title: Characterization of an immediate splenic precursor of CD8+ dendritic cells capable of inducing antiviral T cell responses.
abstract: Mouse spleens contain three major dendritic cell (DC) populations: plasmacytoid DC, conventional CD8(+)CD24(+) DC (CD8(+) DC), and conventional CD8(-)CD24(-) DC (CD8(-) DC). We have previously shown that CD8(+) DC are the major cross-presenting subtype in vivo and are the main inducers of antiviral cytotoxic T lymphocyte responses. Here we show that after depletion of CD8(+) DC, the only DC capable of viral Ag presentation was a small subset that expresses CD24 but not CD8. This CD8(-)CD24(+) DC population is greatly expanded in mice treated with the DC growth factor FMS-like tyrosine kinase 3 ligand. The CD8(-)CD24(+) DC represent an immediate precursor of CD8(+) DC, as demonstrated by their expression pattern of characteristic markers of CD8(+) DC, their capacity to cross-present in vitro, and their conversion into CD8(+) DC upon adoptive transfer into recipient mice. Accordingly, the lifespan of transferred CD8(-)CD24(+) DC in vivo was greatly enhanced as compared with terminally differentiated CD8(+) DC. Moreover, in a vaccination protocol, CD8(-)CD24(+) DC induced stronger T cell responses and accelerated viral clearance of HSV-1 compared with CD8(+) DC. Our results demonstrate that the ability to cross-present first appears in an immediate precursor population of CD8(+) DC that does not yet express CD8. The enhanced capacity of CD8(-)CD24(+) DC to induce immune responses upon adoptive transfer makes them an attractive novel tool for DC-based immunotherapies.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
authors.forename: Sammy
authors.initials: S
authors.lastname: Bedoui
authors.forename: Sandro
authors.initials: S
authors.lastname: Prato
authors.forename: Justine
authors.initials: J
authors.lastname: Mintern
authors.forename: Thomas
authors.initials: T
authors.lastname: Gebhardt
authors.forename: Yifan
authors.initials: Y
authors.lastname: Zhan
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lew
authors.forename: William R
authors.initials: WR
authors.lastname: Heath
authors.forename: José A
authors.initials: JA
authors.lastname: Villadangos
authors.forename: Elodie
authors.initials: E
authors.lastname: Segura
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015153:Blotting, Western; D051927:CD24 Antigen / Q000276:immunology / Q000378:metabolism; D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D018259:Herpesvirus 1, Human / Q000276:immunology*; D015395:Histocompatibility Antigens Class I; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013234:Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology
chemical_list: D051927:CD24 Antigen; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I