title: Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells.
abstract: In recent years, human dendritic cells (DCs) could be subdivided into CD304+ plasmacytoid DCs (pDCs) and conventional DCs (cDCs), the latter encompassing the CD1c+, CD16+, and CD141+ DC subsets. To date, the low frequency of these DCs in human blood has essentially prevented functional studies defining their specific contribution to antigen presentation. We have established a protocol for an effective isolation of pDC and cDC subsets to high purity. Using this approach, we show that CD141+ DCs are the only cells in human blood that express the chemokine receptor XCR1 and respond to the specific ligand XCL1 by Ca2+ mobilization and potent chemotaxis. More importantly, we demonstrate that CD141+ DCs excel in cross-presentation of soluble or cell-associated antigen to CD8+ T cells when directly compared with CD1c+ DCs, CD16+ DCs, and pDCs from the same donors. Both in their functional XCR1 expression and their effective processing and presentation of exogenous antigen in the context of major histocompatibility complex class I, human CD141+ DCs correspond to mouse CD8+ DCs, a subset known for superior antigen cross-presentation in vivo. These data define CD141+ DCs as professional antigen cross-presenting DCs in the human.
authors.affiliation: Molecular Immunology, Robert Koch-Institute, 13353 Berlin, Germany.
authors.forename: Annabell
authors.initials: A
authors.lastname: Bachem
authors.forename: Steffen
authors.initials: S
authors.lastname: Güttler
authors.forename: Evelyn
authors.initials: E
authors.lastname: Hartung
authors.forename: Frédéric
authors.initials: F
authors.lastname: Ebstein
authors.forename: Michael
authors.initials: M
authors.lastname: Schaefer
authors.forename: Astrid
authors.initials: A
authors.lastname: Tannert
authors.forename: Abdulgabar
authors.initials: A
authors.lastname: Salama
authors.forename: Kamran
authors.initials: K
authors.lastname: Movassaghi
authors.forename: Corinna
authors.initials: C
authors.lastname: Opitz
authors.forename: Hans W
authors.initials: HW
authors.lastname: Mages
authors.forename: Volker
authors.initials: V
authors.lastname: Henn
authors.forename: Peter-Michael
authors.initials: PM
authors.lastname: Kloetzel
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gurka
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kroczek
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D039521:CD11c Antigen / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D020013:Calcium Signaling / Q000276:immunology; D002633:Chemotaxis / Q000276:immunology; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D010750:Phosphoproteins / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D012995:Solubility; D018180:Thrombomodulin / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000276:immunology
chemical_list: D039521:CD11c Antigen; D010750:Phosphoproteins; D043562:Receptors, G-Protein-Coupled; D017452:Receptors, IgG; C546931:THBD protein, human; D018180:Thrombomodulin; D014763:Viral Matrix Proteins; C091671:XCR1 protein, human; C065418:cytomegalovirus matrix protein 65kDa