Blauth Kevin, Zhang Xin, Chopra Manisha, Rogan Sarah, Markovic-Plese Silva
Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, USA.
Department of Neurology, University of North Carolina at Chapel Hill, NC 27599, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC 27599, USA.
Clin Immunol. 2015 Apr;157(2):121-32. doi: 10.1016/j.clim.2015.01.001. Epub 2015 Jan 14.
Fractalkine (CX3CL1) levels are increased in the cerebrospinal fluid (CSF) of patients with clinically isolated syndrome (CIS), as well as in the CSF and serum samples from patients with relapsing-remitting multiple sclerosis (RRMS). A higher percentage of circulating CD4(+) T-cells expressed its surface receptor (CX3CR1) and intracellular adhesion molecule (ICAM-1) in RRMS patients in comparison to healthy controls (HCs). The CX3CR1(+)ICAM-1(+)CD4(+) T-cells are enriched in the CSF of the RRMS patients. In vitro migration studies revealed that CD4(+) T-cells, which migrated toward a CX3CL1 gradient, expressed higher levels of ICAM-1 than non-migrating cells. CX3CL1 significantly increased IFN-γ and TNF-α gene expression and IFN-γ secretion by CD4(+) T-cells derived from the RRMS patients. CX3CL1 upregulated ICAM-1 expression on the surface of RRMS patient-derived but not HC-derived CD4(+) T-cells. Thus, CX3CL1 induces recruitment of CX3CR1(+)ICAM-1(+)CD4(+) T-cells into the central nervous system (CNS) during the early inflammatory response in MS.
在临床孤立综合征（CIS）患者的脑脊液（CSF）中，以及复发缓解型多发性硬化症（RRMS）患者的脑脊液和血清样本中，趋化因子（CX3CL1）水平升高。与健康对照（HC）相比，RRMS患者中循环CD4(+) T细胞表达其表面受体（CX3CR1）和细胞间黏附分子（ICAM-1）的比例更高。CX3CR1(+)ICAM-1(+)CD4(+) T细胞在RRMS患者的脑脊液中富集。体外迁移研究表明，向CX3CL1梯度迁移的CD4(+) T细胞比未迁移的细胞表达更高水平的ICAM-1。CX3CL1显著增加RRMS患者来源的CD4(+) T细胞的IFN-γ和TNF-α基因表达以及IFN-γ分泌。CX3CL1上调RRMS患者来源而非HC来源的CD4(+) T细胞表面的ICAM-1表达。因此，在MS的早期炎症反应中，CX3CL1诱导CX3CR1(+)ICAM-1(+)CD4(+) T细胞募集到中枢神经系统（CNS）。
