title: Preferential induction of protective T cell responses to Theiler's virus in resistant (C57BL/6 x SJL)F1 mice.
abstract: Infection of the central nervous system (CNS) with Theiler's murine encephalomyelitis virus (TMEV) induces an immune-mediated demyelinating disease in susceptible mouse strains such as SJL/J (H-2(s)) but not in strains such as C57BL/6 (H-2(b)). In addition, it has been shown that (C57BL/6 × SJL/J)F1 mice (F1 mice), which carry both resistant and susceptible MHC haplotypes (H-2(b/s)), are resistant to both viral persistence and TMEV-induced demyelinating disease. In this study, we further analyzed the immune responses underlying the resistance of F1 mice. Our study shows that the resistance of F1 mice is associated with a higher level of the initial virus-specific H-2(b)-restricted CD8(+) T cell responses than of the H-2(s)-restricted CD8(+) T cell responses. In contrast, pathogenic Th17 responses to viral epitopes are lower in F1 mice than in susceptible SJL/J mice. Dominant effects of resistant genes expressed in antigen-presenting cells of F1 mice on regulation of viral replication and induction of protective T cell responses appear to play a crucial role in disease resistance. Although the F1 mice are resistant to disease, the level of viral RNA in the CNS was intermediate between those of SJL/J and C57BL/6 mice, indicating the presence of a threshold of viral expression for pathogenesis.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611, USA.
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Jin
authors.forename: Hyun Seok
authors.initials: HS
authors.lastname: Kang
authors.forename: Mani
authors.initials: M
authors.lastname: Mohindru
authors.forename: Byung S
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000818:Animals; D018188:Cardiovirus Infections / Q000235:genetics / Q000276:immunology*; D003433:Crosses, Genetic; D007113:Immunity, Innate / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D017945:Theilovirus / Q000276:immunology*