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 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.
Matsushima
G K
GK
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599.
Taniike
M
M
Glimcher
L H
LH
Grusby
M J
MJ
Frelinger
J A
JA
Suzuki
K
K
Ting
J P
JP
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001854:Bone Marrow Cells; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005260:Female; D005698:Galactosylceramidase; D005802:Genes, MHC Class II / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007965:Leukodystrophy, Globoid Cell / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology*; D009154:Mutation / Q000502:physiology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D005698:Galactosylceramidase