Immunosuppressive properties of human umbilical cord‐derived mesenchymal stem cells: role of B7‐H1 and IDO
Umbilical cord is a rich source of mesenchymal stromal or stem cells (MSCs) that can be used for developing allogeneic cell therapy to treat intractable diseases. In this report, we present evidence that umbilical cord‐derived MSCs (UCMSCs) possess important immunomodulatory properties that may enab...
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| Veröffentlicht in: | Immunology and cell biology 2010-11, Vol.88 (8), p.795-806 |
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| description | Umbilical cord is a rich source of mesenchymal stromal or stem cells (MSCs) that can be used for developing allogeneic cell therapy to treat intractable diseases. In this report, we present evidence that umbilical cord‐derived MSCs (UCMSCs) possess important immunomodulatory properties that may enable them to survive in an allogeneic environment. UCMSCs do not express human leukocyte antigen (HLA)‐DR and co‐stimulatory molecules CD80 and CD86 that are required for T‐cell activation. More importantly, UCMSCs constitutively express a negative regulator of T‐cell activation, B7‐H1, and its expression is increased after interferon‐γ (IFN‐γ) treatment. In addition, IFN‐γ treatment induced indoleamine 2,3‐dioxygenase (IDO) and HLA‐DR expression in UCMSCs. Neither control nor IFN‐γ‐treated UCMSCs stimulated allogeneic T‐cell proliferation, and both cell populations inhibited third‐party dendritic cell (DC)‐mediated allostimulatory activity. Addition of a B7‐H1‐specific blocking antibody or an IDO inhibitor, 1 methyl tryptophan (1‐MT) abrogated the T‐cell immunosuppressive activity of these cells. Furthermore, UCMSCs prevented the differentiation and maturation of peripheral blood monocyte‐derived DCs, and augmented the generation of regulatory T cells (Tregs) in culture. The immunosuppressive effects of UCMSCs are largely mediated by cell‐to‐cell contact, although some inhibitory activity was observed with cell‐free supernatant. Our study suggests that these immunomodulatory properties of UCMSCs could potentially improve the outcome of allogeneic stem cell therapy. |
| doi_str_mv | 10.1038/icb.2010.47 |
| format | Article |
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In this report, we present evidence that umbilical cord‐derived MSCs (UCMSCs) possess important immunomodulatory properties that may enable them to survive in an allogeneic environment. UCMSCs do not express human leukocyte antigen (HLA)‐DR and co‐stimulatory molecules CD80 and CD86 that are required for T‐cell activation. More importantly, UCMSCs constitutively express a negative regulator of T‐cell activation, B7‐H1, and its expression is increased after interferon‐γ (IFN‐γ) treatment. In addition, IFN‐γ treatment induced indoleamine 2,3‐dioxygenase (IDO) and HLA‐DR expression in UCMSCs. Neither control nor IFN‐γ‐treated UCMSCs stimulated allogeneic T‐cell proliferation, and both cell populations inhibited third‐party dendritic cell (DC)‐mediated allostimulatory activity. Addition of a B7‐H1‐specific blocking antibody or an IDO inhibitor, 1 methyl tryptophan (1‐MT) abrogated the T‐cell immunosuppressive activity of these cells. Furthermore, UCMSCs prevented the differentiation and maturation of peripheral blood monocyte‐derived DCs, and augmented the generation of regulatory T cells (Tregs) in culture. The immunosuppressive effects of UCMSCs are largely mediated by cell‐to‐cell contact, although some inhibitory activity was observed with cell‐free supernatant. Our study suggests that these immunomodulatory properties of UCMSCs could potentially improve the outcome of allogeneic stem cell therapy.