Frisullo Giovanni, Angelucci Francesco, Caggiula Marcella, Nociti Viviana, Iorio Raffaele, Patanella Agata Katia, Sancricca Cristina, Mirabella Massimiliano, Tonali Pietro Attilio, Batocchi Anna Paola
Institute of Neurology, Department of Neuroscience, Catholic University, Rome, Italy.
J Neurosci Res. 2006 Oct;84(5):1027-36. doi: 10.1002/jnr.20995.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, and it is considered to be a T helper 1 (Th1) cell-mediated autoimmune disease. T-bet has been identified as a key transcription factor for the development of Th1 cells and the induction of interferon (IFN)-gamma production. T-bet is induced during T-cell activation by the IFN-gamma signal transducer and activator of transcription (STAT)-1 signalling pathway. In this study we found an up-regulation of T-bet and pSTAT1 in peripheral blood CD4+ and CD8+ T cells and monocytes from relapsing-remitting MS patients in relapse compared with patients in remission and with healthy subjects. The increased expression of pSTAT1 strongly correlated with T-bet expression in CD4+ and CD8+ cells and monocytes from patients in relapse and was associated with an increased production of IFN-gamma by peripheral blood mononuclear cells (PBMCs). pSTAT3 was also up-regulated in CD4+ and CD8+ cells and monocytes from patients in relapse and was associated with an increased production of interleukin (IL)-10 but not of IL-6. pSTAT1, pSTAT3, and T-bet expression strongly correlated with Gd-DTPA-enhanced lesions on brain and spinal cord magnetic resonance imaging. Our data show for the first time that there is an up-regulation of type 1 immunity-correlated transcription factors such as STAT1 and T-bet in peripheral blood subpopulations of MS patients in the active phase of disease. The evaluation of T-bet and pSTAT1 expression in peripheral blood CD4+, CD8+ T cells and monocytes could be used as a marker of disease activity in relapsing-remitting MS.
多发性硬化症（MS）是一种中枢神经系统的慢性炎性脱髓鞘疾病，被认为是一种由辅助性T细胞1（Th1）介导的自身免疫性疾病。T-bet已被确定为Th1细胞发育和干扰素（IFN）-γ产生诱导的关键转录因子。T-bet在T细胞活化过程中由IFN-γ信号转导和转录激活因子（STAT）-1信号通路诱导产生。在本研究中，我们发现复发缓解型MS患者复发期外周血CD4+和CD8+ T细胞及单核细胞中T-bet和磷酸化STAT1（pSTAT1）上调，而缓解期患者和健康受试者则无此现象。复发期患者CD4+和CD8+细胞及单核细胞中pSTAT1表达增加与T-bet表达密切相关，并与外周血单个核细胞（PBMC）产生IFN-γ增加有关。复发期患者CD4+和CD8+细胞及单核细胞中pSTAT3也上调，并与白细胞介素（IL）-10产生增加有关，但与IL-6产生增加无关。pSTAT1、pSTAT3和T-bet表达与脑和脊髓磁共振成像上的钆喷酸葡胺（Gd-DTPA）增强病灶密切相关。我们的数据首次表明，在疾病活动期MS患者的外周血亚群中，1型免疫相关转录因子如STAT1和T-bet上调。评估外周血CD4+、CD8+ T细胞和单核细胞中T-bet和pSTAT1表达可作为复发缓解型MS疾病活动的标志物。
