Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation
To increase (tumor) vaccine efficacy, there is an urgent need for phenotypic and functional characterization of human dendritic cell (DC) subsets residing in lymphoid tissues. In this study we identified and functionally tested 4 human conventional DC (cDC) subsets within skin-draining sentinel lymp...
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| Veröffentlicht in: | Blood 2011-09, Vol.118 (9), p.2502-2510 |
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| creator | van de Ven, Rieneke van den Hout, Mari F.C.M. Lindenberg, Jelle J. Sluijter, Berbel J.R. van Leeuwen, Paul A.M. Lougheed, Sinéad M. Meijer, Sybren van den Tol, M. Petrousjka Scheper, Rik J. de Gruijl, Tanja D. |
| description | To increase (tumor) vaccine efficacy, there is an urgent need for phenotypic and functional characterization of human dendritic cell (DC) subsets residing in lymphoid tissues. In this study we identified and functionally tested 4 human conventional DC (cDC) subsets within skin-draining sentinel lymph nodes (SLNs) from early-stage melanoma patients. These SLNs were all tumor negative and were removed on average 44 days after excision of the primary melanoma. As such, they were considered representative of steady-state conditions. On comparison with skin-migrated cDC, 2 CD1a+ subsets were identified as most likely skin-derived CD11cint Langerhans cells (LC) with intracellular langerin and E-cadherin expression or as CD11chi dermal DCs with variable expression of langerin. Two other CD1a− LN-residing cDC subsets were characterized as CD14−BDCA3hiCD103− and CD14+BDCA3loCD103+, respectively. Whereas the CD1a+ skin-derived subsets displayed greater levels of phenotypic maturation, they were associated with lower levels of inflammatory cytokine release and were inferior in terms of allogeneic T-cell priming and IFNγ induction. Thus, despite their higher maturation state, skin-derived cDCs (and LCs in particular) proved inferior T-cell activators compared with the CD1a− cDC subsets residing in melanoma-draining LNs. These observations should be considered in the design of DC-targeting immunotherapies. |
| doi_str_mv | 10.1182/blood-2011-03-344838 |
| format | Article |
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Petrousjka ; Scheper, Rik J. ; de Gruijl, Tanja D.</creator><creatorcontrib>van de Ven, Rieneke ; van den Hout, Mari F.C.M. ; Lindenberg, Jelle J. ; Sluijter, Berbel J.R. ; van Leeuwen, Paul A.M. ; Lougheed, Sinéad M. ; Meijer, Sybren ; van den Tol, M. Petrousjka ; Scheper, Rik J. ; de Gruijl, Tanja D.</creatorcontrib><description>To increase (tumor) vaccine efficacy, there is an urgent need for phenotypic and functional characterization of human dendritic cell (DC) subsets residing in lymphoid tissues. In this study we identified and functionally tested 4 human conventional DC (cDC) subsets within skin-draining sentinel lymph nodes (SLNs) from early-stage melanoma patients. These SLNs were all tumor negative and were removed on average 44 days after excision of the primary melanoma. As such, they were considered representative of steady-state conditions. On comparison with skin-migrated cDC, 2 CD1a+ subsets were identified as most likely skin-derived CD11cint Langerhans cells (LC) with intracellular langerin and E-cadherin expression or as CD11chi dermal DCs with variable expression of langerin. Two other CD1a− LN-residing cDC subsets were characterized as CD14−BDCA3hiCD103− and CD14+BDCA3loCD103+, respectively. Whereas the CD1a+ skin-derived subsets displayed greater levels of phenotypic maturation, they were associated with lower levels of inflammatory cytokine release and were inferior in terms of allogeneic T-cell priming and IFNγ induction. Thus, despite their higher maturation state, skin-derived cDCs (and LCs in particular) proved inferior T-cell activators compared with the CD1a− cDC subsets residing in melanoma-draining LNs. These observations should be considered in the design of DC-targeting immunotherapies.