title: T cell-dependent IFN-gamma exerts an antiviral effect in the central nervous system but not in peripheral solid organs.
abstract: The antiviral relevance of soluble mediators that may operate in the vicinity of virus specific effector T cells was investigated. Mice were immunized with vesicular stomatitis virus (VSV) wild type (wt) and subsequently challenged with a mixture of two vaccinia recombinant viruses, one expressing the nucleoprotein of VSV (vacc-VSV-NP) the other expressing the glycoprotein of lymphocytic choriomeningitis virus (vacc-LCMV-GP). It was determined whether or not the VSV wt-induced memory T cell response that is protective against vacc-VSV-NP would inhibit growth of the nonrecognized vacc-LCMV-GP. In ovaries and testes replication of vacc-LCMV-GP was not inhibited. In contrast, the T cell response against vacc-VSV-NP nonspecifically inhibited growth of the non-recognized vacc-LCMV-GP in the central nervous system. This inhibiting effect was partly abrogated by treatment with anti-IFN-gamma antiserum but not by an anti-TNF-alpha antiserum. Similar results were obtained in VSV wt-immune H-2b mice, which eliminate vacc-VSV-NP by CD8+ T cells and in H-2k mice, which eliminate vacc-VSV-NP by a CD4+ T cell-dependent mechanism. These data suggest that a protective bystander effect mediated by soluble CD8+ and CD4+ T cell-dependent factors may be demonstrated against vaccinia virus only in an organ such as the central nervous system in which the blood-brain barrier inhibits diffusion and draining of the soluble antiviral factors released by specific effector T cells.
authors.affiliation: Institute of Experimental Immunology, University of Zürich, Switzerland.
authors.forename: T M
authors.initials: TM
authors.lastname: Kündig
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D005260:Female; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010053:Ovary / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D013601:T-Lymphocytes / Q000276:immunology*; D013737:Testis / Q000187:drug effects / Q000276:immunology / Q000382:microbiology*; D014616:Vaccinia virus / Q000187:drug effects / Q000254:growth & development*
chemical_list: D007371:Interferon-gamma