Absence of MHC class ii molecules reduces CNS demyelination, microglial/macrophage infiltration, and twitching in murine globoid cell leukodystrophy

Globoid cell leukodystrophy (GILD) is a severe genetic demyelinating disorder with an increased number of la (immune response antigen) positive brain microglia/ macrophages. To assess the role of aberrant la expression in the central nervous system (CNS), twitcher mice, which represent the murine model for GLD, were mated with la^-- transgenic mice. Compared with the la⁺ controls, la^- twitcher mice showed a profound reduction in the severity of demyelinating lesions correlated with significantly fewer microglia/macrophages. Most importantly, la^- twitcher mice showed significantly reduced twitching compared with la⁺ 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 la expression in the CNS without obvious T cell Infiltrates.