【摘要】 目的:探讨CD3/CD46共刺激通路对同种移植免疫反应的调控作用及其机制。方法:分离转人CD46的C57BL/6小鼠的脾脏淋巴细胞,采用MACS免疫磁珠分选CD4+T细胞,以阴性对照组作为对照,体外检测CD3、ConA、CD3/CD28、CD3/CD46、CD3/CD28/CD46共刺激对CD4+T细胞增殖的作用效果,并检测其细胞上清液中白细胞介素2(IL-2),γ-干扰素(γ-IFN),白细胞介素10(IL-10)和转化生长因子β(TGFβ-)的水平,并以BALB/c小鼠的脾细胞作为刺激细胞,以转人CD46的C57BL/6小鼠的淋巴细胞作为反应细胞进行同种混合淋巴细胞培养,MMT法检测淋巴细胞增殖活性。结果:与CD3组或阴性对照组相比,ConA、CD3/CD28、CD3/CD46和CD3/CD28/CD46共刺激后,CD4+T细胞均出现显著增殖反应(P<0.05),而且CD3/CD28/CD46共刺激组的增殖活性较CD3/CD28或CD3/CD46共刺激组显著增高(P<0.05)。CD3/CD28共刺激后,IL-2和γ-IFN水平较阴性对照组和CD3组显著升高(P<0.05),CD3/CD46共刺激后,IL-10和TGFβ-水平较阴性对照组、ConA组、CD3组和CD3/CD28共刺激组显著升高(P<0.05)。CD3/CD46共刺激后可以显著地抑制同种混合淋巴细胞的增殖反应(P<0.05)。结论:CD3/CD46共刺激通路可以诱导CD4+T细胞产生IL-10和TGFβ-,抑制同种移植免疫反应的发生。更多还原

【Abstract】 Objective:To investigate the allograft immune response regulated by CD3/CD46 costimulation as well as the mechanism involoved.Methods:CD4+T cells were isolated from spleens of human CD46-transgenic C57BL/6 mice by magnetic-activated cell sorting,CD4+ T cell proliferation was induced by anti-CD3,costimulations of anti-CD3/anti-CD28,anti-CD3/anti-CD46,or the monoclonal antibody panel against CD3/CD28/CD46,with ConA as the control.Producation of interleukin-2(IL-2),γ-interferon(γ-IFN),interleukin-10(IL10) and transforming growth factor-β(TGF-β) were detected in the supernants of different groups.Allo-MLR was examined by MTT colorimetry with Spleen cells from BALB/c mice as the stimulators and spleen cells of human CD46-transgenic C57BL/6 mice as respondors.Results:Compared with CD3 group or negative control group,ConA,CD3/CD28,CD3/CD46 and CD3/CD28/CD46 costimualtion all could significantly induce more proliferation(P<0.05),CD3/CD28/CD46 costimualtion significantly increased the proliferation compared with CD3/CD28 or CD3/CD46 consitmulation(P<0.05).IL-2 and γIFN level were significantly more increased in CD3/CD28 costimulation than in CD3 group or negative group(P<0.05),IL-10 and TGF-β levels were significant increased in CD3/CD46 costimulation compared with those of negative control,ConA,CD3 and CD3/CD28 group(P<0.05).CD3/CD46 constimulation significantly inhibited proliferation in mixed lymphocyte culture(P<0.05).Conclusion:CD3/CD46 constimulation induces IL-10 and TGF-β in CD4+T cells and inhibits allograft immune response.更多还原