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2011-03-344838</identifier><identifier>PMID: 21750314</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Antigens, CD - analysis ; Antigens, CD1 - analysis ; Antigens, Surface - analysis ; Biological and medical sciences ; Cadherins - analysis ; CD11c Antigen - analysis ; Dendritic Cells - chemistry ; Dendritic Cells - classification ; Dendritic Cells - immunology ; Flow Cytometry ; Hematologic and hematopoietic diseases ; Humans ; Immunophenotyping ; Integrin alpha Chains - analysis ; Langerhans Cells - chemistry ; Langerhans Cells - immunology ; Lectins, C-Type - analysis ; Lipopolysaccharide Receptors - analysis ; Lymph Nodes - cytology ; Lymph Nodes - immunology ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; Lymphokines - metabolism ; Mannose-Binding Lectins - analysis ; Medical sciences ; Melanoma - immunology ; Melanoma - pathology ; Melanoma - surgery ; Sentinel Lymph Node Biopsy ; Skin - immunology ; Skin Neoplasms - immunology ; Skin Neoplasms - pathology ; Skin Neoplasms - surgery ; T-Lymphocytes - immunology</subject><ispartof>Blood, 2011-09, Vol.118 (9), p.2502-2510</ispartof><rights>2011 American Society of Hematology</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-e1bdcefbe625437699594c680918116e06eddd973982402bc9e8237eb4aa2f9d3</citedby><cites>FETCH-LOGICAL-c437t-e1bdcefbe625437699594c680918116e06eddd973982402bc9e8237eb4aa2f9d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24483998$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21750314$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van de Ven, Rieneke</creatorcontrib><creatorcontrib>van den Hout, Mari F.C.M.</creatorcontrib><creatorcontrib>Lindenberg, Jelle J.</creatorcontrib><creatorcontrib>Sluijter, Berbel J.R.</creatorcontrib><creatorcontrib>van Leeuwen, Paul A.M.</creatorcontrib><creatorcontrib>Lougheed, Sinéad M.</creatorcontrib><creatorcontrib>Meijer, Sybren</creatorcontrib><creatorcontrib>van den Tol, M. Petrousjka</creatorcontrib><creatorcontrib>Scheper, Rik J.</creatorcontrib><creatorcontrib>de Gruijl, Tanja D.</creatorcontrib><title>Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation</title><title>Blood</title><addtitle>Blood</addtitle><description>To increase (tumor) vaccine efficacy, there is an urgent need for phenotypic and functional characterization of human dendritic cell (DC) subsets residing in lymphoid tissues. In this study we identified and functionally tested 4 human conventional DC (cDC) subsets within skin-draining sentinel lymph nodes (SLNs) from early-stage melanoma patients. These SLNs were all tumor negative and were removed on average 44 days after excision of the primary melanoma. As such, they were considered representative of steady-state conditions. On comparison with skin-migrated cDC, 2 CD1a+ subsets were identified as most likely skin-derived CD11cint Langerhans cells (LC) with intracellular langerin and E-cadherin expression or as CD11chi dermal DCs with variable expression of langerin. Two other CD1a− LN-residing cDC subsets were characterized as CD14−BDCA3hiCD103− and CD14+BDCA3loCD103+, respectively. Whereas the CD1a+ skin-derived subsets displayed greater levels of phenotypic maturation, they were associated with lower levels of inflammatory cytokine release and were inferior in terms of allogeneic T-cell priming and IFNγ induction. Thus, despite their higher maturation state, skin-derived cDCs (and LCs in particular) proved inferior T-cell activators compared with the CD1a− cDC subsets residing in melanoma-draining LNs. These observations should be considered in the design of DC-targeting immunotherapies.