Rapamycin enhances the number of alloantigen-induced human CD103+CD8+ regulatory T cells in vitro
Regulatory T cells (T(reg) cells) may be operational in both the induction and maintenance of transplantation tolerance. We recently showed that alloantigen-induced CD103+ CD8+ T cells strongly suppressed T-cell proliferation in mixed lymphocyte culture (MLC) via a contact-dependent mechanism. CD103...
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Veröffentlicht in: | Transplantation 2007-04, Vol.83 (8), p.1098-1106 |
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description | Regulatory T cells (T(reg) cells) may be operational in both the induction and maintenance of transplantation tolerance. We recently showed that alloantigen-induced CD103+ CD8+ T cells strongly suppressed T-cell proliferation in mixed lymphocyte culture (MLC) via a contact-dependent mechanism. CD103 directs T lymphocytes to their ligand E-cadherin, which is expressed on renal tubular epithelial cells, and CD103+ CD8+ T cells have been described to be present in late renal allograft rejection.
We studied the influence of prednisolone, cyclosporin, tacrolimus, CD25 monoclonal antibodies, rapamycin, and mycophenolate mofetil (MMF) on the development and functional activity of alloantigen-activated CD103+ CD8+ T cells in MLC.
Calcineurin inhibitors, MMF, and CD25mAb did not influence the number of CD103 expressing CD8+ T cells. In contrast, corticosteroids diminished CD103 expression on alloactivated CD8+ T cells, which appeared to be caused by their inhibitory action on myeloid dendritic cells. Addition of rapamycin to allocultures led to an increased percentage of CD103+ CD8+ alloreactive T cells. Moreover, in the presence of rapamycin, these cells tended to show higher suppressive capacity.
Alloreactive CD103+ CD8+ T(reg) cells may expand and exert their suppressive function during immunosuppressive treatment with rapamycin. These data are relevant in the design of immunosuppressive drug regimens intended to induce and/or maintain transplantation tolerance. |
doi_str_mv | 10.1097/01.tp.0000259555.29762.f0 |
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We studied the influence of prednisolone, cyclosporin, tacrolimus, CD25 monoclonal antibodies, rapamycin, and mycophenolate mofetil (MMF) on the development and functional activity of alloantigen-activated CD103+ CD8+ T cells in MLC.
Calcineurin inhibitors, MMF, and CD25mAb did not influence the number of CD103 expressing CD8+ T cells. In contrast, corticosteroids diminished CD103 expression on alloactivated CD8+ T cells, which appeared to be caused by their inhibitory action on myeloid dendritic cells. Addition of rapamycin to allocultures led to an increased percentage of CD103+ CD8+ alloreactive T cells. Moreover, in the presence of rapamycin, these cells tended to show higher suppressive capacity.
Alloreactive CD103+ CD8+ T(reg) cells may expand and exert their suppressive function during immunosuppressive treatment with rapamycin. These data are relevant in the design of immunosuppressive drug regimens intended to induce and/or maintain transplantation tolerance.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/01.tp.0000259555.29762.f0</identifier><identifier>PMID: 17452901</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Antibacterial agents ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antigens, CD - immunology ; Biological and medical sciences ; Calcineurin - metabolism ; Calcineurin Inhibitors ; CD8-Positive T-Lymphocytes - cytology ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Dendritic Cells - drug effects ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Fundamental and applied biological sciences. Psychology ; Fundamental immunology ; Humans ; Integrin alpha Chains - immunology ; Isoantigens - immunology ; Medical sciences ; Pharmacology. Drug treatments ; Prednisolone - pharmacology ; Sirolimus - pharmacology ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Tissue, organ and graft immunology</subject><ispartof>Transplantation, 2007-04, Vol.83 (8), p.1098-1106</ispartof><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c396t-5d33442d05ffc27e4aadc2ea7b2d4cef0f669145d2e4bfd22f200970821b88e53</citedby><cites>FETCH-LOGICAL-c396t-5d33442d05ffc27e4aadc2ea7b2d4cef0f669145d2e4bfd22f200970821b88e53</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=18715495$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17452901$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>USS, Elena</creatorcontrib><creatorcontrib>YONG, Si-La</creatorcontrib><creatorcontrib>HOOIBRINK, Berend</creatorcontrib><creatorcontrib>VAN LIER, Rene A. W</creatorcontrib><creatorcontrib>TEN BERG, Ineke J. M</creatorcontrib><title>Rapamycin enhances the number of alloantigen-induced human CD103+CD8+ regulatory T cells in vitro</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Regulatory T cells (T(reg) cells) may be operational in both the induction and maintenance of transplantation tolerance. We recently showed that alloantigen-induced CD103+ CD8+ T cells strongly suppressed T-cell proliferation in mixed lymphocyte culture (MLC) via a contact-dependent mechanism. CD103 directs T lymphocytes to their ligand E-cadherin, which is expressed on renal tubular epithelial cells, and CD103+ CD8+ T cells have been described to be present in late renal allograft rejection.
