Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS
Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS
复制标题
DOI：
10.1189/jlb.1202598
复制
发表时间：
2003-05-01
影响因子：
5.5
通讯作者：
Uccelli, A
中科院分区：
文献类型：
--
作者：
Giunti, D;Borsellino, G;Uccelli, A
淋巴细胞跨越血脑屏障(BBB)的募集是由黏附分子和趋化因子介导的。活化标志物和趋化因子受体在定位于神经系统(NS)的T细胞上的表达可能有助于确定其功能状态。在包括多发性硬化在内的炎症性神经疾病(IND)患者的脑脊液(CSF)中，我们观察到共表达CXCR3和CCR5的T细胞以及具有CD45RO+CCR7+CD27+记忆表型的T细胞数量增加。CCR7+T细胞亚群共表达CXCR3和CCR5。我们还检测到，与外周血相比，脑脊液中产生干扰素-伽马的T细胞数量增加，主要但不只是CD45RO+CCR7-CD27-隔室。从IND患者和健康受试者的脑脊液建立的T辅助分子I(Th1)克隆类似地迁移到CXCL10、CXCL12和CCL5。神经炎症者脑脊液中CXCL10、CXCL12和CCL19均升高。这些发现表明，脑脊液中富含Th1极化的记忆T细胞，能够在遇到抗原时分化为效应细胞。这些细胞通过可诱导的趋化因子被招募到脑脊液中。因此，脑脊液代表了T细胞往返于NS的一个过渡站。
The recruitment of lymphocytes across the blood brain barrier (BBB) is mediated by adhesion molecules and chemokines. The expression of activation markers and of chemokine receptors on T cells homing to the nervous system (NS) may help define their functional state. In the cerebrospinal fluid (CSF) of subjects with inflammatory neurological diseases (IND), including multiple sclerosis, we observed an increased number of T cells coexpressing CXCR3 and CCR5 as well as T cells with a CD45RO+ CCR7+ CD27+ memory phenotype. A subset of CCR7+ T cells coexpressed CXCR3 and CCR5. We also detected an increased number of interferon-gamma-producing T cells in the CSF compared with peripheral blood, mostly but not exclusively in the CD45RO+ CCR7- CD27- compartment. T helper I (Th1) clones, established from the CSF of individuals with IND and from a healthy subject, similarly migrated to CXCL10, CXCL12, and CCL5. CXCL10, CXCL12, and CCL19 were increased in the CSF of individuals with neuroinflammation. These findings suggest that CSF is enriched in Th1-polarized memory T cells capable of differentiating into effector cells upon antigen encounter. These cells are recruited into the CSF by inducible chemokines. Thus, CSF represents a transitional station for T cells trafficking to and from the NS.