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

【摘要】：目的探討抗CD3抗體誘導小鼠T淋巴細胞增殖與活化的機制并觀察重組人TACI-Ig融合蛋白(rh TACI-Ig)對其的影響。方法免疫磁珠純化得到小鼠T淋巴細胞,用抗CD3抗體刺激,同時給予rh TACI-Ig、rh TNFR∶Fc或Ig G-Fc。[3H]-TdR參入法檢測T細胞增殖能力,流式細胞術(shù)檢測T細胞亞群比率,Western blot法檢測B淋巴細胞刺激因子、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)兩個受體及IL-2受體(IL-2R)表達水平和NF-κB活性,采用小干擾RNA(siRNA)抑制T細胞BAFFR或TACI的表達。結(jié)果抗CD3抗體體外可促進T細胞增殖與活化,BAFF、白細胞介素-2(IL-2)、γ-干擾素(IFN-γ)和轉(zhuǎn)化生長因子-β(TGF-β)分泌,BAFFR、TACI、IL-2R表達升高和NF-κB活性增強(P0.05)。Rh TACI-Ig(0.1、1、10、100μg/ml)體外給藥可抑制抗CD3抗體誘導的T淋巴細胞增殖(P0.05);rh TACI-Ig(1、10、100μg/ml)可明顯降低抗CD3抗體誘導產(chǎn)生的細胞因子水平(P0.05,P0.01),顯著抑制CD4+CD69+T細胞、CD4+CD154+T細胞比率,提高CD4+CD62L+T細胞比率(P0.05,P0.01),且rh TACI-Ig(10、100μg/ml)能降低T細胞上BAFFR、TACI、IL-2受體的表達,抑制NF-κB活性(P0.05)。沉默BAFFR或TACI對抗CD3抗體誘導的T細胞增殖有抑制作用(P0.01)。結(jié)論抗CD3抗體部分通過產(chǎn)生BAFF,激活BAFFR信號而促進T細胞增殖與活化,rh TACI-Ig中和BAFF,抑制BAFF相關(guān)受體的表達和NF-κB活性,減少T細胞表達IL-2受體,阻止T細胞過度增殖與活化。
[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)科大學臨床藥理研究所抗炎免疫藥物教育部重點實驗室安徽抗炎免疫藥物協(xié)同創(chuàng)新中心;
【基金】：國家自然科學基金(編號:81173075,81330081,81202541) 安徽省自然科學基金(編號:1208085QH146) 安徽醫(yī)科大學青年拔尖人才支持計劃(2013) 第三批安徽醫(yī)科大學校級中青年學術(shù)技術(shù)帶頭人基金
【分類號】：R392
【正文快照】： 2016-04-06接收抗CD3抗體可以上調(diào)T淋巴細胞白細胞介素2受體(interleukine-2 receptor,IL-2R)表達,誘導細胞增殖與活化[1]。活化的T細胞能分泌IL-1、IL-2、IL-6、IL-10和B淋巴細胞刺激因子(B lymphocyte stim-ulator,Bly S or BAFF)等多種細胞因子[2]。BAFF及APRIL水平的異常

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