首页 | 本学科首页   官方微博 | 高级检索  
     

T淋巴细胞内mTOR/S6途径在难治/复发再生障碍性贫血发病机制中的作用
引用本文:张翔,何广胜,吴德沛,孙爱宁,苗瞄,王秀丽,金正明,仇惠英,常伟荣. T淋巴细胞内mTOR/S6途径在难治/复发再生障碍性贫血发病机制中的作用[J]. 中华血液学杂志, 2009, 30(10). DOI: 10.3760/cma.j.issn.0253-2727.2009.10.003
作者姓名:张翔  何广胜  吴德沛  孙爱宁  苗瞄  王秀丽  金正明  仇惠英  常伟荣
作者单位:卫生部血栓与止血重点实验室,苏州大学附属第一医院、江苏省血液研究所,215006
基金项目:国家科技支撑计划,江苏省青年科技创新人才基金 
摘    要:目的 研究难治/复发再生障碍性贫血(AA)患者骨髓T淋巴细胞内雷帕霉素靶蛋白(mTOR)/核糖体蛋白S6途径活化情况,以及mTOR抑制剂雷帕霉素(RAPA)和CD28抗原阻断剂CTLA-4免疫球蛋白(CTLA-41g)对此途径的影响.方法 采集13例难治/复发AA、8例初治重型AA(SAA)以及1O例缺铁性贫血(IDA)患者(对照组)的骨髓标本,加入RAPA和CTLA-41g进行孵育,用流式细胞术检测加药前后每组患者CD3+T淋巴细胞胞质内磷酸化mTOR(p-mTOR)、磷酸化S6(P-S6)和干扰素-γ(IFN-γ)的表达水平,并分析其与疾病的关系.结果 ①难治/复发AA组患者骨髓CD3+T细胞胞内p-mTOR、P-S6及IFN-γ的表达水平较对照组显著升高(P值均<0.01).②初治SAA患者p-mTOR和p-S6的表达水平低于难治/复发AA组(P值均<0.01),而与对照组比较差异无统计学意义(P值均>0.05);初治组IFN-γ的表达水平明显高于对照组(P值均<0.01).③RAPA和CTLA-41g作用后,难治/复发AA患者p-mTOR、p-S6及IFN-γ的表达水平较用药前明显下降(P值均<0.01).结论 CD3+T淋巴细胞内mTOR/S6途径在难治/复发AA患者中活化.RAPA和CTLA-41g均可抑制难洽/复发AA患者体内mTOR/S6途径,并下调IFN-γ.CD28/mTOR/S6和IFN-γ途径参与难治/复发AA的免疫发病机制,并且对RAPA和CTLA-41g敏感,以CD28、mTOR为治疗靶点,临床应用RAPA和CTLA-4Ig治疗此类AA患者值得探索.

关 键 词:贫血  再生障碍性  T淋巴细胞  抗原  雷帕霉素靶蛋白  核糖体蛋白质S6  干扰素γ  CTLA-4免疫球蛋白

The role of intracellular signal pathway of mTOR/S6 in CD3+T lymphocytes of refractory/relapsed aplastic anemia patients
Abstract:Objective To explore the activation status of signal pathway of mTOR/S6 in bone marrow(BM) T lymphocytes of refractory/relapsed aplastic anemia patients(AA),and the effects of rapamycin (RAPA)and CTLA-4 immunoglobulin(CTLA-4 Ig)on this pathway.Methods BM was collected from 13refractory/relapsed AA patients,8 newly diagnosed severe AA(SAA)patients and 10 iron deficiency anemia (IDA)(as controls)patients,and cocultured with RAPA and CTLA-4 Ig.The expression of p-mTOR,p-S6 and Interferon γ(IFN-γ)in CD3+ T cells was measured by flow cytometry(FCM).Results ①The expression of p-mTOR,P-S6 and IFN-γ in CD3+ T cells in refractory/relapsed AA group were significantly higher than those in controls(P<0.01).②The expression of P-mTOR and p-S6 in T cels in newly diagnosed SAA group,Was similar to those in controls(P>0.05),but significantly lower than those in refractory/relapsed AA group(P<0.01).The expression level of IFN-γ in T cells were significantly higher than that in controls (P<0.01).③On exposure to RAPA,The levels of p-mTOR,p-S6 and IFN-γ in T cells in refractory/relapsed AA patients were significantly lower than those before the exposure(all P<0.05).And so were when exposed to CTLA-4 Ig(all P<0.01).Conclusion ①The mTOR/S6 signal pathway is activated in refractory/relapsed AA.②The expression of p-mTOR,p-S6 and IFN-γ in refractory/relapsed AA Can be suppressed by RAPA or CTLA-4 Ig.③The signal pathway of CD28/mTOR/S6/IFN-γ might take part in immune pathogenesis of refractory/relapsed AA.
Keywords:CD28
本文献已被 万方数据 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号