Cutting edge: CD8 T cell-mediated demyelination is IFN-gamma dependent in mice infected with a neurotropic coronavirus.
Mice infected with the murine coronavirus, mouse hepatitis virus, strain JHM (MHV) develop an immune-mediated demyelinating encephalomyelitis. We showed previously that adoptive transfer of MHV-immune splenocytes depleted of either CD4 or CD8 T cells to infected RAG1(-/-) recipients (mice deficient in recombination activation gene 1) resulted in demyelination. Herein we show that transfer of CD8 T cell-enriched splenocytes from MHV-immune IFN-gamma(-/-) donors resulted in a substantial decrease in demyelination (4.8% of the white matter of the spinal cord compared with 26.3% in those receiving cells from C57BL/6 donors). Similar numbers of lymphocytes were present in the CNS of recipients of either C57BL/6 or IFN-gamma(-/-) CD8 T cells, suggesting that IFN-gamma was not crucial for lymphocyte entry into the CNS. Rather, IFN-gamma was critical for optimal activation or migration of macrophages or microglia into the white matter in the context of CD8 T cell-mediated demyelination.
Pewe
Lecia
L
Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA.
Perlman
Stanley
S
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002465:Cell Movement; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007371:Interferon-gamma / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000276:immunology; D006517:Murine hepatitis virus / Q000302:isolation & purification; D009186:Myelin Sheath / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D013154:Spleen / Q000276:immunology
D007371:Interferon-gamma