Vaccination protects beta 2 microglobulin deficient mice from immune mediated mortality but not from persisting viral infection.
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.
Hildeman
D
D
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison 53706, USA.
Salvato
M
M
Whitton
J L
JL
Muller
D
D
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*
D014765:Viral Vaccines; D001613:beta 2-Microglobulin