</description><identifier>ISSN: 0818-9641</identifier><identifier>EISSN: 1440-1711</identifier><identifier>DOI: 10.1038/icb.2010.47</identifier><identifier>PMID: 20386557</identifier><language>eng</language><publisher>United States: Nature Publishing Group</publisher><subject>Antibodies, Blocking - pharmacology ; Antigens, CD - immunology ; Antigens, CD - metabolism ; B7-H1 Antigen ; B7‐H1 ; Cell Communication - immunology ; Cell Differentiation - drug effects ; Cell Proliferation - drug effects ; Cells, Cultured ; Dendritic Cells - metabolism ; Dendritic Cells - pathology ; Fetal Blood - cytology ; HLA-DR Antigens - genetics ; HLA-DR Antigens - metabolism ; Humans ; Immune Tolerance - drug effects ; indoleamine 2,3‐dioxygenase ; Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics ; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism ; Interferon-gamma - immunology ; Interferon-gamma - metabolism ; Lymphocyte Activation ; Lymphocyte Culture Test, Mixed ; mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Mesenchymal Stromal Cells - immunology ; Mesenchymal Stromal Cells - metabolism ; T-Lymphocytes, Regulatory - metabolism ; T-Lymphocytes, Regulatory - pathology ; Tryptophan - analogs & derivatives ; Tryptophan - pharmacology ; T‐cell immunosuppression ; umbilical cord</subject><ispartof>Immunology and cell biology, 2010-11, Vol.88 (8), p.795-806</ispartof><rights>2010 Australasian Society for Immunology Inc.</rights><rights>Copyright Nature Publishing Group Nov 2010</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4267-7ff77ac5c34335ff1e92b8afcb9dc8673f3fd792c785a85c2998d7bf3c76385e3</citedby><cites>FETCH-LOGICAL-c4267-7ff77ac5c34335ff1e92b8afcb9dc8673f3fd792c785a85c2998d7bf3c76385e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1038%2Ficb.2010.47$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1038%2Ficb.2010.47$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20386557$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tipnis, Shabari</creatorcontrib><creatorcontrib>Viswanathan, Chandra</creatorcontrib><creatorcontrib>Majumdar, Anish S</creatorcontrib><title>Immunosuppressive properties of human umbilical cord‐derived mesenchymal stem cells: role of B7‐H1 and IDO</title><title>Immunology and cell biology</title><addtitle>Immunol Cell Biol</addtitle><description>Umbilical cord is a rich source of mesenchymal stromal or stem cells (MSCs) that can be used for developing allogeneic cell therapy to treat intractable diseases. In this report, we present evidence that umbilical cord‐derived MSCs (UCMSCs) possess important immunomodulatory properties that may enable them to survive in an allogeneic environment. UCMSCs do not express human leukocyte antigen (HLA)‐DR and co‐stimulatory molecules CD80 and CD86 that are required for T‐cell activation. More importantly, UCMSCs constitutively express a negative regulator of T‐cell activation, B7‐H1, and its expression is increased after interferon‐γ (IFN‐γ) treatment. In addition, IFN‐γ treatment induced indoleamine 2,3‐dioxygenase (IDO) and HLA‐DR expression in UCMSCs. Neither control nor IFN‐γ‐treated UCMSCs stimulated allogeneic T‐cell proliferation, and both cell populations inhibited third‐party dendritic cell (DC)‐mediated allostimulatory activity. Addition of a B7‐H1‐specific blocking antibody or an IDO inhibitor, 1 methyl tryptophan (1‐MT) abrogated the T‐cell immunosuppressive activity of these cells. Furthermore, UCMSCs prevented the differentiation and maturation of peripheral blood monocyte‐derived DCs, and augmented the generation of regulatory T cells (Tregs) in culture. The immunosuppressive effects of UCMSCs are largely mediated by cell‐to‐cell contact, although some inhibitory activity was observed with cell‐free supernatant. Our study suggests that these immunomodulatory properties of UCMSCs could potentially improve the outcome of allogeneic stem cell therapy.