Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE).
Mice with a disrupted IFN-gamma gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE).
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DOI：
10.4049/jimmunol.156.1.5
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发表时间：
1996-01
影响因子：
4.4
通讯作者：
I. Ferber;S. Brocke;C. Taylor-Edwards;W. Ridgway;C. Dinisco;L. Steinman;D. Dalton;C. Fathman
中科院分区：
文献类型：
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作者：
I. Ferber;S. Brocke;C. Taylor-Edwards;W. Ridgway;C. Dinisco;L. Steinman;D. Dalton;C. Fathman
实验性自身免疫性脑脊髓炎（EAE）是多发性硬化症的动物模型，是在用髓鞘碱性蛋白（MBP）或MBP衍生肽免疫后在小鼠和大鼠中观察到的自身免疫性疾病。IFN-γ是一种由多种细胞产生的细胞因子，参与许多炎症和免疫调节事件。在患有多发性硬化症的人中注射IFN-γ与在患有EAE的小鼠中使用抗IFN-γ Ab的研究相比，观察到关于恶化和病程的矛盾结果。为了研究IFN-γ和产生IFN-γ的细胞在EAE中的作用，我们将IFN-γ敲除小鼠（H-2b）（由于IFN-γ基因的破坏而不能产生IFN-γ）与EAE易感小鼠品系B10.PL（H-2u）杂交。在用MBP免疫后，在IFN-γ敲除小鼠、杂合子（IFN-γ +/-）小鼠以及野生型同窝小鼠中观察到EAE。IFN-γ基因敲除EAE小鼠中枢神经系统的组织学分析显示大量的淋巴细胞、巨噬细胞和粒细胞浸润。我们的结论是，IFN-γ的存在是不重要的诱导或EAE的临床过程。
Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is an autoimmune disorder seen in mice and rats following immunization with myelin basic protein (MBP) or MBP-derived peptides. IFN-gamma, a cytokine produced by a variety of cells, is involved in many inflammatory and immune regulatory events. Contradictory results concerning exacerbations and the disease course were seen comparing injections of IFN-gamma in humans suffering from multiple sclerosis to studies using anti-IFN-gamma Abs in mice with EAE. To study the role of IFN-gamma and IFN-gamma-producing cells in EAE, we crossed IFN-gamma knockout mice (H-2b) (unable to produce IFN-gamma due to the disruption of the IFN-gamma gene) with an EAE-susceptible mouse strain, B10.PL (H-2u). EAE was seen in IFN-gamma knockout mice, heterozygotic (IFN-gamma +/-) mice, as well as wild-type littermates following immunization with MBP. Histologic analyses of the central nervous system of IFN-gamma knockout mice with EAE revealed massive infiltrates composed of lymphocytes, macrophages, and granulocytes. We conclude that the presence of IFN-gamma is not crucial to the induction or the clinical course of EAE.