title: CD8+ T cells complement antibodies in protecting against yellow fever virus.
abstract: The attenuated yellow fever (YF) vaccine (YF-17D) was developed in the 1930s, yet little is known about the protective mechanisms underlying its efficiency. In this study, we analyzed the relative contribution of cell-mediated and humoral immunity to the vaccine-induced protection in a murine model of YF-17D infection. Using different strains of knockout mice, we found that CD4(+) T cells, B cells, and Abs are required for full clinical protection of vaccinated mice, whereas CD8(+) T cells are dispensable for long-term survival after intracerebral challenge. However, by analyzing the immune response inside the infected CNS, we observed an accelerated T cell influx into the brain after intracerebral challenge of vaccinated mice, and this T cell recruitment correlated with improved virus control in the brain. Using mice deficient in B cells we found that, in the absence of Abs, YF vaccination can still induce some antiviral protection, and in vivo depletion of CD8(+) T cells from these animals revealed a pivotal role for CD8(+) T cells in controlling virus replication in the absence of a humoral response. Finally, we demonstrated that effector CD8(+) T cells also contribute to viral control in the presence of circulating YF-specific Abs. To our knowledge, this is the first time that YF-specific CD8(+) T cells have been demonstrated to possess antiviral activity in vivo.
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Maria R
authors.initials: MR
authors.lastname: Bassi
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Michael
authors.initials: M
authors.lastname: Kongsgaard
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Maria A
authors.initials: MA
authors.lastname: Steffensen
authors.affiliation: Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, DK-5000 Odense, Denmark; and.
authors.forename: Christina
authors.initials: C
authors.lastname: Fenger
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Michael
authors.initials: M
authors.lastname: Rasmussen
authors.affiliation: Department of Cancer and Inflammation, Institute for Molecular Medicine, University of Southern Denmark, DK-5000 Odense, Denmark.
authors.forename: Karsten
authors.initials: K
authors.lastname: Skjødt
authors.affiliation: Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, DK-5000 Odense, Denmark; and.
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Anette
authors.initials: A
authors.lastname: Stryhn
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Søren
authors.identifier: http://orcid.org/0000-0001-8363-1999
authors.initials: S
authors.lastname: Buus
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark;
authors.forename: Jan P
authors.initials: JP
authors.lastname: Christensen
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, DK-2200 Copenhagen N, Denmark; athomsen@sund.ku.dk.
authors.forename: Allan R
authors.initials: AR
authors.lastname: Thomsen
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007116:Immunization, Passive; D008212:Lymphocyte Depletion; D051379:Mice; D018345:Mice, Knockout; D014611:Vaccination; D014779:Virus Replication; D015004:Yellow Fever / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D022341:Yellow Fever Vaccine / Q000276:immunology; D015005:Yellow fever virus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022341:Yellow Fever Vaccine; D023201:CD40 Ligand