</description><subject>Antibodies, Blocking - pharmacology</subject><subject>Antigens, CD - immunology</subject><subject>Antigens, CD - metabolism</subject><subject>B7-H1 Antigen</subject><subject>B7‐H1</subject><subject>Cell Communication - immunology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Cells, Cultured</subject><subject>Dendritic Cells - metabolism</subject><subject>Dendritic Cells - pathology</subject><subject>Fetal Blood - cytology</subject><subject>HLA-DR Antigens - genetics</subject><subject>HLA-DR Antigens - metabolism</subject><subject>Humans</subject><subject>Immune Tolerance - drug effects</subject><subject>indoleamine 2,3‐dioxygenase</subject><subject>Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics</subject><subject>Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism</subject><subject>Interferon-gamma - immunology</subject><subject>Interferon-gamma - metabolism</subject><subject>Lymphocyte Activation</subject><subject>Lymphocyte Culture Test, Mixed</subject><subject>mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Mesenchymal Stromal Cells - immunology</subject><subject>Mesenchymal Stromal Cells - metabolism</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>T-Lymphocytes, Regulatory - pathology</subject><subject>Tryptophan - analogs & derivatives</subject><subject>Tryptophan - pharmacology</subject><subject>T‐cell immunosuppression</subject><subject>umbilical cord</subject><issn>0818-9641</issn><issn>1440-1711</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kcFO3DAQhi0EKlvaE3dkiUMPKGDHTsbpjV0KrETFpT1bjjMWQXGS2ptWe-sj9Bl5Ehwt9MCB08xovvk1Mz8hx5ydcybURWvr85ylSsIeWXApWcaB832yYIqrrColPyQfY3xkjEGuxAdymKe5sihgQfq191M_xGkcA8bY_kY6hmHEsGkx0sHRh8mbnk6-brvWmo7aITRPf_81GBLbUI8Re_uw9akVN-ipxa6LX2kYOpzHl5DgW05N39D11f0ncuBMF_HzSzwiP6-__VjdZnf3N-vV5V1mZV5CBs4BGFtYIYUonONY5bUyztZVY1UJwgnXQJVbUIVRhc2rSjVQO2GhFKpAcUS-7HTTMb8mjBvt2zivZnocpqihlFKpslKJPH1DPg5T6NNymkN6EkghZaLOdpQNQ4wBnR5D603Yas707IJOLujZBS0h0ScvmlPtsfnPvr49AWIH_Gk73L6npdffV8s5T7LPPeyUVA</recordid><startdate>201011</startdate><enddate>201011</enddate><creator>Tipnis, Shabari</creator><creator>Viswanathan, Chandra</creator><creator>Majumdar, Anish S</creator><general>Nature Publishing Group</general><general>Blackwell Science Ltd</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>201011</creationdate><title>Immunosuppressive properties of human umbilical cord‐derived mesenchymal stem cells: role of B7‐H1 and IDO</title><author>Tipnis, Shabari ; Viswanathan, Chandra ; Majumdar, Anish S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4267-7ff77ac5c34335ff1e92b8afcb9dc8673f3fd792c785a85c2998d7bf3c76385e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Antibodies, Blocking - pharmacology</topic><topic>Antigens, CD - immunology</topic><topic>Antigens, CD - metabolism</topic><topic>B7-H1 Antigen</topic><topic>B7‐H1</topic><topic>Cell Communication - immunology</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cells, Cultured</topic><topic>Dendritic Cells - metabolism</topic><topic>Dendritic Cells - pathology</topic><topic>Fetal Blood - cytology</topic><topic>HLA-DR Antigens - genetics</topic><topic>HLA-DR Antigens - metabolism</topic><topic>Humans</topic><topic>Immune Tolerance - drug effects</topic><topic>indoleamine 2,3‐dioxygenase</topic><topic>Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics</topic><topic>Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism</topic><topic>Interferon-gamma - immunology</topic><topic>Interferon-gamma - metabolism</topic><topic>Lymphocyte Activation</topic><topic>Lymphocyte Culture Test, Mixed</topic><topic>mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - drug effects</topic><topic>Mesenchymal Stromal Cells - immunology</topic><topic>Mesenchymal Stromal Cells - metabolism</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>T-Lymphocytes, Regulatory - pathology</topic><topic>Tryptophan - analogs & derivatives</topic><topic>Tryptophan - pharmacology</topic><topic>T‐cell immunosuppression</topic><topic>umbilical