title: The early activation of CD8+ T cells is dependent on type I IFN signaling following intramuscular vaccination of adenovirus vector.
abstract: Few of the vaccines in current use can induce antigen- (Ag-) specific immunity in both mucosal and systemic compartments. Hence, the development of vaccines that realize both mucosal and systemic protection against various pathogens is a high priority in global health. Recently, it has been reported that intramuscular (i.m.) vaccination of an adenovirus vector (Adv) can induce Ag-specific cytotoxic T lymphocytes (CTLs) in both systemic and gut mucosal compartments. We previously revealed that type I IFN signaling is required for the induction of gut mucosal CTLs, not systemic CTLs. However, the molecular mechanism via type I IFN signaling is largely unknown. Here, we report that type I IFN signaling following i.m. Adv vaccination is required for the expression of type I IFN in the inguinal lymph nodes (iLNs), which are the draining lymph nodes of the administration site. We also showed that the type I IFN signaling is indispensable for the early activation of CTLs in iLNs. These data suggested that type I IFN signaling has an important role in the translation of systemic innate immune response into mucosal adaptive immunity by amplifying the innate immune signaling and activating CTLs in the iLN.
authors: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Masahisa
authors: M
authors: Hemmi
authors: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Masashi
authors: 0000-0002-0376-508X
authors: M
authors: Tachibana
authors: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Sayaka
authors: S
authors: Tsuzuki
authors: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Masaki
authors: M
authors: Shoji
authors: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan ; Laboratory of Regulatory Sciences for Oligonucleotide Therapeutics, Clinical Drug Development Unit, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Fuminori
authors: F
authors: Sakurai
authors: Laboratory of Stem Cell Regulation, National Institute of Biomedical Innovation, 7-6-8 Asagi, Saito, Ibaraki, Osaka 567-0085, Japan.
authors: Kenji
authors: K
authors: Kawabata
authors: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, 7-6-8 Asagi, Saito, Ibaraki, Osaka 567-0085, Japan ; Laboratory of Vaccine Science, World Premier International Research Center Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Kouji
authors: K
authors: Kobiyama
authors: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, 7-6-8 Asagi, Saito, Ibaraki, Osaka 567-0085, Japan ; Laboratory of Vaccine Science, World Premier International Research Center Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Ken J
authors: KJ
authors: Ishii
authors: Laboratory of Host Defense, World Premier International Research Center Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan ; Department of Host Defense, The Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Shizuo
authors: S
authors: Akira
authors: Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan ; iPS Cell-Based Research Project on Hepatic Toxicity and Metabolism, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan ; Laboratory of Hepatocyte Differentiation, National Institute of Biomedical Innovation, 7-6-8 Asagi, Saito, Ibaraki, Osaka 567-0085, Japan ; The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Hiroyuki
authors: H
authors: Mizuguchi
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005822:Genetic Vectors; D007113:Immunity, Innate; D018928:Immunity, Mucosal / Q000276:immunology*; D007273:Injections, Intramuscular; D007370:Interferon Type I / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009092:Mucous Membrane / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination
chemical_list: D007370:Interferon Type I