CD137 ligand reverse signaling has multiple functions in human dendritic cells during an adaptive immune response
T cell activation via dendritic cells (DC) is an important step in the adaptive immune response, which requires DC maturation, migration to lymph nodes and presentation of antigen to T cells. CD137 receptor expressed on activated T cells is a potent costimulatory molecule. Here, we investigated the...
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| Veröffentlicht in: | European journal of immunology 2008-04, Vol.38 (4), p.1024-1032 |
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| container_title | European journal of immunology |
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| creator | Lippert, Undine Zachmann, Karolin Ferrari, David M Schwarz, Herbert Brunner, Edgar Latif, A.H.M. Mahbub-ul Neumann, Christine Soruri, Afsaneh |
| description | T cell activation via dendritic cells (DC) is an important step in the adaptive immune response, which requires DC maturation, migration to lymph nodes and presentation of antigen to T cells. CD137 receptor expressed on activated T cells is a potent costimulatory molecule. Here, we investigated the functions of CD137 ligand (CD137L) in human monocyte-derived DC during an immune response. Cross-linking of CD137L on DC leads to cell maturation in an autocrine fashion, mostly via release of TNF-α. Reverse signaling of CD137L also mediates migration of DC via up-regulation of the CCR7 chemokine receptor, demonstrated by an in vivo MIP-3β-dependent SCID mouse migration model. Finally, CD137L-activated DC induce differentiation of human T cells into potent Th1 effectors. Cocultivation of autologous T cells and CD137L-activated DC in an antigen-specific reaction leads to T cell proliferation and the release of IL-12p70 and IFN-γ. These findings deliver new insights into the multiple effects of reverse signaling of CD137L in human DC during the initiation of an adaptive immune response, including the key features of DC maturation, migration and, ultimately, antigen-specific T cell differentiation. |
| doi_str_mv | 10.1002/eji.200737800 |
| format | Article |
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Mahbub-ul ; Neumann, Christine ; Soruri, Afsaneh</creator><creatorcontrib>Lippert, Undine ; Zachmann, Karolin ; Ferrari, David M ; Schwarz, Herbert ; Brunner, Edgar ; Latif, A.H.M. Mahbub-ul ; Neumann, Christine ; Soruri, Afsaneh</creatorcontrib><description>T cell activation via dendritic cells (DC) is an important step in the adaptive immune response, which requires DC maturation, migration to lymph nodes and presentation of antigen to T cells. CD137 receptor expressed on activated T cells is a potent costimulatory molecule. Here, we investigated the functions of CD137 ligand (CD137L) in human monocyte-derived DC during an immune response. Cross-linking of CD137L on DC leads to cell maturation in an autocrine fashion, mostly via release of TNF-α. Reverse signaling of CD137L also mediates migration of DC via up-regulation of the CCR7 chemokine receptor, demonstrated by an in vivo MIP-3β-dependent SCID mouse migration model. Finally, CD137L-activated DC induce differentiation of human T cells into potent Th1 effectors. Cocultivation of autologous T cells and CD137L-activated DC in an antigen-specific reaction leads to T cell proliferation and the release of IL-12p70 and IFN-γ. These findings deliver new insights into the multiple effects of reverse signaling of CD137L in human DC during the initiation of an adaptive immune response, including the key features of DC maturation, migration and, ultimately, antigen-specific T cell differentiation.</description><identifier>ISSN: 0014-2980</identifier><identifier>EISSN: 1521-4141</identifier><identifier>DOI: 10.1002/eji.200737800</identifier><identifier>PMID: 18395851</identifier><language>eng</language><publisher>Weinheim: Wiley-VCH Verlag</publisher><subject>4-1BB Ligand - immunology ; Adaptation, Physiological - immunology ; Animals ; Antigen presentation ; Antigens - immunology ; Biomarkers ; Cell activation ; Cell Differentiation - immunology ; Cell Movement - immunology ; Cell Proliferation ; Cells, Cultured ; Chemotaxis ; Dendritic cells ; Dendritic Cells - cytology ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Dendritic Cells - secretion ; Epitopes - immunology ; Humans ; Mice ; Mice, SCID ; Receptors, CCR7 - immunology ; Receptors, CCR7 - metabolism ; Signal Transduction - immunology ; T cells ; Th1 Cells - immunology ; Tumor Necrosis Factor-alpha - biosynthesis ; Tumor Necrosis Factor-alpha - immunology ; Up-Regulation - immunology</subject><ispartof>European journal of immunology, 2008-04, Vol.38 (4), p.1024-1032</ispartof><rights>Copyright © 2008 WILEY‐VCH Verlag GmbH & Co. 