴(kuò)增免疫細(xì)胞中的FoxP3基因，并以核基因組的GAPDH作為定量標(biāo)準(zhǔn)物，比較FoxP3基因的表達(dá)差異。 結(jié)果：1)給BALB／C(H-2d)小鼠每天喂食樹(shù)枝狀細(xì)胞株—DC2.4(H-2b)，誘導(dǎo)出了對(duì)同種異型抗原的免疫耐受(P＜0.01)；2)喂食DC2.4同時(shí)注射B7-H1或B7-H4 DNA的群體比較對(duì)照組延遲過(guò)敏反應(yīng)明顯降低(P＜0.05)，從注射B7-H1或B7-H4 DNA的群體中分離的免疫細(xì)胞做的單向混合淋巴細(xì)胞反應(yīng)明顯降低(P＜0.05)；3)IFN-γ，IL-5，TNF-α表達(dá)水平明顯減低(P＜0.05)；4)CD4+CD25+FoxP3+免疫調(diào)節(jié)T細(xì)胞在CD4+細(xì)胞群中的百分比明顯增高(P＜0.05)；5)CD4+細(xì)胞中FoxP3基因的表達(dá)對(duì)比比較組明顯增高(P＜0.05)。 結(jié)論：1)給予BALB／C小鼠口腔投入樹(shù)枝狀細(xì)胞株—DC2.4，可誘導(dǎo)對(duì)同種抗原的口服免疫寬容。2)B7-H1，B7-H4在誘導(dǎo)口服免疫寬容中有增強(qiáng)作用。3)用DC2.4誘導(dǎo)免疫寬容并注射B7-H1，B7-H4 plasmid DNA的群體中分離的脾細(xì)胞和腸系膜淋巴細(xì)胞的增殖能力比較對(duì)比組中分離的細(xì)胞明顯下降。4)B7-H1，B7-H4在誘導(dǎo)口服免疫寬容中的增強(qiáng)作用可能與其對(duì)Th1和Th2細(xì)胞因子的分泌減少和產(chǎn)生較多的CD4+CD25+FoxP3+免疫調(diào)節(jié)T細(xì)胞有關(guān)。
[Abstract]:Background: B7-H1 is a member of the costimulatory immunomodulator B7 family, which is known to play an important role in peripheral immune regulation. A new member of the B7 family, B7-H4, was discovered. It was found that it had inhibitory effect on tumor cell specific T cells. At the same time, it was found in the study of oral antigens that:. When the body encounters this same antigen again, the immunity is obviously decreased. The former is an important factor in immune regulation. The latter is easy and widely used in animal experiments and clinical treatment. Autoimmune diseases and other diseases which need to be treated by reducing immunity have become a hot spot in the field of immunoreduction. Objective: to induce oral immune tolerance to alloantigen by dendritic cell line DC2.4. 2) to detect the role of B7-H1B7-H4 in inducing oral immune tolerance; 3) the changes of immunomodulatory cells were detected. To explore their role and relationship in the regulation of body immunity. Methods BALB / CnH-2d) mice were fed with dendritic cell line -DC2.4H-2b1 every day to induce immune tolerance to the same antigen. 2) hydrodynamic injection)B7-El or B7-H4 DNA were injected by intravenous dynamic sampling. Enzyme-Linked Immunosorbnent Assay ELISAA was determined by enzyme-linked immunosorbent assay. The amount of B7-H1 or B7-H4 protein secreted in blood was measured. 3) delayed hypersensitivity (DTH) and unidirectional mixed lymphocyte reaction (unidirectional mixed lymphocyte reaction) were detected. MLR was used to detect the changes of immunity. 4) spleen cells, mesenteric lymphocytes and other immune cells were isolated, and the changes of cell group were detected by flow cytometry. 5) Immunocytes were isolated and amplified by reverse transcription-polymerase chain reaction (RT-PCR) in B7-H1B7-H4 injection group and control group, respectively. GAPDH of nuclear genome was used as quantitative standard to compare the difference of FoxP3 gene expression. Results (1) BALB / CnH-2d) mice were fed with dendritic cell line -DC2.4 ~ (H-2b) per day, and the immune tolerance to allogenic antigen was induced (P < 0.01). 2) the delayed anaphylaxis was significantly lower in the group fed with DC2.4 and injected with B7-H1 or B7-H4 DNA than that in the control group (P < 0.05). The unidirectional mixed lymphocyte reaction of immune cells isolated from the population injected with B7-H1 or B7-H4 DNA decreased significantly (P < 0.05). 3The expression of IL-5 TNF- 偽 in IFN- 緯 was significantly decreased (P < 0.05). 4the percentage of CD4 CD25 FoxP3 immunomodulatory T cells in CD4 cell group was significantly increased (P < 0.05). The expression of FoxP3 gene in CD4 cells was significantly higher than that in control group (P < 0.05). Conclusion the oral administration of BALB/C mouse oral dendritic cell line -DC2.4can induce oral immunity tolerance to alloantigen. B7-H4 has an enhanced effect in inducing oral immune tolerance. 3) DC2.4 was used to induce immune tolerance and B7-H1 was injected. The proliferation ability of spleen cells and mesenteric lymphocytes isolated from B7-H4 plasmid DNA group was significantly lower than that of control group. The role of B7-H4 in inducing oral immune tolerance may be related to the decrease of Th1 and Th2 cytokines secretion and the production of CD4 CD25 FoxP3. Immune regulatory T cells are involved.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2007
【分類號(hào)】：R392

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