Myelin oligodendrocyte glycoprotein-induced autoimmune encephalomyelitis is chronic/relapsing in perforin knockout mice, but monophasic in Fas- and Fas ligand-deficient lpr and gld mice

被引:96
作者
Malipiero, U
Frei, K
Spanaus, KS
Agresti, C
Lassmann, H
Hahne, M
Tschopp, J
Eugster, HP
Fontana, A
机构
[1] Univ Zurich Hosp, Dept Internal Med, Clin Immunol Sect, CH-8044 Zurich, Switzerland
[2] Univ Zurich Hosp, Dept Neurosurg, CH-8044 Zurich, Switzerland
[3] Ist Super Sanita, Lab Organ & Syst Pathophysiol, Neurobiol Sect, I-00161 Rome, Italy
[4] Univ Vienna, Inst Neurol Expt Neuropathol Neuroimmunol, Vienna, Austria
[5] Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland
关键词
experimental autoimmune encephalomyelitis; Fas; Fas ligand; perforin; myelin oligodendrocyte glycoprotein;
D O I
10.1002/eji.1830271211
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The expression and action of Fas/Fas ligand (FasL) in multiple sclerosis has been postulated as a major pathway leading to inflammatory demyelination. To formally test this hypothesis, C57BL/6-lpr and -gld mice, which due to gene mutation express Fas and Fast in an inactive form, were immunized with myelin oligodendrocyte glycoprotein peptide(35-55). Whereas in wild-type C57BL/6 mice, experimental autoimmune encephalomyelitis (EAE), was chronic/relapsing, EAE in lpr and gld mice was characterized by a lower incidence of disease and a monophasic course. This contrasts with C57BL/6 perforin knockout mice, which showed the most severe form of EAE of all mouse strains tested, the course being chronic relapsing. The difference noted cannot be attributed to an involvement of Fast in oligodendrocyte damage since oligodendrocytes are insensitive to Fast-mediated cytotoxicity in vitro, and since in the acute phase of EAE gld mice also show CD4(+) T cell infiltrates with associated demyelination in brain and spinal cord. Unlike oligodendrocytes, astrocytes were killed by Fast in vitro. It remains to be established whether this latter finding explains the different disease course of lpr and gld mice compared to wild-type and perforin knockout mice.
引用
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页码:3151 / 3160
页数:10
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