Putheti P, Morris M, Stawiarz L, Teleshova N, Kivisäkk P, Pashenkov M, Kouwenhoven M, Wiberg M K, Bronge L, Huang Y-M, Söderström M, Hillert J, Link H
Division of Neuroimmunology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
Eur J Neurol. 2003 Sep;10(5):529-35. doi: 10.1046/j.1468-1331.2003.00638.x.
Magnetic resonance imaging (MRI) remains the most valuable tool for monitoring disease activity and progression in patients with multiple sclerosis (MS), a chronic demyelinating disease of the central nervous system (CNS) with presumably autoimmune etiology. Chemokine receptors have been implicated in MS as key molecules directing inflammatory cells into the CNS. Regulatory (CD4+CD25+) T cells (Tr cells) are important in suppressing autoimmunity, and their absolute or functional deficit could be expected in MS. In the present study, venous blood was obtained from MS patients concurrent with MRI examination of the brain, and expression of chemokine receptors CCR1, CCR2, CCR5, CXCR3 and CXCR4 by CD4 T cells and monocytes, proportions of Tr cells, as well as expression of CD45RO, CD95, CTLA-4, HLA-DR and interleukin (IL)-10 by Tr cells and non-Tr (CD25-) CD4 T cells was analyzed by flow cytometry. Surface expression of CXCR3 by CD4 T cells was downregulated in the group of patients with high lesion load (LL) on T2-weighted images and gadolinium (Gd)-enhancing lesions on T1-weighted images, compared to the group with high LL and no Gd-enhancing lesions, and to the group with low LL, suggesting internalization of CXCR3 due to the release of its chemokine ligand (IP-10/CXCL10) from active MS lesions. Proportions of Tr cells amongst all CD4 T cells, and expression of IL-10 by Tr cells were increased in the patients with high LL and Gd-enhancing lesions. These results suggest that there is correlation between MRI parameters, chemokine receptor expression and the status of circulating Tr cells in MS, but further studies need to discriminate between pathogenetically relevant and bystander phenomena.
磁共振成像（MRI）仍然是监测多发性硬化症（MS）患者疾病活动和进展的最有价值工具。MS是一种中枢神经系统（CNS）的慢性脱髓鞘疾病，病因可能为自身免疫性。趋化因子受体被认为是MS中引导炎症细胞进入CNS的关键分子。调节性（CD4+CD25+）T细胞（Tr细胞）在抑制自身免疫中起重要作用，预计在MS患者中会出现其绝对数量或功能缺陷。在本研究中，在对脑部进行MRI检查的同时采集了MS患者的静脉血，通过流式细胞术分析了CD4 T细胞和单核细胞上趋化因子受体CCR1、CCR2、CCR5、CXCR3和CXCR4的表达、Tr细胞的比例，以及Tr细胞和非Tr（CD25-）CD4 T细胞上CD45RO、CD95、CTLA-4、HLA-DR和白细胞介素（IL）-10的表达。与高病灶负荷（LL）且无钆（Gd）增强病灶的组以及低LL组相比，在T2加权图像上有高LL且在T1加权图像上有Gd增强病灶的患者组中，CD4 T细胞上CXCR3的表面表达下调，这表明由于活性MS病灶释放其趋化因子配体（IP-10/CXCL10）导致CXCR3内化。在高LL且有Gd增强病灶的患者中，所有CD4 T细胞中Tr细胞的比例以及Tr细胞中IL-10的表达增加。这些结果表明，MS患者的MRI参数、趋化因子受体表达与循环Tr细胞状态之间存在相关性，但需要进一步研究以区分致病相关现象和旁观者现象。
