Immunosuppressive and trafficking properties of donor splenic and bone marrow dendritic cells
Infusion of donor dendritic cells (DC) has been shown to prolong allograft survival in a number of models. However, many regimens that utilize donor DC do not consistently produced tolerance or long-term allograft survival. We hypothesized that one factor limiting the therapeutic effect of donor DC...
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| Veröffentlicht in: | Transplantation 2006-02, Vol.81 (3), p.455-462 |
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| creator | EMMANOUILIDIS, Nikos ZHONG GUO YING DONG NEWTON-WEST, Marvin ADAMS, Andrew B HAN LEE, Eun D JUN WANG PEARSON, Thomas C LARSEN, Christian P NEWELL, Kenneth A |
| description | Infusion of donor dendritic cells (DC) has been shown to prolong allograft survival in a number of models. However, many regimens that utilize donor DC do not consistently produced tolerance or long-term allograft survival. We hypothesized that one factor limiting the therapeutic effect of donor DC is their relative inability to traffic to recipient peripheral lymph nodes and inhibit the function of resident alloreactive T cells.
Donor strain DC isolated from the spleens or bone marrow of Flt3L-treated mice were transferred intravenously into recipients at the time of skin grafting. Where indicated, recipients were treated with an anti-CD40L antibody and CTLA4-Ig.
Infusion of donor DC together with costimulatory blockade promoted donor-specific prolongation of skin allograft survival in mice. Perhaps due to their more immature phenotype, bone marrow DC trafficked more effectively to the spleen, bone marrow, and thymus and were associated with significantly longer allograft survival than were splenic DC. Neither population of DC trafficked well to peripheral lymph nodes. Consistent with our hypothesis, splenic but not lymph node T cells from DC-treated recipients displayed donor-specific hyporesponsiveness in vitro.
These data suggest that one factor contributing to rejection following treatment with donor DC plus costimulation blockade is the persistence of donor-reactive T cells within the recipient's secondary lymphoid structures. Strategies to improve DC trafficking to these structures may enhance their therapeutic effect. |
| doi_str_mv | 10.1097/01.tp.0000195779.01491.4e |
| format | Article |
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Donor strain DC isolated from the spleens or bone marrow of Flt3L-treated mice were transferred intravenously into recipients at the time of skin grafting. Where indicated, recipients were treated with an anti-CD40L antibody and CTLA4-Ig.
Infusion of donor DC together with costimulatory blockade promoted donor-specific prolongation of skin allograft survival in mice. Perhaps due to their more immature phenotype, bone marrow DC trafficked more effectively to the spleen, bone marrow, and thymus and were associated with significantly longer allograft survival than were splenic DC. Neither population of DC trafficked well to peripheral lymph nodes. Consistent with our hypothesis, splenic but not lymph node T cells from DC-treated recipients displayed donor-specific hyporesponsiveness in vitro.
These data suggest that one factor contributing to rejection following treatment with donor DC plus costimulation blockade is the persistence of donor-reactive T cells within the recipient's secondary lymphoid structures. Strategies to improve DC trafficking to these structures may enhance their therapeutic effect.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/01.tp.0000195779.01491.4e</identifier><identifier>PMID: 16477234</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Animals ; Biological and medical sciences ; Bone Marrow Cells - immunology ; Cell Movement - immunology ; Dendritic Cells - immunology ; Dendritic Cells - transplantation ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Graft Enhancement, Immunologic ; Graft Rejection - therapy ; Graft Survival - immunology ; Isoantigens - immunology ; Lymph Nodes - cytology ; Male ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Skin Transplantation - immunology ; Spleen - cytology ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; T-Lymphocytes - immunology ; Tissue, organ and graft immunology ; Transplantation, Homologous</subject><ispartof>Transplantation, 2006-02, Vol.81 (3), p.455-462</ispartof><rights>2006 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-24f03b5d11b5ea4d0f8e7acf5713fe5b1519368779c940e6019c12602250dcad3</citedby><cites>FETCH-LOGICAL-c456t-24f03b5d11b5ea4d0f8e7acf5713fe5b1519368779c940e6019c12602250dcad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17528553$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16477234$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>EMMANOUILIDIS, Nikos</creatorcontrib><creatorcontrib>ZHONG GUO</creatorcontrib><creatorcontrib>YING DONG</creatorcontrib><creatorcontrib>NEWTON-WEST, Marvin</creatorcontrib><creatorcontrib>ADAMS, Andrew B</creatorcontrib><creatorcontrib>HAN LEE, Eun D</creatorcontrib><creatorcontrib>JUN WANG</creatorcontrib><creatorcontrib>PEARSON, Thomas C</creatorcontrib><creatorcontrib>LARSEN, Christian P</creatorcontrib><creatorcontrib>NEWELL, Kenneth A</creatorcontrib><title>Immunosuppressive and trafficking properties of donor splenic and bone marrow dendritic cells</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Infusion of donor dendritic cells (DC) has been shown to prolong allograft survival in a number of models. However, many regimens that utilize donor DC do not consistently produced tolerance or long-term allograft survival. We hypothesized that one factor limiting the therapeutic effect of donor DC is their relative inability to traffic to recipient peripheral lymph nodes and inhibit the function of resident alloreactive T cells.
