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 defin...
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| Published in | The Journal of experimental medicine Vol. 207; no. 6; pp. 1273 - 1281 |
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| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
The Rockefeller University Press
07.06.2010
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0022-1007 1540-9538 1540-9538 |
| DOI | 10.1084/jem.20100348 |
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| 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. |
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| AbstractList | 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. 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 Ca 2+ 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. 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.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. |
| Author | Henn, Volker Ebstein, Frédéric Hartung, Evelyn Movassaghi, Kamran Opitz, Corinna Gurka, Stephanie Schaefer, Michael Tannert, Astrid Bachem, Annabell Kloetzel, Peter-Michael Güttler, Steffen Mages, Hans W. Kroczek, Richard A. Salama, Abdulgabar |
| AuthorAffiliation | 2 Institute of Biochemistry, Charité University Hospital, Humboldt University, 10117 Berlin, Germany 1 Molecular Immunology, Robert Koch-Institute, 13353 Berlin, Germany 3 Rudolf-Boehm-Institute of Pharmacology and Toxicology, 04107 Leipzig, Germany 4 Institute of Transfusion Medicine, Charité University Hospital, Humboldt University, 13353 Berlin, Germany |
| AuthorAffiliation_xml | – name: 1 Molecular Immunology, Robert Koch-Institute, 13353 Berlin, Germany – name: 4 Institute of Transfusion Medicine, Charité University Hospital, Humboldt University, 13353 Berlin, Germany – name: 2 Institute of Biochemistry, Charité University Hospital, Humboldt University, 10117 Berlin, Germany – name: 3 Rudolf-Boehm-Institute of Pharmacology and Toxicology, 04107 Leipzig, Germany |
| Author_xml | – sequence: 1 givenname: Annabell surname: Bachem fullname: Bachem, Annabell – sequence: 2 givenname: Steffen surname: Güttler fullname: Güttler, Steffen – sequence: 3 givenname: Evelyn surname: Hartung fullname: Hartung, Evelyn – sequence: 4 givenname: Frédéric surname: Ebstein fullname: Ebstein, Frédéric – sequence: 5 givenname: Michael surname: Schaefer fullname: Schaefer, Michael – sequence: 6 givenname: Astrid surname: Tannert fullname: Tannert, Astrid – sequence: 7 givenname: Abdulgabar surname: Salama fullname: Salama, Abdulgabar – sequence: 8 givenname: Kamran surname: Movassaghi fullname: Movassaghi, Kamran – sequence: 9 givenname: Corinna surname: Opitz fullname: Opitz, Corinna – sequence: 10 givenname: Hans W. surname: Mages fullname: Mages, Hans W. – sequence: 11 givenname: Volker surname: Henn fullname: Henn, Volker – sequence: 12 givenname: Peter-Michael surname: Kloetzel fullname: Kloetzel, Peter-Michael – sequence: 13 givenname: Stephanie surname: Gurka fullname: Gurka, Stephanie – sequence: 14 givenname: Richard A. surname: Kroczek fullname: Kroczek, Richard A. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/20479115$$D View this record in MEDLINE/PubMed |
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| Snippet | In recent years, human dendritic cells (DCs) could be subdivided into CD304+ plasmacytoid DCs (pDCs) and conventional DCs (cDCs), the latter encompassing the... In recent years, human dendritic cells (DCs) could be subdivided into CD304 + plasmacytoid DCs (pDCs) and conventional DCs (cDCs), the latter encompassing the... |
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| SubjectTerms | Animals Antigen Presentation - immunology Calcium Signaling - immunology CD11c Antigen - metabolism CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - immunology Chemotaxis - immunology Cross-Priming - immunology Dendritic Cells - cytology Dendritic Cells - immunology Humans Mice Models, Immunological Phosphoproteins - immunology Receptors, G-Protein-Coupled - metabolism Receptors, IgG - metabolism Solubility Thrombomodulin - metabolism Viral Matrix Proteins - immunology |
| Title | Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells |
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