本文關(guān)鍵詞： B淋巴細(xì)胞刺激因子 重組TACI-Ig融合蛋白 T淋巴細(xì)胞 免疫治療 自身免疫病　出處：《安徽醫(yī)科大學(xué)學(xué)報(bào)》2016年07期 　論文類型：期刊論文

【摘要】：目的探討抗CD3抗體誘導(dǎo)小鼠T淋巴細(xì)胞增殖與活化的機(jī)制并觀察重組人TACI-Ig融合蛋白(rh TACI-Ig)對(duì)其的影響。方法免疫磁珠純化得到小鼠T淋巴細(xì)胞,用抗CD3抗體刺激,同時(shí)給予rh TACI-Ig、rh TNFR∶Fc或Ig G-Fc。[3H]-TdR參入法檢測(cè)T細(xì)胞增殖能力,流式細(xì)胞術(shù)檢測(cè)T細(xì)胞亞群比率,Western blot法檢測(cè)B淋巴細(xì)胞刺激因子、BAFF受體(BAFFR)和跨膜激活劑及鈣調(diào)親環(huán)素配體相互作用分子(TACI)兩個(gè)受體及IL-2受體(IL-2R)表達(dá)水平和NF-κB活性,采用小干擾RNA(siRNA)抑制T細(xì)胞BAFFR或TACI的表達(dá)。結(jié)果抗CD3抗體體外可促進(jìn)T細(xì)胞增殖與活化,BAFF、白細(xì)胞介素-2(IL-2)、γ-干擾素(IFN-γ)和轉(zhuǎn)化生長(zhǎng)因子-β(TGF-β)分泌,BAFFR、TACI、IL-2R表達(dá)升高和NF-κB活性增強(qiáng)(P0.05)。Rh TACI-Ig(0.1、1、10、100μg/ml)體外給藥可抑制抗CD3抗體誘導(dǎo)的T淋巴細(xì)胞增殖(P0.05);rh TACI-Ig(1、10、100μg/ml)可明顯降低抗CD3抗體誘導(dǎo)產(chǎn)生的細(xì)胞因子水平(P0.05,P0.01),顯著抑制CD4+CD69+T細(xì)胞、CD4+CD154+T細(xì)胞比率,提高CD4+CD62L+T細(xì)胞比率(P0.05,P0.01),且rh TACI-Ig(10、100μg/ml)能降低T細(xì)胞上BAFFR、TACI、IL-2受體的表達(dá),抑制NF-κB活性(P0.05)。沉默BAFFR或TACI對(duì)抗CD3抗體誘導(dǎo)的T細(xì)胞增殖有抑制作用(P0.01)。結(jié)論抗CD3抗體部分通過(guò)產(chǎn)生BAFF,激活BAFFR信號(hào)而促進(jìn)T細(xì)胞增殖與活化,rh TACI-Ig中和BAFF,抑制BAFF相關(guān)受體的表達(dá)和NF-κB活性,減少T細(xì)胞表達(dá)IL-2受體,阻止T細(xì)胞過(guò)度增殖與活化。
[Abstract]:Objective to investigate the mechanism of proliferation and activation of mouse T lymphocytes induced by anti CD3 antibody and to observe the recombinant human TACI-Ig fusion protein rh TACI-IgA. Methods Murine T lymphocytes were purified by immunomagnetic beads. CD3 antibody was used to stimulate rh TACI-IgA rh TNFR:Fc or Ig G-Fc. [3H] -TdR incorporation assay was used to detect the proliferation of T cells, and the ratio of T cell subsets to T lymphocyte subsets was detected by flow cytometry. Western blot assay was used to detect the B lymphocyte stimulating factor. The expression level and NF- 魏 B activity of BAFF receptor, transmembrane activator and calmodulin ligand interaction molecule (taii) and IL-2 receptor (IL-2R) were observed. The expression of BAFFR or TACI in T cells was inhibited by small interfering RNAs. Results Anti-BAFF antibody could promote the proliferation and activation of T cells in vitro. Interleukin-2, IFN- 緯) and transforming growth factor- 尾 (TGF- 尾) secrete BAFFRTACI. The expression of IL-2R increased and the activity of NF- 魏 B enhanced P0.05N. In vitro administration of 100 渭 g / ml inhibited the proliferation of T lymphocytes induced by anti CD3 antibody (P 0.05). Rh TACI-IgA (100 渭 g / ml) could significantly decrease the level of cytokines induced by anti CD3 antibodies (P0.05 and P0.01). The ratio of CD4 CD69 T cells to CD4 CD154 T cells was significantly inhibited, and the ratio of CD4 CD62L T cells was increased. Moreover, rh TACI-IgA 100 渭 g / ml decreased the expression of IL-2 receptor on T cells. Inhibition of NF- 魏 B activity (P0.05G). Silencing BAFFR or TACI inhibits the proliferation of T cells induced by CD3 antibody. Conclusion Antibody to CD3 is partly produced by BAFF. Activation of BAFFR signal could promote T cell proliferation and activation of rh TACI-Ig and BAFF, and inhibit the expression of BAFF related receptors and the activity of NF- 魏 B. Reduce T cell expression of IL-2 receptor and prevent T cell proliferation and activation.
【作者單位】： 安徽醫(yī)科大學(xué)臨床藥理研究所抗炎免疫藥物教育部重點(diǎn)實(shí)驗(yàn)室安徽抗炎免疫藥物協(xié)同創(chuàng)新中心;
【基金】：國(guó)家自然科學(xué)基金(編號(hào):81173075,81330081,81202541) 安徽省自然科學(xué)基金(編號(hào):1208085QH146) 安徽醫(yī)科大學(xué)青年拔尖人才支持計(jì)劃(2013) 第三批安徽醫(yī)科大學(xué)校級(jí)中青年學(xué)術(shù)技術(shù)帶頭人基金
【分類號(hào)】：R392
【正文快照】： 2016-04-06接收抗CD3抗體可以上調(diào)T淋巴細(xì)胞白細(xì)胞介素2受體(interleukine-2 receptor,IL-2R)表達(dá),誘導(dǎo)細(xì)胞增殖與活化[1]。活化的T細(xì)胞能分泌IL-1、IL-2、IL-6、IL-10和B淋巴細(xì)胞刺激因子(B lymphocyte stim-ulator,Bly S or BAFF)等多種細(xì)胞因子[2]。BAFF及APRIL水平的異常

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