Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin
Summary T‐cell‐depleting strategies are an integral part of immunosuppressive regimens used in the hematological and solid organ transplant setting. Besides prevention of alloreactivity, treatment with rabbit antithymocyte globulin (rATG) has been related to the induction of immunoregulatory T cells...
Gespeichert in:
| Veröffentlicht in: | Transplant international 2012-03, Vol.25 (3), p.302-313 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 313 |
|---|---|
| container_issue | 3 |
| container_start_page | 302 |
| container_title | Transplant international |
| container_volume | 25 |
| creator | Stauch, Diana Yahyazadeh, Ali Bova, Roberta Melloh, Götz-Christian Füldner, Arne Baron, Udo Olek, Sven Göldner, Katrin Weiss, Sascha Pratschke, Johann Kotsch, Katja |
| description | Summary
T‐cell‐depleting strategies are an integral part of immunosuppressive regimens used in the hematological and solid organ transplant setting. Besides prevention of alloreactivity, treatment with rabbit antithymocyte globulin (rATG) has been related to the induction of immunoregulatory T cells (Treg) in vitro and in vivo. To investigate Treg induced by rATG, we prospectively studied the effect of rATG induction therapy in liver‐transplanted recipients in vivo (n = 28). Treg induction was further evaluated by means of Treg‐specific demethylation region (TSDR) analysis within the FOXP3 locus. Whereas no induction of CD4+ CD25highCD127− Treg could be observed by phenotypic analysis, we could demonstrate an induction of TSDR+ T cells within CD4+ T cells exclusively for rATG‐treated patients in the long‐term (day 540) compared with controls (P = NS). Moreover, although in vitro experiments confirm that rATG primarily led to a conversion of CD4+ CD25− into CD4+ CD25+ T cells displaying immunosuppressive capacities, these cells cannot be classified as bona fide Treg based on their FOXP3 demethylation pattern. Consequently, the generation of Treg after rATG co‐incubation in vitro does not reflect the mechanisms of Treg induction in vivo and therefore the potential clinical relevance of these cells for transplant outcome remains to be determined. |
| doi_str_mv | 10.1111/j.1432-2277.2011.01405.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_1020849260</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3958380441</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4365-fc4432ca5928ab8edffb943e88bfd54237ddfa957632f7f3d1f2435c1a88f7e73</originalsourceid><addsrcrecordid>eNpdkc1u1DAUhS0EotPCKyBLbNgk-C-xs2ABFZSRBpDoINhZTmK3Hjx2iB062fPgOJ0yC7ywr3S_c6TjAwDEqMT5vN6VmFFSEMJ5SRDGJcIMVeXhEVidFo_BCjWUFUhwdgbOY9whhIio0FNwRggWAuNmBf6sfT91yQYPg4Ft8Aoa22s46pvJqRTGGW5hp52LUJmkR-js73ynUfk4OOWTutcWMN1qOISkfbLKQeuNm7Tv9OI6BDd3Lls7mAU23c770M1JwxsX2slZ_ww8McpF_fzhvQDfPrzfXn4sNl-u1pdvN0XHaF0VpmM5XKeqhgjVCt0b0zaMaiFa01eMUN73RjUVrykx3NAeG8Jo1WElhOGa0wvw6ug7jOHXpGOSexuXcMrrMEWJEUGCNaRGGX35H7oL05gjZIrXtWiaWrBMvXigpnavezmMdq_GWf773wy8OQJ31un5tMdILj3KnVzqkktdculR3vcoD3L7db1MWV8c9TYmfTjp1fhT1pzySn7_fCXffbreILT5Ia_pXx6IojQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1766899684</pqid></control><display><type>article</type><title>Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Stauch, Diana ; Yahyazadeh, Ali ; Bova, Roberta ; Melloh, Götz-Christian ; Füldner, Arne ; Baron, Udo ; Olek, Sven ; Göldner, Katrin ; Weiss, Sascha ; Pratschke, Johann ; Kotsch, Katja</creator><creatorcontrib>Stauch, Diana ; Yahyazadeh, Ali ; Bova, Roberta ; Melloh, Götz-Christian ; Füldner, Arne ; Baron, Udo ; Olek, Sven ; Göldner, Katrin ; Weiss, Sascha ; Pratschke, Johann ; Kotsch, Katja</creatorcontrib><description>Summary
T‐cell‐depleting strategies are an integral part of immunosuppressive regimens used in the hematological and solid organ transplant setting. Besides prevention of alloreactivity, treatment with rabbit antithymocyte globulin (rATG) has been related to the induction of immunoregulatory T cells (Treg) in vitro and in vivo. To investigate Treg induced by rATG, we prospectively studied the effect of rATG induction therapy in liver‐transplanted recipients in vivo (n = 28). Treg induction was further evaluated by means of Treg‐specific demethylation region (TSDR) analysis within the FOXP3 locus. Whereas no induction of CD4+ CD25highCD127− Treg could be observed by