Role of IFN-gamma responsiveness in CD8 T-cell-mediated viral clearance and demyelination in coronavirus-infected mice.
Immunocompetent, but not RAG1(-/-) mice infected with MHV-JHM develop demyelination. Transferred CD8 T cell-enriched splenocytes reconstitute demyelination, and this ability is dependent on donor IFN-gamma. We used IFN-gammaR1(-/-) mice to examine the target of IFN-gamma in CD8 T cell-mediated demyelination. In IFN-gammaR1(-/-)RAG1(-/-) recipients, demyelination is decreased, but not eliminated, while viral titers are significantly increased when compared to IFN-gammaR1(+/+)RAG1(-/-) recipients. IFN-gammaR1(-/-) CD8 T cells retain virus-specific effector function regardless of IFN-gammaR1 expression. Although IFN-gammaR1 responsiveness is critical for maximal demyelination, increased levels of infectious virus coupled with adoptive transfer of CD8 T cells may result in myelin destruction independent of IFN-gammaR1 expression.
Templeton
Steven P
SP
Interdisciplinary Program in Immunology, University of Iowa, Iowa City, IA 52242, United States. steven-templeton@uiowa.edu
Perlman
Stanley
S
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D020805:Central Nervous System Viral Diseases / Q000276:immunology* / Q000473:pathology / Q000821:virology; D002633:Chemotaxis; D018352:Coronavirus Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003433:Crosses, Genetic; D020278:Demyelinating Autoimmune Diseases, CNS / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D007371:Interferon-gamma / Q000032:analysis / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006517:Murine hepatitis virus / Q000302:isolation & purification / Q000502:physiology*; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000637:transplantation; D000096743:Interferon gamma Receptor
D018398:Homeodomain Proteins; D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor; C064658:RAG-1 protein