ABSENCE OF MHC CLASS-II MOLECULES REDUCES CNS DEMYELINATION, MICROGLIAL/MACROPHAGE INFILTRATION, AND TWITCHING IN MURINE GLOBOID-CELL LEUKODYSTROPHY

Globoid cell leukodystrophy (GLD) is a severe genetic demyelinating disorder with an increased number of la (immune response antigen) positive brain microglial 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 eels 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.