</description><subject>Antigens, CD - analysis</subject><subject>Antigens, CD1 - analysis</subject><subject>Antigens, Surface - analysis</subject><subject>Biological and medical sciences</subject><subject>Cadherins - analysis</subject><subject>CD11c Antigen - analysis</subject><subject>Dendritic Cells - chemistry</subject><subject>Dendritic Cells - classification</subject><subject>Dendritic Cells - immunology</subject><subject>Flow Cytometry</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Humans</subject><subject>Immunophenotyping</subject><subject>Integrin alpha Chains - analysis</subject><subject>Langerhans Cells - chemistry</subject><subject>Langerhans Cells - immunology</subject><subject>Lectins, C-Type - analysis</subject><subject>Lipopolysaccharide Receptors - analysis</subject><subject>Lymph Nodes - cytology</subject><subject>Lymph Nodes - immunology</subject><subject>Lymphocyte Activation</subject><subject>Lymphocyte Culture Test, Mixed</subject><subject>Lymphokines - metabolism</subject><subject>Mannose-Binding Lectins - analysis</subject><subject>Medical sciences</subject><subject>Melanoma - immunology</subject><subject>Melanoma - pathology</subject><subject>Melanoma - surgery</subject><subject>Sentinel Lymph Node Biopsy</subject><subject>Skin - immunology</subject><subject>Skin Neoplasms - immunology</subject><subject>Skin Neoplasms - pathology</subject><subject>Skin Neoplasms - surgery</subject><subject>T-Lymphocytes - immunology</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEuLFDEURoM4OO3oPxDJRlxF86qqZCNIMz5gYDbjOqSSW3a0KmmTqoaZlT996tHqztWFj3O_ezkIvWL0HWOKv2_7lDzhlDFCBRFSKqGeoB2ruCKUcvoU7SilNZG6YZfoeSk_KGVS8OoZuuSsqahgcod-7w82WzdCDg92DCni1OEuTRm7FE8Ql8j22EP0OYzBYQd9j8vUFhgLDhEfpsFGXH6GSHy2IYb4Hff3w_GAY_KwIhn6rXpM-I6sBfPFcFrDF-iis32Bl-d5hb59ur7bfyE3t5-_7j_eECdFMxJgrXfQtVDzag5qrSstXa2oZoqxGmgN3nvdCK24pLx1GhQXDbTSWt5pL67Q2633mNOvCcpohlCWX2yENBWj1KykYlrNpNxIl1MpGTpzzGGw-d4wahb1ZlVvFvWGCrOpn9denw9M7QD-79If1zPw5gzY4mzfZRtdKP-4pUav9z9sHMw6TgGyKS5AdOBDBjcan8L_P3kEdJeklg</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>van de Ven, Rieneke</creator><creator>van den Hout, Mari F.C.M.</creator><creator>Lindenberg, Jelle J.</creator><creator>Sluijter, Berbel J.R.</creator><creator>van Leeuwen, Paul A.M.</creator><creator>Lougheed, Sinéad M.</creator><creator>Meijer, Sybren</creator><creator>van den Tol, M. Petrousjka</creator><creator>Scheper, Rik J.</creator><creator>de Gruijl, Tanja D.</creator><general>Elsevier Inc</general><general>Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20110901</creationdate><title>Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation</title><author>van de Ven, Rieneke ; van den Hout, Mari F.C.M. ; Lindenberg, Jelle J. ; Sluijter, Berbel J.R. ; van Leeuwen, Paul A.M. ; Lougheed, Sinéad M. ; Meijer, Sybren ; van den Tol, M. Petrousjka ; Scheper, Rik J. ; de Gruijl, Tanja D.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-e1bdcefbe625437699594c680918116e06eddd973982402bc9e8237eb4aa2f9d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Antigens, CD - analysis</topic><topic>Antigens, CD1 - analysis</topic><topic>Antigens, Surface - analysis</topic><topic>Biological and medical sciences</topic><topic>Cadherins - analysis</topic><topic>CD11c Antigen - analysis</topic><topic>Dendritic Cells - chemistry</topic><topic>Dendritic Cells - classification</topic><topic>Dendritic Cells - immunology</topic><topic>Flow Cytometry</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Humans</topic><topic>Immunophenotyping</topic><topic>Integrin alpha Chains - analysis</topic><topic>Langerhans Cells - chemistry</topic><topic>Langerhans Cells - immunology</topic><topic>Lectins, C-Type - analysis</topic><topic>Lipopolysaccharide Receptors - analysis</topic><topic>Lymph Nodes - cytology</topic><topic>Lymph Nodes - immunology</topic><topic>Lymphocyte Activation</topic><topic>Lymphocyte Culture Test, Mixed</topic><topic>Lymphokines - metabolism</topic><topic>Mannose-Binding Lectins - analysis</topic><topic>Medical sciences</topic><topic>Melanoma - immunology</topic><topic>Melanoma - pathology</topic><topic>Melanoma - surgery</topic><topic>Sentinel Lymph Node Biopsy</topic><topic>Skin - immunology</topic><topic>Skin Neoplasms - immunology</topic><topic>Skin Neoplasms - pathology</topic><topic>Skin Neoplasms - surgery</topic><topic>T-Lymphocytes - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van de Ven, Rieneke</creatorcontrib><creatorcontrib>van den Hout, Mari F.C.M.