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Mahbub-ul</creatorcontrib><creatorcontrib>Neumann, Christine</creatorcontrib><creatorcontrib>Soruri, Afsaneh</creatorcontrib><title>CD137 ligand reverse signaling has multiple functions in human dendritic cells during an adaptive immune response</title><title>European journal of immunology</title><addtitle>Eur J Immunol</addtitle><description>T cell activation via dendritic cells (DC) is an important step in the adaptive immune response, which requires DC maturation, migration to lymph nodes and presentation of antigen to T cells. CD137 receptor expressed on activated T cells is a potent costimulatory molecule. Here, we investigated the functions of CD137 ligand (CD137L) in human monocyte-derived DC during an immune response. Cross-linking of CD137L on DC leads to cell maturation in an autocrine fashion, mostly via release of TNF-α. Reverse signaling of CD137L also mediates migration of DC via up-regulation of the CCR7 chemokine receptor, demonstrated by an in vivo MIP-3β-dependent SCID mouse migration model. Finally, CD137L-activated DC induce differentiation of human T cells into potent Th1 effectors. Cocultivation of autologous T cells and CD137L-activated DC in an antigen-specific reaction leads to T cell proliferation and the release of IL-12p70 and IFN-γ. These findings deliver new insights into the multiple effects of reverse signaling of CD137L in human DC during the initiation of an adaptive immune response, including the key features of DC maturation, migration and, ultimately, antigen-specific T cell differentiation.</description><subject>4-1BB Ligand - immunology</subject><subject>Adaptation, Physiological - immunology</subject><subject>Animals</subject><subject>Antigen presentation</subject><subject>Antigens - immunology</subject><subject>Biomarkers</subject><subject>Cell activation</subject><subject>Cell Differentiation - immunology</subject><subject>Cell Movement - immunology</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Chemotaxis</subject><subject>Dendritic cells</subject><subject>Dendritic Cells - cytology</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Dendritic Cells - secretion</subject><subject>Epitopes - immunology</subject><subject>Humans</subject><subject>Mice</subject><subject>Mice, SCID</subject><subject>Receptors, CCR7 - immunology</subject><subject>Receptors, CCR7 - metabolism</subject><subject>Signal Transduction - immunology</subject><subject>T cells</subject><subject>Th1 Cells - immunology</subject><subject>Tumor Necrosis Factor-alpha - biosynthesis</subject><subject>Tumor Necrosis Factor-alpha - immunology</subject><subject>Up-Regulation - immunology</subject><issn>0014-2980</issn><issn>1521-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kEFv1DAQRi0EokvhyBV84pYyYyexfUTbAkWVOEDPljceb10lTmonRf33ZLUr4MRpDvO-p5mPsbcIFwggPtJ9vBAASioN8IxtsBFY1Vjjc7YBwLoSRsMZe1XKPQCYtjEv2RlqaRrd4IY9bC9RKt7HvUueZ3qkXIiXuE-uj2nP71zhw9LPceqJhyV1cxxT4THxu2VwiXtKPsc5dryjvi_cL_kQWzfOu2mOj8TjMCyJVneZ1ii9Zi-C6wu9Oc1zdvv56uf2a3Xz_cv19tNN1dWthqpZ3wlUm-B2TmipvUKNmkToQghGBJQemm4nVGhqrbQXQSlod-AlemU6L8_Zh6N3yuPDQmW2QyyHI12icSm2NQhotFnB6gh2eSwlU7BTjoPLTxbBHjq2a8f2T8cr_-4kXnYD-b_0qdQVUEfgV-zp6f82e_Xt-l_1-2MyuNG6fY7F3v4QgBJA61a2jfwNJeKSEQ</recordid><startdate>200804</startdate><enddate>200804</enddate><creator>Lippert, Undine</creator><creator>Zachmann, Karolin</creator><creator>Ferrari, David M</creator><creator>Schwarz, Herbert</creator><creator>Brunner, Edgar</creator><creator>Latif, A.H.M. Mahbub-ul</creator><creator>Neumann, Christine</creator><creator>Soruri, Afsaneh</creator><general>Wiley-VCH Verlag</general><general>WILEY‐VCH Verlag</general><scope>FBQ</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>200804</creationdate><title>CD137 ligand reverse signaling has multiple functions in human dendritic cells during an adaptive immune response</title><author>Lippert, Undine ; Zachmann, Karolin ; Ferrari, David M ; Schwarz, Herbert ; Brunner, Edgar ; Latif, A.H.M. Mahbub-ul ; Neumann, Christine ; Soruri, Afsaneh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4680-5800fe49faba2838d71818e2fcfff92f13d05cb27f54878d2f7706b0d31d79cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>4-1BB Ligand - immunology</topic><topic>Adaptation, Physiological - immunology</topic><topic>Animals</topic><topic>Antigen presentation</topic><topic>Antigens - immunology</topic><topic>Biomarkers</topic><topic>Cell activation</topic><topic>Cell Differentiation - immunology</topic><topic>Cell Movement - immunology</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Chemotaxis</topic><topic>Dendritic cells</topic><topic>Dendritic Cells - cytology</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Dendritic Cells - secretion</topic><topic>Epitopes - immunology</topic><topic>Humans</topic><topic>Mice</topic><topic>Mice, SCID</topic><topic>Receptors, CCR7 - immunology</topic><topic>Receptors, CCR7 - metabolism</topic><topic>Signal Transduction - immunology</topic><topic>T cells</topic><topic>Th1 Cells - immunology</topic><topic>Tumor Necrosis Factor-alpha - biosynthesis</topic><topic>Tumor Necrosis Factor-alpha - immunology</topic><topic>Up-Regulation - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lippert, Undine</creatorcontrib><creatorcontrib>Zachmann, Karolin</creatorcontrib><creatorcontrib>Ferrari, David M</creatorcontrib><creatorcontrib>Schwarz, Herbert</creatorcontrib><creatorcontrib>Brunner, Edgar</creatorcontrib><creatorcontrib>Latif, A.H.M. 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Mahbub-ul</au><au>Neumann, Christine</au><au>Soruri, Afsaneh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD137 ligand reverse signaling has multiple functions in human dendritic cells during an adaptive immune response</atitle><jtitle>European journal of immunology</jtitle><addtitle>Eur J Immunol</addtitle><date>2008-04</date><risdate>2008</risdate><volume>38</volume><issue>4</issue><spage>1024</spage><epage>1032</epage><pages>1024-1032</pages><issn>0014-2980</issn><eissn>1521-4141</eissn><abstract>T cell activation via dendritic cells (DC) is an important step in the adaptive immune response, which requires DC maturation, migration to lymph nodes and presentation of antigen to T cells. CD137 receptor expressed on activated T cells is a potent costimulatory molecule. Here, we investigated the functions of CD137 ligand (CD137L) in human monocyte-derived DC during an immune response. Cross-linking of CD137L on DC leads to cell maturation in an autocrine fashion, mostly via release of TNF-α. Reverse signaling of CD137L also mediates migration of DC via up-regulation of the CCR7 chemokine receptor, demonstrated by an in vivo MIP-3β-dependent SCID mouse migration model. Finally, CD137L-activated DC induce differentiation of human T cells into potent Th1 effectors. Cocultivation of autologous T cells and CD137L-activated DC in an antigen-specific reaction leads to T cell proliferation and the release of IL-12p70 and IFN-γ. These findings deliver new insights into the multiple effects of reverse signaling of CD137L in human DC during the initiation of an adaptive immune response, including the key features of DC maturation, migration and, ultimately, antigen-specific T cell differentiation.</abstract><cop>Weinheim</cop><pub>Wiley-VCH Verlag</pub><pmid>18395851</pmid><doi>10.1002/eji.200737800</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 4-1BB Ligand - immunology Adaptation, Physiological - immunology Animals Antigen presentation Antigens - immunology Biomarkers Cell activation Cell Differentiation - immunology Cell Movement - immunology Cell Proliferation Cells, Cultured Chemotaxis Dendritic cells Dendritic Cells - cytology Dendritic Cells - immunology Dendritic Cells - metabolism Dendritic Cells - secretion Epitopes - immunology Humans Mice Mice, SCID Receptors, CCR7 - immunology Receptors, CCR7 - metabolism Signal Transduction - immunology T cells Th1 Cells - immunology Tumor Necrosis Factor-alpha - biosynthesis Tumor Necrosis Factor-alpha - immunology Up-Regulation - immunology |
| title | CD137 ligand reverse signaling has multiple functions in human dendritic cells during an adaptive immune response |
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