We studied the influence of prednisolone, cyclosporin, tacrolimus, CD25 monoclonal antibodies, rapamycin, and mycophenolate mofetil (MMF) on the development and functional activity of alloantigen-activated CD103+ CD8+ T cells in MLC.
Calcineurin inhibitors, MMF, and CD25mAb did not influence the number of CD103 expressing CD8+ T cells. In contrast, corticosteroids diminished CD103 expression on alloactivated CD8+ T cells, which appeared to be caused by their inhibitory action on myeloid dendritic cells. Addition of rapamycin to allocultures led to an increased percentage of CD103+ CD8+ alloreactive T cells. Moreover, in the presence of rapamycin, these cells tended to show higher suppressive capacity.
Alloreactive CD103+ CD8+ T(reg) cells may expand and exert their suppressive function during immunosuppressive treatment with rapamycin. These data are relevant in the design of immunosuppressive drug regimens intended to induce and/or maintain transplantation tolerance.</description><subject>Antibacterial agents</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antigens, CD - immunology</subject><subject>Biological and medical sciences</subject><subject>Calcineurin - metabolism</subject><subject>Calcineurin Inhibitors</subject><subject>CD8-Positive T-Lymphocytes - cytology</subject><subject>CD8-Positive T-Lymphocytes - drug effects</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>CD8-Positive T-Lymphocytes - metabolism</subject><subject>Cell Differentiation</subject><subject>Cell Proliferation</subject><subject>Cells, Cultured</subject><subject>Dendritic Cells - drug effects</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Fundamental immunology</subject><subject>Humans</subject><subject>Integrin alpha Chains - immunology</subject><subject>Isoantigens - immunology</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Prednisolone - pharmacology</subject><subject>Sirolimus - pharmacology</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Tissue, organ and graft immunology</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1v1DAQhi0EotvCX0DmAJcqYfwVx0e0hYJUCQmVs-XY425Q4gQ7Qdp_T5autHOZy_O-M3oIec-gZmD0J2D1MtewDVdGKVVzoxteR3hBdkwJWTXQwkuyA5CsYkLoK3Jdyu-NV0Lr1-SKaam4AbYj7qeb3Xj0faKYDi55LHQ5IE3r2GGmU6RuGCaXlv4JU9WnsHoM9LCOLtH9HQNxu79rb2nGp3Vwy5SP9JF6HIZCt8a__ZKnN-RVdEPBt-d9Q359_fK4_1Y9_Lj_vv_8UHlhmqVSQQgpeQAVo-capXPBc3S640F6jBCbxjCpAkfZxcB55LC5gJazrm1RiRvy8bl3ztOfFctix76cXnEJp7VYZhojuIANNM-gz1MpGaOdcz-6fLQM7MmvBWaX2V782v9-bTxl352PrN2I4ZI8C92AD2fAFe-GmDelfblwrWZKGiX-AWuwg-E</recordid><startdate>20070427</startdate><enddate>20070427</enddate><creator>USS, Elena</creator><creator>YONG, Si-La</creator><creator>HOOIBRINK, Berend</creator><creator>VAN LIER, Rene A. W</creator><creator>TEN BERG, Ineke J. M</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></search><sort><creationdate>20070427</creationdate><title>Rapamycin enhances the number of alloantigen-induced human CD103+CD8+ regulatory T cells in vitro</title><author>USS, Elena ; YONG, Si-La ; HOOIBRINK, Berend ; VAN LIER, Rene A. W ; TEN BERG, Ineke J. M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c396t-5d33442d05ffc27e4aadc2ea7b2d4cef0f669145d2e4bfd22f200970821b88e53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Antibacterial agents</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antigens, CD - immunology</topic><topic>Biological and medical sciences</topic><topic>Calcineurin - metabolism</topic><topic>Calcineurin Inhibitors</topic><topic>CD8-Positive T-Lymphocytes - cytology</topic><topic>CD8-Positive T-Lymphocytes - drug effects</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cell Differentiation</topic><topic>Cell Proliferation</topic><topic>Cells, Cultured</topic><topic>Dendritic Cells - drug effects</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Fundamental