In vivo expression of major histocompatibility complex molecules on oligodendrocytes and neurons during viral infection.
Demyelination in multiple sclerosis and in animal models is associated with infiltrating CD8+ and CD4+ T cells. Although oligodendrocytes and axons are damaged in these diseases, the roles T cells play in the demyelination process are not completely understood. Antigen-specific CD8+ T cell lysis of target cells is dependent on interactions between the T cell receptor and major histocompatibility complex (MHC) class I-peptide complexes on the target cell. In the normal central nervous system, expression of MHC molecules is very low but often increases during inflammation. We set out to precisely define which central nervous system cells express MHC molecules in vivo during infection with a strain of murine hepatitis virus that causes a chronic, inflammatory demyelinating disease. Using double immunofluorescence labeling, we show that during acute infection with murine hepatitis virus, MHC class I is expressed in vivo by oligodendrocytes, neurons, microglia, and endothelia, and MHC class II is expressed only by microglia. These data indicate that oligodendrocytes and neurons have the potential to present antigen to T cells and thus be damaged by direct antigen-specific interactions with CD8+ T lymphocytes.
Redwine
J M
JM
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California, USA.
Buchmeier
M J
MJ
Evans
C F
CF
D000818:Animals; D018352:Coronavirus Infections / Q000378:metabolism* / Q000473:pathology; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D014644:Genetic Variation; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000378:metabolism; D006517:Murine hepatitis virus / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D013118:Spinal Cord Diseases / Q000378:metabolism* / Q000473:pathology
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II