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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.

Type

Journal article

Journal

Immunology

Publication Date

05/1992

Volume

76

Pages

133 - 139

Keywords

Animals, Antigen-Presenting Cells, Antigens, Viral, Astrocytes, Cells, Cultured, Disease Susceptibility, Enterovirus Infections, Histocompatibility Antigens Class II, Interferon-gamma, Maus Elberfeld virus, Mice, Mice, Inbred BALB C, Mice, Inbred CBA, Mice, Inbred Strains, Recombinant Proteins, T-Lymphocytes