Induction of human NK cell-mediated cytotoxicity by CD40 triggering on antigen presenting cells
Engagement of CD40 on antigen presenting cells (APC) is central to the initiation of cell-mediated immune response. Here, we investigated the ability of CD40 ligation on APC to induce NK cell-mediated cytotoxicity in the human system and the mechanism(s) underlying this process. We showed that APC (...
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| Veröffentlicht in: | Cellular immunology 2003-02, Vol.221 (2), p.81-88 |
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| container_title | Cellular immunology |
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| creator | Sartorius, Rossella D’Apice, Luciana Barba, Pasquale Guardiola, John Santoni, Angela Velotti, Francesca De Berardinis, Piergiuseppe |
| description | Engagement of CD40 on antigen presenting cells (APC) is central to the initiation of cell-mediated immune response. Here, we investigated the ability of CD40 ligation on APC to induce NK cell-mediated cytotoxicity in the human system and the mechanism(s) underlying this process. We showed that APC (consisting in adherent peripheral blood mononuclear cells) (PBMC), pre-stimulated with anti-CD40 monoclonal antibodies and co-cultured with autologous non-adherent PBMC for 5–9 days, induced CD3−/CD56+ NK cell-mediated cytotoxicity as well as CD3+/CD56+ T cell-mediated unrestricted cytotoxic activity. The generation of NK cell-mediated cytotoxicity was independent on cell-to-cell contact between CD40-triggered APC and NK cells. Moreover, we found that IL-12 did not play a role in NK cells induction by anti-CD40 priming, while IL-2 and IL-15 did play a role. Our results provide an insight into the mechanism by which NK cells are activated in peripheral blood and useful informations for therapeutic application of anti-CD40 antibodies. |
| doi_str_mv | 10.1016/S0008-8749(03)00060-1 |
| format | Article |
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Here, we investigated the ability of CD40 ligation on APC to induce NK cell-mediated cytotoxicity in the human system and the mechanism(s) underlying this process. We showed that APC (consisting in adherent peripheral blood mononuclear cells) (PBMC), pre-stimulated with anti-CD40 monoclonal antibodies and co-cultured with autologous non-adherent PBMC for 5–9 days, induced CD3−/CD56+ NK cell-mediated cytotoxicity as well as CD3+/CD56+ T cell-mediated unrestricted cytotoxic activity. The generation of NK cell-mediated cytotoxicity was independent on cell-to-cell contact between CD40-triggered APC and NK cells. Moreover, we found that IL-12 did not play a role in NK cells induction by anti-CD40 priming, while IL-2 and IL-15 did play a role. Our results provide an insight into the mechanism by which NK cells are activated in peripheral blood and useful informations for therapeutic application of anti-CD40 antibodies.</description><identifier>ISSN: 0008-8749</identifier><identifier>EISSN: 1090-2163</identifier><identifier>DOI: 10.1016/S0008-8749(03)00060-1</identifier><identifier>PMID: 12747948</identifier><language>eng</language><publisher>Netherlands: Elsevier Inc</publisher><subject>Antibodies, Monoclonal - immunology ; Antigen-Presenting Cells - immunology ; APC ; CD3 ; CD40 Antigens - immunology ; CD40 Ligand - immunology ; CD56 ; Coculture Techniques ; Cytotoxicity, Immunologic - immunology ; Flow Cytometry ; Humans ; IL-15 ; IL-2 ; Killer Cells, Natural - immunology ; Leukocytes, Mononuclear - immunology ; Lymphocyte Activation - immunology ; Magnetic microbeads ; PBMC ; Tumor immunity ; Vaccines</subject><ispartof>Cellular immunology, 2003-02, Vol.221 (2), p.81-88</ispartof><rights>2003 Elsevier Science (USA)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-14f74f77df3203ffa91a087733e87b016bd85a00dd0b6ffe7fb6ef73040fea863</citedby><cites>FETCH-LOGICAL-c392t-14f74f77df3203ffa91a087733e87b016bd85a00dd0b6ffe7fb6ef73040fea863</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0008-8749(03)00060-1$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12747948$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sartorius, Rossella</creatorcontrib><creatorcontrib>D’Apice, Luciana</creatorcontrib><creatorcontrib>Barba, Pasquale</creatorcontrib><creatorcontrib>Guardiola, John</creatorcontrib><creatorcontrib>Santoni, Angela</creatorcontrib><creatorcontrib>Velotti, Francesca</creatorcontrib><creatorcontrib>De Berardinis, Piergiuseppe</creatorcontrib><title>Induction of human NK cell-mediated cytotoxicity by CD40 triggering on antigen presenting cells</title><title>Cellular immunology</title><addtitle>Cell Immunol</addtitle><description>Engagement of CD40 on antigen presenting cells (APC) is central to the initiation of cell-mediated immune response. Here, we investigated the ability of CD40 ligation on APC to induce NK cell-mediated cytotoxicity in the human system and the mechanism(s) underlying this process. We showed that APC (consisting in adherent peripheral blood mononuclear cells) (PBMC), pre-stimulated with anti-CD40 monoclonal antibodies and co-cultured with autologous non-adherent PBMC for 5–9 days, induced CD3−/CD56+ NK cell-mediated cytotoxicity as well as CD3+/CD56+ T cell-mediated unrestricted cytotoxic activity. The generation of NK cell-mediated cytotoxicity was independent on cell-to-cell contact between CD40-triggered APC and NK cells. Moreover, we found that IL-12 did not play a role in NK cells induction by anti-CD40 priming, while IL-2 and IL-15 did play a role. Our results provide an insight into the mechanism by which NK cells are activated in peripheral blood and useful informations for therapeutic application of anti-CD40 antibodies.</description><subject>Antibodies, Monoclonal - immunology</subject><subject>Antigen-Presenting Cells - immunology</subject><subject>APC</subject><subject>CD3</subject><subject>CD40 Antigens - immunology</subject><subject>CD40 Ligand - immunology</subject><subject>CD56</subject><subject>Coculture Techniques</subject><subject>Cytotoxicity, Immunologic - immunology</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>IL-15</subject><subject>IL-2</subject><subject>Killer Cells, Natural - immunology</subject><subject>Leukocytes, Mononuclear - immunology</subject><subject>Lymphocyte Activation - immunology</subject><subject>Magnetic microbeads</subject><subject>PBMC</subject><subject>Tumor immunity</subject><subject>Vaccines</subject><issn>0008-8749</issn><issn>1090-2163</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtPxCAUhYnR6Pj4CRpWRhfVS-kUujJmfEajC3VNKL2MmJl2BGqcfy_ziC5NSOCS79wL5xByyOCMASvPXwBAZlIU1Qnw01SUkLENMmBQQZazkm-SwS-yQ3ZD-ABgrKhgm-ywXBSiKuSAqPu26U10XUs7S9_7qW7p0wM1OJlkU2ycjthQM49d7L6dcXFO6zkdXRVAo3fjMXrXjmkS6za6MbZ05jFgOqfbRY-wT7asngQ8WO975O3m-nV0lz0-396PLh8zw6s8ZqywIi3RWJ4Dt1ZXTIMUgnOUok7_rRs51ABNA3VpLQpbl2gFhwIsalnyPXK86jvz3WePIaqpC4sX6Ba7PijBc5ELJv8FmRSyGFZ5Aocr0PguBI9Wzbybaj9XDNQiArWMQC38VcDVMgLFku5oPaCvk4N_qrXnCbhYAZj8-HLoVTAOW5Pc9miiajr3z4gfH9aWJQ</recordid><startdate>20030201</startdate><enddate>20030201</enddate><creator>Sartorius, Rossella</creator><creator>D’Apice, Luciana</creator><creator>Barba, Pasquale</creator><creator>Guardiola, John</creator><creator>Santoni, Angela</creator><creator>Velotti, Francesca</creator><creator>De Berardinis, Piergiuseppe</creator><general>Elsevier Inc</general><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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20030201</creationdate><title>Induction