Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells.
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.
Bachem
Annabell
A
Molecular Immunology, Robert Koch-Institute, 13353 Berlin, Germany.
Güttler
Steffen
S
Hartung
Evelyn
E
Ebstein
Frédéric
F
Schaefer
Michael
M
Tannert
Astrid
A
Salama
Abdulgabar
A
Movassaghi
Kamran
K
Opitz
Corinna
C
Mages
Hans W
HW
Henn
Volker
V
Kloetzel
Peter-Michael
PM
Gurka
Stephanie
S
Kroczek
Richard A
RA
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
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