phenotypic analysis, we could demonstrate an induction of TSDR+ T cells within CD4+ T cells exclusively for rATG‐treated patients in the long‐term (day 540) compared with controls (P = NS). Moreover, although in vitro experiments confirm that rATG primarily led to a conversion of CD4+ CD25− into CD4+ CD25+ T cells displaying immunosuppressive capacities, these cells cannot be classified as bona fide Treg based on their FOXP3 demethylation pattern. Consequently, the generation of Treg after rATG co‐incubation in vitro does not reflect the mechanisms of Treg induction in vivo and therefore the potential clinical relevance of these cells for transplant outcome remains to be determined.</description><identifier>ISSN: 0934-0874</identifier><identifier>EISSN: 1432-2277</identifier><identifier>DOI: 10.1111/j.1432-2277.2011.01405.x</identifier><identifier>PMID: 22188119</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Adult ; Animals ; Antilymphocyte serum ; Antilymphocyte Serum - immunology ; Antilymphocyte Serum - therapeutic use ; CD25 antigen ; CD4 antigen ; Demethylation ; End Stage Liver Disease - surgery ; Female ; Flow Cytometry ; Forkhead Transcription Factors - metabolism ; Foxp3 protein ; Graft Rejection - prevention & control ; Hepatocytes ; Humans ; Immunoregulation ; Immunosuppressive agents ; Immunosuppressive Agents - immunology ; Immunosuppressive Agents - therapeutic use ; Liver transplantation ; Liver Transplantation - immunology ; Lymphocyte Activation ; Lymphocytes ; Lymphocytes T ; Male ; Methylation ; Middle Aged ; Rabbits ; rATG induction therapy ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; T-Lymphocytes, Regulatory - metabolism ; thymoglobulin ; Transplantation Conditioning - methods ; Transplants & implants ; Treg</subject><ispartof>Transplant international, 2012-03, Vol.25 (3), p.302-313</ispartof><rights>2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation</rights><rights>2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4365-fc4432ca5928ab8edffb943e88bfd54237ddfa957632f7f3d1f2435c1a88f7e73</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1432-2277.2011.01405.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1432-2277.2011.01405.x$$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/22188119$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Stauch, Diana</creatorcontrib><creatorcontrib>Yahyazadeh, Ali</creatorcontrib><creatorcontrib>Bova, Roberta</creatorcontrib><creatorcontrib>Melloh, Götz-Christian</creatorcontrib><creatorcontrib>Füldner, Arne</creatorcontrib><creatorcontrib>Baron, Udo</creatorcontrib><creatorcontrib>Olek, Sven</creatorcontrib><creatorcontrib>Göldner, Katrin</creatorcontrib><creatorcontrib>Weiss, Sascha</creatorcontrib><creatorcontrib>Pratschke, Johann</creatorcontrib><creatorcontrib>Kotsch, Katja</creatorcontrib><title>Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin</title><title>Transplant international</title><addtitle>Transpl Int</addtitle><description>Summary
T‐cell‐depleting strategies are an integral part of immunosuppressive regimens used in the hematological and solid organ transplant setting. Besides prevention of alloreactivity, treatment with rabbit antithymocyte globulin (rATG) has been related to the induction of immunoregulatory T cells (Treg) in vitro and in vivo. To investigate Treg induced by rATG, we prospectively studied the effect of rATG induction therapy in liver‐transplanted recipients in vivo (n = 28). Treg induction was further evaluated by means of Treg‐specific demethylation region (TSDR) analysis within the FOXP3 locus. Whereas no induction of CD4+ CD25highCD127− Treg could be observed by phenotypic analysis, we could demonstrate an induction of TSDR+ T cells within CD4+ T cells exclusively for rATG‐treated patients in the long‐term (day 540) compared with controls (P = NS). Moreover, although in vitro experiments confirm that rATG primarily led to a conversion of CD4+ CD25− into CD4+ CD25+ T cells displaying immunosuppressive capacities, these cells cannot be classified as bona fide Treg based on their FOXP3 demethylation pattern. Consequently, the generation of Treg after rATG co‐incubation in vitro does not reflect the mechanisms of Treg induction in vivo and therefore the potential clinical relevance of these cells for transplant outcome remains to be determined.