of human NK cell-mediated cytotoxicity by CD40 triggering on antigen presenting cells</title><author>Sartorius, Rossella ; D’Apice, Luciana ; Barba, Pasquale ; Guardiola, John ; Santoni, Angela ; Velotti, Francesca ; De Berardinis, Piergiuseppe</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-14f74f77df3203ffa91a087733e87b016bd85a00dd0b6ffe7fb6ef73040fea863</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Antibodies, Monoclonal - immunology</topic><topic>Antigen-Presenting Cells - immunology</topic><topic>APC</topic><topic>CD3</topic><topic>CD40 Antigens - immunology</topic><topic>CD40 Ligand - immunology</topic><topic>CD56</topic><topic>Coculture Techniques</topic><topic>Cytotoxicity, Immunologic - immunology</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>IL-15</topic><topic>IL-2</topic><topic>Killer Cells, Natural - immunology</topic><topic>Leukocytes, Mononuclear - immunology</topic><topic>Lymphocyte Activation - immunology</topic><topic>Magnetic microbeads</topic><topic>PBMC</topic><topic>Tumor immunity</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sartorius, Rossella</creatorcontrib><creatorcontrib>D’Apice, Luciana</creatorcontrib><creatorcontrib>Barba, Pasquale</creatorcontrib><creatorcontrib>Guardiola, John</creatorcontrib><creatorcontrib>Santoni, Angela</creatorcontrib><creatorcontrib>Velotti, Francesca</creatorcontrib><creatorcontrib>De Berardinis, Piergiuseppe</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cellular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sartorius, Rossella</au><au>D’Apice, Luciana</au><au>Barba, Pasquale</au><au>Guardiola, John</au><au>Santoni, Angela</au><au>Velotti, Francesca</au><au>De Berardinis, Piergiuseppe</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of human NK cell-mediated cytotoxicity by CD40 triggering on antigen presenting cells</atitle><jtitle>Cellular immunology</jtitle><addtitle>Cell Immunol</addtitle><date>2003-02-01</date><risdate>2003</risdate><volume>221</volume><issue>2</issue><spage>81</spage><epage>88</epage><pages>81-88</pages><issn>0008-8749</issn><eissn>1090-2163</eissn><abstract>Engagement of CD40 on antigen presenting cells (APC) is central to the initiation of cell-mediated immune response. Here, we investigated the ability of CD40 ligation on APC to induce NK cell-mediated cytotoxicity in the human system and the mechanism(s) underlying this process. We showed that APC (consisting in adherent peripheral blood mononuclear cells) (PBMC), pre-stimulated with anti-CD40 monoclonal antibodies and co-cultured with autologous non-adherent PBMC for 5–9 days, induced CD3−/CD56+ NK cell-mediated cytotoxicity as well as CD3+/CD56+ T cell-mediated unrestricted cytotoxic activity. The generation of NK cell-mediated cytotoxicity was independent on cell-to-cell contact between CD40-triggered APC and NK cells. Moreover, we found that IL-12 did not play a role in NK cells induction by anti-CD40 priming, while IL-2 and IL-15 did play a role. 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| ispartof | Cellular immunology, 2003-02, Vol.221 (2), p.81-88 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Antibodies, Monoclonal - immunology Antigen-Presenting Cells - immunology APC CD3 CD40 Antigens - immunology CD40 Ligand - immunology CD56 Coculture Techniques Cytotoxicity, Immunologic - immunology Flow Cytometry Humans IL-15 IL-2 Killer Cells, Natural - immunology Leukocytes, Mononuclear - immunology Lymphocyte Activation - immunology Magnetic microbeads PBMC Tumor immunity Vaccines |
| title | Induction of human NK cell-mediated cytotoxicity by CD40 triggering on antigen presenting cells |
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