title: Enhancement of disease by neutralizing antiviral antibodies in the absence of primed antiviral cytotoxic T cells.
abstract: The effects of neutralizing antibodies on the disease course in mice infected with the noncytopathic lymphocytic choriomeningitis virus (LCMV) were evaluated. Whereas non-neutralizing antisera exhibiting high enzyme-linked immunosorbent assay titers had no effect on T cell responses and their consequences, neutralizing antisera modulated them variably. Neutralizing antibodies were able to prevent lethal choriomeningitis after intracerebral infection with a neurotropic LCMV-isolate (ARMSTRONG) although they could not control local virus replication. The same antibodies exhibited little or no protective effect on choriomeningitis induced by LCMV-WE, a viscerotrope isolate. Surprisingly, these antibodies rendered mice much more susceptible to choriomeningitis after intracerebral infection with LCMV DOCILE, a very rapidly spreading lymphocyto-viscerotrope virus; in this situation antibodies prevented overwhelming infection which causes deletion of immunopathogenic cytotoxic T cell responses. Thus preexisting neutralizing antiviral antibodies had little influence on local virus spread in peripheral tissues but they reduced hematogenic spread and infection of antigen-presenting cells; thereby they influenced the primary cytotoxic T cell (CTL) response and indirectly modulated the extent of T cell-mediated immunopathology in peripheral organs. These results may explain why vaccines inducing neutralizing antibodies but no CTL may enhance an immunopathological disease caused by challenge infection with a noncytopathic virus.
authors.affiliation: Department of Pathology, University of Zürich, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Battegay
authors.forename: D
authors.initials: D
authors.lastname: Kyburz
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000502:physiology*; D007106:Immune Sera / Q000276:immunology; D007116:Immunization, Passive; D008216:Lymphocytic Choriomeningitis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007106:Immune Sera; D014765:Viral Vaccines