Kivisäkk P, Trebst C, Liu Z, Tucky B H, Sørensen T L, Rudick R A, Mack M, Ransohoff R M
Department of Neurosciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Clin Exp Immunol. 2002 Sep;129(3):510-8. doi: 10.1046/j.1365-2249.2002.01947.x.
It is believed that chemokines and their receptors are involved in trafficking of T-cells to the central nervous system (CNS). The aim of the current study was to define the expression on cerebrospinal fluid (CSF) T-cells of six chemokine receptors associated with trafficking to sites of inflammation. Flow cytometry was used to detect chemokine receptor expression. We observed that CD3+T-cells in the CSF express a restricted array of inflammatory chemokine receptors, specifically CXCR3, CCR5 and CCR6, but little CCR1-3. This repertoire was independent of the presence of CNS inflammation, since comparable findings were obtained in patients with multiple sclerosis (MS) and individuals with non-inflammatory neurological diseases. The enrichment of CCR5+T-cells in the CSF could largely be explained by higher frequency of CD4+/CD45RO+T-cells in this compartment. In contrast, CD4+/CD45RO+T-cells expressing CXCR3 were significantly enriched in CSF as compared with blood. Similar levels of CCR6+/CD3+T-cells were observed in blood and CSF, while levels of CCR2+/CD3+T-cells were lower in CSF than in blood. The CSF was virtually devoid of CCR5+/CXCR3- T-cells, suggesting that the expression of CCR5 alone is not sufficient for the trafficking of CD3+T-cells to the CSF. We hypothesize that CXCR3 is the principal inflammatory chemokine receptor involved in intrathecal accumulation of T-cells in MS. Through interactions with its ligands, CXCR3 is proposed to mediate retention of T-cells in the inflamed CNS.
据信趋化因子及其受体参与了T细胞向中枢神经系统（CNS）的转运。本研究的目的是确定与炎症部位转运相关的六种趋化因子受体在脑脊液（CSF）T细胞上的表达情况。采用流式细胞术检测趋化因子受体的表达。我们观察到CSF中的CD3⁺T细胞表达一系列有限的炎性趋化因子受体，特别是CXCR3、CCR5和CCR6，但CCR1 - 3表达较少。这种表达谱与CNS炎症的存在无关，因为在多发性硬化症（MS）患者和非炎性神经疾病患者中获得了类似的结果。CSF中CCR5⁺T细胞的富集在很大程度上可以用该亚群中CD4⁺/CD45RO⁺T细胞的较高频率来解释。相比之下，与血液相比，表达CXCR3的CD4⁺/CD45RO⁺T细胞在CSF中显著富集。在血液和CSF中观察到CCR6⁺/CD3⁺T细胞水平相似，而CSF中CCR2⁺/CD3⁺T细胞水平低于血液。CSF中几乎没有CCR5⁺/CXCR3⁻T细胞，这表明仅CCR5的表达不足以使CD3⁺T细胞转运至CSF。我们假设CXCR3是参与MS中T细胞鞘内积聚的主要炎性趋化因子受体。通过与其配体的相互作用，CXCR3被认为介导T细胞在炎症CNS中的滞留。
