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GADD45β参与类风湿关节炎发病机制研究(2)-GADD45β介导类风关CD4+T细胞抗凋亡研究
2008年
在发现了GADD45β在类风湿关节炎(rheumatoid arthritis,RA)病灶局部组织细胞中、CD4+T细胞表达增高并参与介导IFN-γ产生的基础上,进一步探讨GADD45β参与RA的其他机制。用siRNA干扰人PBMC中GADD45β基因表达。Real-time PCR检测GADD45β和凋亡相关基因的表达格局。用RA患者滑膜液(RA synovial fluid,RA SF)刺激GADD45β基因敲除的健康人PBMC并用流式细胞仪检测细胞凋亡。结果RA患者的SFMC中T细胞凋亡减少。用SF刺激正常人PBMC时细胞凋亡减少。经siRNA干扰后PBMC中GADD45β的表达明显降低,同时细胞凋亡增加。同时检测与凋亡相关基因发现SF刺激后Bcl-2分子在凋亡的细胞中表达明显降低,而Fas-FasL、Bcl-2家族其他分子如Bcl-xl、Bax、Bim等变化不明显。GADD45β参与介导RA的炎症性T细胞凋亡,而Bcl-2分子参与了由GADD45β介导抗凋亡作用,而这一作用与RA患者滑膜液中炎症细胞能够长期存活并介导炎症可能有密切关系。
肖涟波欧阳桂林何东仪许荣何勇黄正解骏张秋玉杜芳沈佰华李宁丽王利
关键词:GADD45Β类风湿关节炎
Downregulation of CD4+CD25+ regulatory T cells may underlie enhanced Th1 immunity caused by immunization with activated autologous T cells被引量:6
2007年
Regulatory T cells (Treg) play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Thl responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4+CD25+ T cells from the immunized mice. Moreover, CD4+CD25+Foxp3+ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naive mice. Further analysis showed that the serum of immunized mice contains a high level ofanti-CD25 antibody (about 30 ng/ml, p〈0.01 vs controls). Consistent with a role ofanti-CD25 response in the downregulation of Treg, adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4+CD25+Foxp3+ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Thl response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.
Qi CaoLi WangFang DuHuiming ShengYan ZhangJuanjuan WuBaihua ShenTianweiShenJingwu ZhangDangsheng LiNingli Li
活性氧—适应性免疫应答的调节分子被引量:6
2008年
在免疫系统中,吞噬细胞是活性氧(ROS)的主要来源,淋巴细胞也能经线粒体和NADPH氧化酶途径生成活性氧。活性氧不仅参与固有免疫应答的抗感染防御过程,也参与适应性免疫应答,包括抗原提呈及淋巴细胞活化、增殖、分化和凋亡等各个环节。活性氧的具体效应与其存在的位置及其量的多少密切相关。过氧化氢可作为第二信使,参与胞内信号通路。本文综述近年来关于活性氧参与免疫应答的研究进展,旨在为氧化应激相关疾病的治疗提供新的思路。
张秋玉苏东辉李宁丽
关键词:活性氧免疫调节淋巴细胞第二信使
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