Fife B T, Kennedy K J, Paniagua M C, Lukacs N W, Kunkel S L, Luster A D, Karpus W J
Department of Pathology, Immunobiology Center, Robert H. Lurie Cancer Center, and Institute for Neuroscience, Northwestern University Medical School, Chicago, IL 60611, USA.
J Immunol. 2001 Jun 15;166(12):7617-24. doi: 10.4049/jimmunol.166.12.7617.
Experimental autoimmune encephalomyelitis (EAE) is a CD4(+) Th1-mediated demyelinating disease of the CNS that serves as a model for multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific and Ag-nonspecific T lymphocytes into the CNS. In the present report, we investigated the role of the CXC chemokine CXCL10 (IFN-gamma-inducible protein-10) in the pathogenesis of EAE. Production of CXCL10 in the CNS correlated with the development of clinical disease. Administration of anti-CXCL10 decreased clinical and histological disease incidence, severity, as well as infiltration of mononuclear cells into the CNS. Anti-CXCL10 specifically decreased the accumulation of encephalitogenic PLP(139-151) Ag-specific CD4+ T cells in the CNS compared with control-treated animals. Anti-CXCL10 administration did not affect the activation of encephalitogenic T cells as measured by Ag-specific proliferation and the ability to adoptively transfer EAE. These results demonstrate an important role for the CXC chemokine CXCL10 in the recruitment and accumulation of inflammatory mononuclear cells during the pathogenesis of EAE.
实验性自身免疫性脑脊髓炎（EAE）是一种由CD4(+) Th1介导的中枢神经系统脱髓鞘疾病，可作为多发性硬化症的模型。EAE发病机制中的一个关键事件是抗原特异性和非特异性T淋巴细胞进入中枢神经系统。在本报告中，我们研究了CXC趋化因子CXCL10（干扰素-γ诱导蛋白-10）在EAE发病机制中的作用。中枢神经系统中CXCL10的产生与临床疾病的发展相关。给予抗CXCL10可降低临床和组织学疾病的发病率、严重程度，以及单核细胞向中枢神经系统的浸润。与对照处理的动物相比，抗CXCL10特异性降低了致脑炎性髓鞘少突胶质细胞糖蛋白（PLP）(139-151)抗原特异性CD4+ T细胞在中枢神经系统中的积累。通过抗原特异性增殖和过继转移EAE的能力来衡量，给予抗CXCL10并不影响致脑炎性T细胞的活化。这些结果表明CXC趋化因子CXCL10在EAE发病机制中炎症单核细胞的募集和积累方面发挥重要作用。