cord</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tipnis, Shabari</creatorcontrib><creatorcontrib>Viswanathan, Chandra</creatorcontrib><creatorcontrib>Majumdar, Anish S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest - Health & Medical Complete保健、医学与药学数据库</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection (Proquest) (PQ_SDU_P3)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Immunology and cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tipnis, Shabari</au><au>Viswanathan, Chandra</au><au>Majumdar, Anish S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunosuppressive properties of human umbilical cord‐derived mesenchymal stem cells: role of B7‐H1 and IDO</atitle><jtitle>Immunology and cell biology</jtitle><addtitle>Immunol Cell Biol</addtitle><date>2010-11</date><risdate>2010</risdate><volume>88</volume><issue>8</issue><spage>795</spage><epage>806</epage><pages>795-806</pages><issn>0818-9641</issn><eissn>1440-1711</eissn><abstract>Umbilical cord is a rich source of mesenchymal stromal or stem cells (MSCs) that can be used for developing allogeneic cell therapy to treat intractable diseases. In this report, we present evidence that umbilical cord‐derived MSCs (UCMSCs) possess important immunomodulatory properties that may enable them to survive in an allogeneic environment. UCMSCs do not express human leukocyte antigen (HLA)‐DR and co‐stimulatory molecules CD80 and CD86 that are required for T‐cell activation. More importantly, UCMSCs constitutively express a negative regulator of T‐cell activation, B7‐H1, and its expression is increased after interferon‐γ (IFN‐γ) treatment. In addition, IFN‐γ treatment induced indoleamine 2,3‐dioxygenase (IDO) and HLA‐DR expression in UCMSCs. Neither control nor IFN‐γ‐treated UCMSCs stimulated allogeneic T‐cell proliferation, and both cell populations inhibited third‐party dendritic cell (DC)‐mediated allostimulatory activity. Addition of a B7‐H1‐specific blocking antibody or an IDO inhibitor, 1 methyl tryptophan (1‐MT) abrogated the T‐cell immunosuppressive activity of these cells. Furthermore, UCMSCs prevented the differentiation and maturation of peripheral blood monocyte‐derived DCs, and augmented the generation of regulatory T cells (Tregs) in culture. The immunosuppressive effects of UCMSCs are largely mediated by cell‐to‐cell contact, although some inhibitory activity was observed with cell‐free supernatant. Our study suggests that these immunomodulatory properties of UCMSCs could potentially improve the outcome of allogeneic stem cell therapy.</abstract><cop>United States</cop><pub>Nature Publishing Group</pub><pmid>20386557</pmid><doi>10.1038/icb.2010.47</doi><tpages>12</tpages></addata></record> |
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| subjects | Antibodies, Blocking - pharmacology Antigens, CD - immunology Antigens, CD - metabolism B7-H1 Antigen B7‐H1 Cell Communication - immunology Cell Differentiation - drug effects Cell Proliferation - drug effects Cells, Cultured Dendritic Cells - metabolism Dendritic Cells - pathology Fetal Blood - cytology HLA-DR Antigens - genetics HLA-DR Antigens - metabolism Humans Immune Tolerance - drug effects indoleamine 2,3‐dioxygenase Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism Interferon-gamma - immunology Interferon-gamma - metabolism Lymphocyte Activation Lymphocyte Culture Test, Mixed mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Mesenchymal Stromal Cells - immunology Mesenchymal Stromal Cells - metabolism T-Lymphocytes, Regulatory - metabolism T-Lymphocytes, Regulatory - pathology Tryptophan - analogs & derivatives Tryptophan - pharmacology T‐cell immunosuppression umbilical cord |
| title | Immunosuppressive properties of human umbilical cord‐derived mesenchymal stem cells: role of B7‐H1 and IDO |
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