</description><subject>Adult</subject><subject>Animals</subject><subject>Antilymphocyte serum</subject><subject>Antilymphocyte Serum - immunology</subject><subject>Antilymphocyte Serum - therapeutic use</subject><subject>CD25 antigen</subject><subject>CD4 antigen</subject><subject>Demethylation</subject><subject>End Stage Liver Disease - surgery</subject><subject>Female</subject><subject>Flow Cytometry</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Foxp3 protein</subject><subject>Graft Rejection - prevention & control</subject><subject>Hepatocytes</subject><subject>Humans</subject><subject>Immunoregulation</subject><subject>Immunosuppressive agents</subject><subject>Immunosuppressive Agents - immunology</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Liver transplantation</subject><subject>Liver Transplantation - immunology</subject><subject>Lymphocyte Activation</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Methylation</subject><subject>Middle Aged</subject><subject>Rabbits</subject><subject>rATG induction therapy</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Retrospective Studies</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><subject>thymoglobulin</subject><subject>Transplantation Conditioning - methods</subject><subject>Transplants & implants</subject><subject>Treg</subject><issn>0934-0874</issn><issn>1432-2277</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1u1DAUhS0EotPCKyBLbNgk-C-xs2ABFZSRBpDoINhZTmK3Hjx2iB062fPgOJ0yC7ywr3S_c6TjAwDEqMT5vN6VmFFSEMJ5SRDGJcIMVeXhEVidFo_BCjWUFUhwdgbOY9whhIio0FNwRggWAuNmBf6sfT91yQYPg4Ft8Aoa22s46pvJqRTGGW5hp52LUJmkR-js73ynUfk4OOWTutcWMN1qOISkfbLKQeuNm7Tv9OI6BDd3Lls7mAU23c770M1JwxsX2slZ_ww8McpF_fzhvQDfPrzfXn4sNl-u1pdvN0XHaF0VpmM5XKeqhgjVCt0b0zaMaiFa01eMUN73RjUVrykx3NAeG8Jo1WElhOGa0wvw6ug7jOHXpGOSexuXcMrrMEWJEUGCNaRGGX35H7oL05gjZIrXtWiaWrBMvXigpnavezmMdq_GWf773wy8OQJ31un5tMdILj3KnVzqkktdculR3vcoD3L7db1MWV8c9TYmfTjp1fhT1pzySn7_fCXffbreILT5Ia_pXx6IojQ</recordid><startdate>201203</startdate><enddate>201203</enddate><creator>Stauch, Diana</creator><creator>Yahyazadeh, Ali</creator><creator>Bova, Roberta</creator><creator>Melloh, Götz-Christian</creator><creator>Füldner, Arne</creator><creator>Baron, Udo</creator><creator>Olek, Sven</creator><creator>Göldner, Katrin</creator><creator>Weiss, Sascha</creator><creator>Pratschke, Johann</creator><creator>Kotsch, Katja</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QO</scope><scope>7T5</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope></search><sort><creationdate>201203</creationdate><title>Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin</title><author>Stauch, Diana ; Yahyazadeh, Ali ; Bova, Roberta ; Melloh, Götz-Christian ; Füldner, Arne ; Baron, Udo ; Olek, Sven ; Göldner, Katrin ; Weiss, Sascha ; Pratschke, Johann ; Kotsch, Katja</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4365-fc4432ca5928ab8edffb943e88bfd54237ddfa957632f7f3d1f2435c1a88f7e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adult</topic><topic>Animals</topic><topic>Antilymphocyte serum</topic><topic>Antilymphocyte Serum - immunology</topic><topic>Antilymphocyte Serum - therapeutic use</topic><topic>CD25 antigen</topic><topic>CD4 antigen</topic><topic>Demethylation</topic><topic>End Stage Liver Disease - surgery</topic><topic>Female</topic><topic>Flow Cytometry</topic><topic>Forkhead Transcription Factors - metabolism</topic><topic>Foxp3 protein</topic><topic>Graft Rejection - prevention & control</topic><topic>Hepatocytes</topic><topic>Humans</topic><topic>Immunoregulation</topic><topic>Immunosuppressive agents</topic><topic>Immunosuppressive Agents - immunology</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Liver transplantation</topic><topic>Liver Transplantation - immunology</topic><topic>Lymphocyte Activation</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Male</topic><topic>Methylation</topic><topic>Middle Aged</topic><topic>Rabbits</topic><topic>rATG induction therapy</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>Retrospective Studies</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><topic>thymoglobulin</topic><topic>Transplantation Conditioning - methods</topic><topic>Transplants & implants</topic><topic>Treg</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Stauch, Diana</creatorcontrib><creatorcontrib>Yahyazadeh, Ali</creatorcontrib><creatorcontrib>Bova, Roberta</creatorcontrib><creatorcontrib>Melloh, Götz-Christian</creatorcontrib><creatorcontrib>Füldner, Arne</creatorcontrib><creatorcontrib>Baron, Udo</creatorcontrib><creatorcontrib>Olek, Sven</creatorcontrib><creatorcontrib>Göldner, Katrin</creatorcontrib><creatorcontrib>Weiss, Sascha</creatorcontrib><creatorcontrib>Pratschke, Johann</creatorcontrib><creatorcontrib>Kotsch, Katja</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Transplant international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Stauch, Diana</au><au>Yahyazadeh, Ali</au><au>Bova, Roberta</au><au>Melloh, Götz-Christian</au><au>Füldner, Arne</au><au>Baron, Udo</au><au>Olek, Sven</au><au>Göldner, Katrin</au><au>Weiss, Sascha</au><au>Pratschke, Johann</au><au>Kotsch, Katja</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin</atitle><jtitle>Transplant international</jtitle><addtitle>Transpl Int</addtitle><date>2012-03</date><risdate>2012</risdate><volume>25</volume><issue>3</issue><spage>302</spage><epage>313</epage><pages>302-313</pages><issn>0934-0874</issn><eissn>1432-2277</eissn><abstract>Summary
T‐cell‐depleting strategies are an integral part of immunosuppressive regimens used in the hematological and solid organ transplant setting. Besides prevention of alloreactivity, treatment with rabbit antithymocyte globulin (rATG) has been related to the induction of immunoregulatory T cells (Treg) in vitro and in vivo. To investigate Treg induced by rATG, we prospectively studied the effect of rATG induction therapy in liver‐transplanted recipients in vivo (n = 28). Treg induction was further evaluated by means of Treg‐specific demethylation region (TSDR) analysis within the FOXP3 locus. Whereas no induction of CD4+ CD25highCD127− Treg could be observed by phenotypic analysis, we could demonstrate an induction of TSDR+ T cells within CD4+ T cells exclusively for rATG‐treated patients in the long‐term (day 540) compared with controls (P = NS). Moreover, although in vitro experiments confirm that rATG primarily led to a conversion of CD4+ CD25− into CD4+ CD25+ T cells displaying immunosuppressive capacities, these cells cannot be classified as bona fide Treg based on their FOXP3 demethylation pattern. Consequently, the generation of Treg after rATG co‐incubation in vitro does not reflect the mechanisms of Treg induction in vivo and therefore the potential clinical relevance of these cells for transplant outcome remains to be determined.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22188119</pmid><doi>10.1111/j.1432-2277.2011.01405.x</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0934-0874 |
| ispartof | Transplant international, 2012-03, Vol.25 (3), p.302-313 |
| issn | 0934-0874 1432-2277 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1020849260 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adult Animals Antilymphocyte serum Antilymphocyte Serum - immunology Antilymphocyte Serum - therapeutic use CD25 antigen CD4 antigen Demethylation End Stage Liver Disease - surgery Female Flow Cytometry Forkhead Transcription Factors - metabolism Foxp3 protein Graft Rejection - prevention & control Hepatocytes Humans Immunoregulation Immunosuppressive agents Immunosuppressive Agents - immunology Immunosuppressive Agents - therapeutic use Liver transplantation Liver Transplantation - immunology Lymphocyte Activation Lymphocytes Lymphocytes T Male Methylation Middle Aged Rabbits rATG induction therapy Real-Time Polymerase Chain Reaction Retrospective Studies T-Lymphocytes, Regulatory - metabolism thymoglobulin Transplantation Conditioning - methods Transplants & implants Treg |
| title | Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T00%3A06%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Induction%20of%20bona%20fide%20regulatory%20T%20cells%20after%20liver%20transplantation%20-%20the%20potential%20influence%20of%20polyclonal%20antithymocyte%20globulin&rft.jtitle=Transplant%20international&rft.au=Stauch,%20Diana&rft.date=2012-03&rft.volume=25&rft.issue=3&rft.spage=302&rft.epage=313&rft.pages=302-313&rft.issn=0934-0874&rft.eissn=1432-2277&rft_id=info:doi/10.1111/j.1432-2277.2011.01405.x&rft_dat=%3Cproquest_pubme%3E3958380441%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1766899684&rft_id=info:pmid/22188119&rfr_iscdi=true |