title: Vaccination protects beta 2 microglobulin deficient mice from immune mediated mortality but not from persisting viral infection.
abstract: Intracranial (i.c.) infection of immunocompetent mice with lymphocytic choriomeningitis virus (LCMV) results in immunopathological lethal meningitis mediated by CD8+ cytotoxic T lymphocytes (CTL). Vaccination of immunocompetent mice elicits a CD8+ CTL response that can protect the mice from lethal meningitis. beta 2 microglobulin-deficient (beta 2m-/-) mice are deficient in CD8+ CTL, exhibit CD4+ CTL, and, after i.c. LCMV infection, undergo a less severe meningitis with decreased mortality and additionally develop a wasting disease. Both wasting disease and mortality in beta 2m-/- mice are mediated by CD4+ T cells. We studied the effects of vaccination and challenge dose on weight loss, mortality and viral clearance after i.c. LCMV infection in beta 2m-/- mice. Unvaccinated beta 2m-/- mice had significant weight loss and mortality at doses of 200 and 10(3) p.f.u. LCMV, while a dose of 10(6) p.f.u. LCMV elicited significant mortality but less weight loss. Vaccination with u.v.-inactivated LCMV in complete Freund's adjuvant or with vaccinia virus expressing the LCMV glycoprotein or nucleoprotein genes protected beta 2m-/- mice from mortality but not weight loss after 200 p.f.u. LCMV challenge. Although protected from mortality, beta 2m-/- mice were unable to clear LCMV from their brains or spleens. Therefore, we show that vaccination can protect against lethal immune-meningitis in the face of persistent infection.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison 53706, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hildeman
authors.forename: M
authors.initials: M
authors.lastname: Salvato
authors.forename: J L
authors.initials: JL
authors.lastname: Whitton
authors.forename: D
authors.initials: D
authors.lastname: Muller
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D008216:Lymphocytic Choriomeningitis / Q000401:mortality / Q000517:prevention & control*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination; D014765:Viral Vaccines / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000172:deficiency*
chemical_list: D014765:Viral Vaccines; D001613:beta 2-Microglobulin