Donor strain DC isolated from the spleens or bone marrow of Flt3L-treated mice were transferred intravenously into recipients at the time of skin grafting. Where indicated, recipients were treated with an anti-CD40L antibody and CTLA4-Ig.
Infusion of donor DC together with costimulatory blockade promoted donor-specific prolongation of skin allograft survival in mice. Perhaps due to their more immature phenotype, bone marrow DC trafficked more effectively to the spleen, bone marrow, and thymus and were associated with significantly longer allograft survival than were splenic DC. Neither population of DC trafficked well to peripheral lymph nodes. Consistent with our hypothesis, splenic but not lymph node T cells from DC-treated recipients displayed donor-specific hyporesponsiveness in vitro.
These data suggest that one factor contributing to rejection following treatment with donor DC plus costimulation blockade is the persistence of donor-reactive T cells within the recipient's secondary lymphoid structures. Strategies to improve DC trafficking to these structures may enhance their therapeutic effect.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone Marrow Cells - immunology</subject><subject>Cell Movement - immunology</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - transplantation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Graft Enhancement, Immunologic</subject><subject>Graft Rejection - therapy</subject><subject>Graft Survival - immunology</subject><subject>Isoantigens - immunology</subject><subject>Lymph Nodes - cytology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Inbred C57BL</subject><subject>Skin Transplantation - immunology</subject><subject>Spleen - cytology</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>T-Lymphocytes - immunology</subject><subject>Tissue, organ and graft immunology</subject><subject>Transplantation, Homologous</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1TAQhi0EoofCK6CwgF3CTGzH8RJVXCpV6oYuK8txxsiQxMFOQH37uu2RzrKzmcV8c_nnZ-wDQoOg1WfAZlsbKIFaKqUbQKGxEfSCHVByUXfQw0t2ABBYI-fqjL3J-XfhJVfqNTvDTijVcnFgt5fzvC8x7-uaKOfwjyq7jNWWrPfB_QnLr2pNcaW0BcpV9NUYl5iqvE60BPfIDnGharYpxf_VSMuYwlYqjqYpv2WvvJ0yvTvmc3bz7evPix_11fX3y4svV7UTstvqVnjggxwRB0lWjOB7UtZ5qZB7kgNK1Lzri1KnBVBXZDtsO2hbCaOzIz9nn57mllv_7pQ3M4f8cIFdKO7ZdKqTGnj_LIgKdNsKKKB-Al2KOSfyZk2hiLwzCObBBANottWcTDCPJhhBpff9cck-zDSeOo9fL8DHI2Czs5NPdnEhnzgl215Kzu8BaSiRig</recordid><startdate>20060215</startdate><enddate>20060215</enddate><creator>EMMANOUILIDIS, Nikos</creator><creator>ZHONG GUO</creator><creator>YING DONG</creator><creator>NEWTON-WEST, Marvin</creator><creator>ADAMS, Andrew B</creator><creator>HAN LEE, Eun D</creator><creator>JUN WANG</creator><creator>PEARSON, Thomas C</creator><creator>LARSEN, Christian P</creator><creator>NEWELL, Kenneth A</creator><general>Lippincott</general><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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20060215</creationdate><title>Immunosuppressive and trafficking properties of donor splenic and bone marrow dendritic cells</title><author>EMMANOUILIDIS, Nikos ; ZHONG GUO ; YING DONG ; NEWTON-WEST, Marvin ; ADAMS, Andrew B ; HAN LEE, Eun D ; JUN WANG ; PEARSON, Thomas C ; LARSEN, Christian P ; NEWELL, Kenneth A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-24f03b5d11b5ea4d0f8e7acf5713fe5b1519368779c940e6019c12602250dcad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone Marrow Cells - immunology</topic><topic>Cell Movement - immunology</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - transplantation</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Graft Enhancement, Immunologic</topic><topic>Graft Rejection - therapy</topic><topic>Graft Survival - immunology</topic><topic>Isoantigens - immunology</topic><topic>Lymph Nodes - cytology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Inbred C57BL</topic><topic>Skin Transplantation - immunology</topic><topic>Spleen - cytology</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>T-Lymphocytes - immunology</topic><topic>Tissue, organ and graft immunology</topic><topic>Transplantation, Homologous</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>EMMANOUILIDIS, Nikos</creatorcontrib><creatorcontrib>ZHONG GUO</creatorcontrib><creatorcontrib>YING DONG</creatorcontrib><creatorcontrib>NEWTON-WEST, Marvin</creatorcontrib><creatorcontrib>ADAMS, Andrew B</creatorcontrib><creatorcontrib>HAN LEE, Eun D</creatorcontrib><creatorcontrib>JUN WANG</creatorcontrib><creatorcontrib>PEARSON, Thomas C</creatorcontrib><creatorcontrib>LARSEN, Christian P</creatorcontrib><creatorcontrib>NEWELL, Kenneth A</creatorcontrib><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>EMMANOUILIDIS, Nikos</au><au>ZHONG GUO</au><au>YING DONG</au><au>NEWTON-WEST, Marvin</au><au>ADAMS, Andrew B</au><au>HAN LEE, Eun D</au><au>JUN WANG</au><au>PEARSON, Thomas C</au><au>LARSEN, Christian P</au><au>NEWELL, Kenneth A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunosuppressive and trafficking properties of donor splenic and bone marrow dendritic cells</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2006-02-15</date><risdate>2006</risdate><volume>81</volume><issue>3</issue><spage>455</spage><epage>462</epage><pages>455-462</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Infusion of donor dendritic cells (DC) has been shown to prolong allograft survival in a number of models. However, many regimens that utilize donor DC do not consistently produced tolerance or long-term allograft survival. We hypothesized that one factor limiting the therapeutic effect of donor DC is their relative inability to traffic to recipient peripheral lymph nodes and inhibit the function of resident alloreactive T cells.
Donor strain DC isolated from the spleens or bone marrow of Flt3L-treated mice were transferred intravenously into recipients at the time of skin grafting. Where indicated, recipients were treated with an anti-CD40L antibody and CTLA4-Ig.
Infusion of donor DC together with costimulatory blockade promoted donor-specific prolongation of skin allograft survival in mice. Perhaps due to their more immature phenotype, bone marrow DC trafficked more effectively to the spleen, bone marrow, and thymus and were associated with significantly longer allograft survival than were splenic DC. Neither population of DC trafficked well to peripheral lymph nodes. Consistent with our hypothesis, splenic but not lymph node T cells from DC-treated recipients displayed donor-specific hyporesponsiveness in vitro.
These data suggest that one factor contributing to rejection following treatment with donor DC plus costimulation blockade is the persistence of donor-reactive T cells within the recipient's secondary lymphoid structures. Strategies to improve DC trafficking to these structures may enhance their therapeutic effect.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>16477234</pmid><doi>10.1097/01.tp.0000195779.01491.4e</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Transplantation, 2006-02, Vol.81 (3), p.455-462 |
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| subjects | Animals Biological and medical sciences Bone Marrow Cells - immunology Cell Movement - immunology Dendritic Cells - immunology Dendritic Cells - transplantation Fundamental and applied biological sciences. Psychology Fundamental immunology Graft Enhancement, Immunologic Graft Rejection - therapy Graft Survival - immunology Isoantigens - immunology Lymph Nodes - cytology Male Medical sciences Mice Mice, Inbred BALB C Mice, Inbred C57BL Skin Transplantation - immunology Spleen - cytology Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases T-Lymphocytes - immunology Tissue, organ and graft immunology Transplantation, Homologous |
| title | Immunosuppressive and trafficking properties of donor splenic and bone marrow dendritic cells |
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