immunology</topic><topic>Humans</topic><topic>Integrin alpha Chains - immunology</topic><topic>Isoantigens - immunology</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Prednisolone - pharmacology</topic><topic>Sirolimus - pharmacology</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Tissue, organ and graft immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>USS, Elena</creatorcontrib><creatorcontrib>YONG, Si-La</creatorcontrib><creatorcontrib>HOOIBRINK, Berend</creatorcontrib><creatorcontrib>VAN LIER, Rene A. W</creatorcontrib><creatorcontrib>TEN BERG, Ineke J. M</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><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>USS, Elena</au><au>YONG, Si-La</au><au>HOOIBRINK, Berend</au><au>VAN LIER, Rene A. W</au><au>TEN BERG, Ineke J. M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Rapamycin enhances the number of alloantigen-induced human CD103+CD8+ regulatory T cells in vitro</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2007-04-27</date><risdate>2007</risdate><volume>83</volume><issue>8</issue><spage>1098</spage><epage>1106</epage><pages>1098-1106</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Regulatory T cells (T(reg) cells) may be operational in both the induction and maintenance of transplantation tolerance. We recently showed that alloantigen-induced CD103+ CD8+ T cells strongly suppressed T-cell proliferation in mixed lymphocyte culture (MLC) via a contact-dependent mechanism. CD103 directs T lymphocytes to their ligand E-cadherin, which is expressed on renal tubular epithelial cells, and CD103+ CD8+ T cells have been described to be present in late renal allograft rejection.
We studied the influence of prednisolone, cyclosporin, tacrolimus, CD25 monoclonal antibodies, rapamycin, and mycophenolate mofetil (MMF) on the development and functional activity of alloantigen-activated CD103+ CD8+ T cells in MLC.
Calcineurin inhibitors, MMF, and CD25mAb did not influence the number of CD103 expressing CD8+ T cells. In contrast, corticosteroids diminished CD103 expression on alloactivated CD8+ T cells, which appeared to be caused by their inhibitory action on myeloid dendritic cells. Addition of rapamycin to allocultures led to an increased percentage of CD103+ CD8+ alloreactive T cells. Moreover, in the presence of rapamycin, these cells tended to show higher suppressive capacity.
Alloreactive CD103+ CD8+ T(reg) cells may expand and exert their suppressive function during immunosuppressive treatment with rapamycin. These data are relevant in the design of immunosuppressive drug regimens intended to induce and/or maintain transplantation tolerance.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>17452901</pmid><doi>10.1097/01.tp.0000259555.29762.f0</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Antibacterial agents Antibiotics. Antiinfectious agents. Antiparasitic agents Antigens, CD - immunology Biological and medical sciences Calcineurin - metabolism Calcineurin Inhibitors CD8-Positive T-Lymphocytes - cytology CD8-Positive T-Lymphocytes - drug effects CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Differentiation Cell Proliferation Cells, Cultured Dendritic Cells - drug effects Dendritic Cells - immunology Dendritic Cells - metabolism Fundamental and applied biological sciences. Psychology Fundamental immunology Humans Integrin alpha Chains - immunology Isoantigens - immunology Medical sciences Pharmacology. Drug treatments Prednisolone - pharmacology Sirolimus - pharmacology Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Tissue, organ and graft immunology |
title | Rapamycin enhances the number of alloantigen-induced human CD103+CD8+ regulatory T cells in vitro |
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