</creatorcontrib><creatorcontrib>Lindenberg, Jelle J.</creatorcontrib><creatorcontrib>Sluijter, Berbel J.R.</creatorcontrib><creatorcontrib>van Leeuwen, Paul A.M.</creatorcontrib><creatorcontrib>Lougheed, Sinéad M.</creatorcontrib><creatorcontrib>Meijer, Sybren</creatorcontrib><creatorcontrib>van den Tol, M. Petrousjka</creatorcontrib><creatorcontrib>Scheper, Rik J.</creatorcontrib><creatorcontrib>de Gruijl, Tanja D.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van de Ven, Rieneke</au><au>van den Hout, Mari F.C.M.</au><au>Lindenberg, Jelle J.</au><au>Sluijter, Berbel J.R.</au><au>van Leeuwen, Paul A.M.</au><au>Lougheed, Sinéad M.</au><au>Meijer, Sybren</au><au>van den Tol, M. Petrousjka</au><au>Scheper, Rik J.</au><au>de Gruijl, Tanja D.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>118</volume><issue>9</issue><spage>2502</spage><epage>2510</epage><pages>2502-2510</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>To increase (tumor) vaccine efficacy, there is an urgent need for phenotypic and functional characterization of human dendritic cell (DC) subsets residing in lymphoid tissues. In this study we identified and functionally tested 4 human conventional DC (cDC) subsets within skin-draining sentinel lymph nodes (SLNs) from early-stage melanoma patients. These SLNs were all tumor negative and were removed on average 44 days after excision of the primary melanoma. As such, they were considered representative of steady-state conditions. On comparison with skin-migrated cDC, 2 CD1a+ subsets were identified as most likely skin-derived CD11cint Langerhans cells (LC) with intracellular langerin and E-cadherin expression or as CD11chi dermal DCs with variable expression of langerin. Two other CD1a− LN-residing cDC subsets were characterized as CD14−BDCA3hiCD103− and CD14+BDCA3loCD103+, respectively. Whereas the CD1a+ skin-derived subsets displayed greater levels of phenotypic maturation, they were associated with lower levels of inflammatory cytokine release and were inferior in terms of allogeneic T-cell priming and IFNγ induction. Thus, despite their higher maturation state, skin-derived cDCs (and LCs in particular) proved inferior T-cell activators compared with the CD1a− cDC subsets residing in melanoma-draining LNs. These observations should be considered in the design of DC-targeting immunotherapies.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>21750314</pmid><doi>10.1182/blood-2011-03-344838</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Antigens, CD - analysis Antigens, CD1 - analysis Antigens, Surface - analysis Biological and medical sciences Cadherins - analysis CD11c Antigen - analysis Dendritic Cells - chemistry Dendritic Cells - classification Dendritic Cells - immunology Flow Cytometry Hematologic and hematopoietic diseases Humans Immunophenotyping Integrin alpha Chains - analysis Langerhans Cells - chemistry Langerhans Cells - immunology Lectins, C-Type - analysis Lipopolysaccharide Receptors - analysis Lymph Nodes - cytology Lymph Nodes - immunology Lymphocyte Activation Lymphocyte Culture Test, Mixed Lymphokines - metabolism Mannose-Binding Lectins - analysis Medical sciences Melanoma - immunology Melanoma - pathology Melanoma - surgery Sentinel Lymph Node Biopsy Skin - immunology Skin Neoplasms - immunology Skin Neoplasms - pathology Skin Neoplasms - surgery T-Lymphocytes - immunology |
| title | Characterization of four conventional dendritic cell subsets in human skin-draining lymph nodes in relation to T-cell activation |
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