Susceptibility to Theiler's virus-induced demyelinating disease correlates with astrocyte class II induction and antigen presentation.
Theiler's murine encephalomyelitis virus (TMEV) is a picornavirus which induces a chronic demyelinating disease of the central nervous system (CNS) in certain susceptible mouse strains. Demyelination has been shown to result from immunopathological responses mediated by CD4+, major histocompatibility complex (MHC) class II-restricted T cells. As little or no class II is expressed in the normal mouse CNS, the ability of astrocytes to express these proteins and present antigen to T cells from TMEV-infected mice was investigated here. It is shown that astrocytes are capable of presenting TMEV to virus-specific T cells in vitro, and that this ability is dependent on prior induction of MHC class II by interferon-gamma (IFN-gamma) treatment. Unlike other viruses such as murine hepatitis virus-JHM (a coronavirus) and measles, TMEV is not capable of inducing class II on astrocytes directly. There is a correlation between the ease of class II induction on astrocytes from different mouse strains by IFN-gamma and mouse strain susceptibility to TMEV-induced demyelinating disease. These results suggest that following viral infection and initial T-cell infiltration into the CNS, class II induction on astrocytes is a key step allowing local antigen presentation and amplification of immunopathological responses within the CNS and hence the development of demyelinating disease.
Borrow
P
P
Department of Pathology, University of Cambridge, U.K.
Nash
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AA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D001253:Astrocytes / Q000276:immunology*; D002478:Cells, Cultured; D004198:Disease Susceptibility; D004769:Enterovirus Infections / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007371:Interferon-gamma / Q000276:immunology; D004680:Maus Elberfeld virus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology
D000956:Antigens, Viral; D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D007371:Interferon-gamma