title: CD8α(-) Dendritic Cells Induce Antigen-Specific T Follicular Helper Cells Generating Efficient Humoral Immune Responses.
abstract: Recent studies on T follicular helper (Tfh) cells have significantly advanced our understanding of T cell-dependent B cell responses. However, little is known about the early stage of Tfh cell commitment by dendritic cells (DCs), particularly by the conventional CD8α(+) and CD8α(-) DC subsets. We show that CD8α(-) DCs localized at the interfollicular zone play a pivotal role in the induction of antigen-specific Tfh cells by upregulating the expression of Icosl and Ox40l through the non-canonical NF-κB signaling pathway. Tfh cells induced by CD8α(-) DCs function as true B cell helpers, resulting in significantly increased humoral immune responses against various human pathogenic antigens, including Yersinia pestis LcrV, HIV Gag, and hepatitis B surface antigen. Our findings uncover a mechanistic role of CD8α(-) DCs in the initiation of Tfh cell differentiation and thereby provide a rationale for investigating CD8α(-) DCs in enhancing antigen-specific humoral immune responses for improving vaccines and therapeutics.
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors.forename: Changsik
authors.initials: C
authors.lastname: Shin
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors.forename: Jae-A
authors.initials: JA
authors.lastname: Han
authors.affiliation: Laboratory of Cellular Physiology and Immunology and Chris Browne Center, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Hyein
authors.initials: H
authors.lastname: Koh
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors.forename: Bongseo
authors.initials: B
authors.lastname: Choi
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors.forename: Yongbin
authors.initials: Y
authors.lastname: Cho
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors.forename: Hyeongmin
authors.initials: H
authors.lastname: Jeong
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors.forename: Jea-Sun
authors.initials: JS
authors.lastname: Ra
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-338, Republic of Korea.
authors.forename: Pil Soo
authors.initials: PS
authors.lastname: Sung
authors.affiliation: Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-338, Republic of Korea.
authors.forename: Eui-Cheol
authors.initials: EC
authors.lastname: Shin
authors.affiliation: Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Chonan-Si, Chungcheongnam-do 336-745, Republic of Korea. Electronic address: ryu@sch.ac.kr.
authors.forename: Seongho
authors.initials: S
authors.lastname: Ryu
authors.affiliation: School of Life Sciences, Ulsan National Institute of Science and Technology, UNIST-gil 50, Ulsan 689-798, Republic of Korea.
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Do
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D056724:Immunity, Humoral / Q000235:genetics*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D015010:Yersinia pestis / Q000276:immunology / Q000472:pathogenicity
chemical_list: D006514:Hepatitis B Surface Antigens; D016328:NF-kappa B