Bystander CD8 T-cell-mediated demyelination is interferon-gamma-dependent in a coronavirus model of multiple sclerosis.
Mice infected with the coronavirus mouse hepatitis virus, strain JHM (JHM) develop a disease that shares many histological characteristics with multiple sclerosis. We previously demonstrated that JHM-infected mice that only have CD8 T cells specific for an epitope not in the virus develop demyelination on specific activation of these cells. Herein we show that this process of bystander T-cell-mediated demyelination is interferon-gamma (IFN-gamma)-dependent. The absence of IFN-gamma abrogated demyelination but did not change T-cell infiltration or expression levels of inflammatory cytokines or chemokines in the spinal cord. These results are consistent with models in which IFN-gamma contributes to CD8 T-cell-mediated demyelination by activation of macrophages/microglia, the final effector cells in the disease process.
Dandekar
Ajai A
AA
Interdisciplinary Program in Immunology, University of Iowa, Iowa City, Iowa 52242, USA.
Anghelina
Daniela
D
Perlman
Stanley
S
D000818:Animals; D024201:Bystander Effect / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D017934:Coronavirus / Q000276:immunology; D018352:Coronavirus Infections / Q000276:immunology; D003711:Demyelinating Diseases / Q000276:immunology* / Q000821:virology; D004681:Encephalomyelitis, Autoimmune, Experimental; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology* / Q000821:virology; D018183:Transplantation Chimera
D007371:Interferon-gamma