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  • Title: Absence of MHC class II molecules reduces CNS demyelination, microglial/macrophage infiltration, and twitching in murine globoid cell leukodystrophy.
    Author: Matsushima GK, Taniike M, Glimcher LH, Grusby MJ, Frelinger JA, Suzuki K, Ting JP.
    Journal: Cell; 1994 Aug 26; 78(4):645-56. PubMed ID: 8069913.
    Abstract:
    Globoid cell leukodystrophy (GLD) is a severe genetic demyelinating disorder with an increased number of Ia (immune response antigen) positive brain microglia/macrophages. To assess the role of aberrant Ia expression in the central nervous system (CNS), twitcher mice, which represent the murine model for GLD, were mated with Ia- transgenic mice. Compared with the Ia+ controls, Ia- twitcher mice showed a profound reduction in the severity of demyelinating lesions correlated with significantly fewer microglia/macrophages. Most importantly, Ia- twitcher mice showed significantly reduced twitching compared with ia+ twitcher mice. In contrast with experimental allergic encephalomyelitis (EAE), there was no significant amount of inflammatory T cell infiltrates, implying that T cells may not play a predominant role in this disease. These findings may have broad therapeutic implications for Alzheimer's disease, Parkinson's disease, and Huntington's disease, which display enhanced Ia expression in the CNS without obvious T cell infiltrates.
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