目的检测盘状红斑狼疮(DLE)患者外周T淋巴细胞CD70基因表达水平,并探讨CD70基因在DLE发病机理中的作用。方法 RT-PCR测定2014年1月至2015年6月在我院就诊的15例活动期、15例非活动期DLE患者和同期健康体检的15例健康人(对照组)外周血T...目的检测盘状红斑狼疮(DLE)患者外周T淋巴细胞CD70基因表达水平,并探讨CD70基因在DLE发病机理中的作用。方法 RT-PCR测定2014年1月至2015年6月在我院就诊的15例活动期、15例非活动期DLE患者和同期健康体检的15例健康人(对照组)外周血T淋巴细胞CD70 m RNA转录水平,流式细胞术检测各组样本中CD4+CD70+T/CD8+CD70+T的阳性率。结果活动期和非活动期DLE患者T淋巴细胞中的CD70 m RNA转录水平分别为(4.5±0.19)和(2.9±0.09),显著高于对照组的(1.9±0.11),差异均有显著统计学意义(P<0.01),且活动期DLE患者T淋巴细胞中的CD70 m RNA的转录水平明显高于非活动期DLE患者,差异具有统计学意义(P<0.05);活动期和非活动期DLE患者的外周血CD4+CD70+T淋巴细胞的阳性率分别为(18.82±1.22)%和(15.32±1.01)%,明显高于对照组的(14.63±0.41)%,差异均有统计学意义(P<0.05或P<0.01),且活动期DLE患者的阳性率显著高于非活动期DLE患者,统计有显著统计学意义(P<0.01);活动期和非活动期DLE患者T淋巴细胞中CD8+CD70+的阳性率与对照组比较,差异均无统计学意义(P>0.05)。结论 CD70基因的过度表达在DLE的发生发展中起着重要的作用,且CD70过度表达可作为检测DLE疾病患者的一个重要指标。展开更多
activation.Therefore,engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70.However,the T cell-intrinsic effect and function of human CD70 remain underexplored.Herein,we describe...activation.Therefore,engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70.However,the T cell-intrinsic effect and function of human CD70 remain underexplored.Herein,we describe that CD70 expression distinguishes proinflammatory CD4^(+)T lymphocytes that display an increased potential to migrate into the central nervous system(CNS).Upregulation of CD70 on CD4^(+)T lymphocytes is induced by TGF-β1 and TGF-β3,which promote a pathogenic phenotype.In addition,CD70 is associated with a TH1 and TH17 profile of lymphocytes and is important for T-bet and IFN-γexpression by both T helper subtypes.Moreover,adoptive transfer of CD70−/−CD4^(+)T lymphocytes induced less severe experimental autoimmune encephalomyelitis(EAE)disease than transfer of WT CD4^(+)T lymphocytes.CD70+CD4^(+)T lymphocytes are found in the CNS during acute autoimmune inflammation in humans and mice,highlighting CD70 as both an immune marker and an important costimulator of highly pathogenic proinflammatory TH1/TH17 lymphocytes infiltrating the CNS.展开更多
文摘目的检测盘状红斑狼疮(DLE)患者外周T淋巴细胞CD70基因表达水平,并探讨CD70基因在DLE发病机理中的作用。方法 RT-PCR测定2014年1月至2015年6月在我院就诊的15例活动期、15例非活动期DLE患者和同期健康体检的15例健康人(对照组)外周血T淋巴细胞CD70 m RNA转录水平,流式细胞术检测各组样本中CD4+CD70+T/CD8+CD70+T的阳性率。结果活动期和非活动期DLE患者T淋巴细胞中的CD70 m RNA转录水平分别为(4.5±0.19)和(2.9±0.09),显著高于对照组的(1.9±0.11),差异均有显著统计学意义(P<0.01),且活动期DLE患者T淋巴细胞中的CD70 m RNA的转录水平明显高于非活动期DLE患者,差异具有统计学意义(P<0.05);活动期和非活动期DLE患者的外周血CD4+CD70+T淋巴细胞的阳性率分别为(18.82±1.22)%和(15.32±1.01)%,明显高于对照组的(14.63±0.41)%,差异均有统计学意义(P<0.05或P<0.01),且活动期DLE患者的阳性率显著高于非活动期DLE患者,统计有显著统计学意义(P<0.01);活动期和非活动期DLE患者T淋巴细胞中CD8+CD70+的阳性率与对照组比较,差异均无统计学意义(P>0.05)。结论 CD70基因的过度表达在DLE的发生发展中起着重要的作用,且CD70过度表达可作为检测DLE疾病患者的一个重要指标。
基金T.D.holds a fellowship from the Fonds de Recherche du Québec-Santé(FRQS).L.T.holds scholarships from Universitéde Montréal and CRCHUM.E.P.holds a fellowship from the Multiple Sclerosis Society of Canada(MSSC)and the FRQS.S.Z.is supported by a fellowship from Biogen Canada.C.L.is supported by FRQS.A.P.holds the T1(senior)Canada Research Chair in Multiple Sclerosis.This work was funded by operating grants from the Canadian Institutes of Health Research(MOP 89885,PJI-153195)and from the MSSC(EGID 2382).We thank Jannie Borst for providing us with the CD70−/−mice.We thank Hartmut Wekerle for providing us with the TCR1640 mice.Special thanks to Magdalena Paterka and Volker Siffrin for providing the protocol for CD4+adoptive T cell transfer in RAG null mice.We would also like to thank the imaging platform,the pathology platform,and the flow cytometry platform from the CRCHUM for the excellent technical support and Alice M Roy and Elvia Gonzalez for their excellent technical animal support.
文摘activation.Therefore,engagement of the costimulatory CD27/CD70 pathway is solely dependent on upregulation of CD70.However,the T cell-intrinsic effect and function of human CD70 remain underexplored.Herein,we describe that CD70 expression distinguishes proinflammatory CD4^(+)T lymphocytes that display an increased potential to migrate into the central nervous system(CNS).Upregulation of CD70 on CD4^(+)T lymphocytes is induced by TGF-β1 and TGF-β3,which promote a pathogenic phenotype.In addition,CD70 is associated with a TH1 and TH17 profile of lymphocytes and is important for T-bet and IFN-γexpression by both T helper subtypes.Moreover,adoptive transfer of CD70−/−CD4^(+)T lymphocytes induced less severe experimental autoimmune encephalomyelitis(EAE)disease than transfer of WT CD4^(+)T lymphocytes.CD70+CD4^(+)T lymphocytes are found in the CNS during acute autoimmune inflammation in humans and mice,highlighting CD70 as both an immune marker and an important costimulator of highly pathogenic proinflammatory TH1/TH17 lymphocytes infiltrating the CNS.
