Induction of tolerance in a rat model of laryngeal transplantation
The major limitation preventing expansion of laryngeal transplantation as a therapeutic modality is the necessity of lifelong immunosuppression. In this report, we describe an immunomodulatory strategy for tolerance induction in laryngeal allotransplantation that permits escape from chronic immunosu...
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Veröffentlicht in: | Transplantation 2003-12, Vol.76 (12), p.1763-1766 |
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creator | AKST, Lee M SIEMIONOW, Maria DAN, Olivia IZYCKI, Dariusz STROME, Marshall |
description | The major limitation preventing expansion of laryngeal transplantation as a therapeutic modality is the necessity of lifelong immunosuppression. In this report, we describe an immunomodulatory strategy for tolerance induction in laryngeal allotransplantation that permits escape from chronic immunosuppression.
Larynges were transplanted from Lewis-Brown-Norway (RT1l/n, F1) donors to Lewis (RT1l) recipients. Recipients received 7 days of treatment with tacrolimus and mouse anti-rat alphabeta T-cell-receptor (TCR) monoclonal antibodies. Histology, mixed lymphocyte reaction (MLR), skin grafting, and flow cytometry assessed functional tolerance, efficacy of immunodepletion, and donor-specific chimerism.
All 10 recipients survived until sacrifice at 100 days. Histology suggested functional allograft tolerance. Skin grafting, MLR, and flow cytometry revealed that tolerance is neither donor-specific nor related to systemic immunocompromise.
In this rat laryngeal-transplantation model, functional tolerance was induced under combined tacrolimus and alphabeta TCR protocol. Mechanisms responsible for this tolerance induction require future elucidation. |
doi_str_mv | 10.1097/01.TP.0000100398.39169.5B |
format | Article |
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Larynges were transplanted from Lewis-Brown-Norway (RT1l/n, F1) donors to Lewis (RT1l) recipients. Recipients received 7 days of treatment with tacrolimus and mouse anti-rat alphabeta T-cell-receptor (TCR) monoclonal antibodies. Histology, mixed lymphocyte reaction (MLR), skin grafting, and flow cytometry assessed functional tolerance, efficacy of immunodepletion, and donor-specific chimerism.
All 10 recipients survived until sacrifice at 100 days. Histology suggested functional allograft tolerance. Skin grafting, MLR, and flow cytometry revealed that tolerance is neither donor-specific nor related to systemic immunocompromise.
In this rat laryngeal-transplantation model, functional tolerance was induced under combined tacrolimus and alphabeta TCR protocol. Mechanisms responsible for this tolerance induction require future elucidation.</description><identifier>ISSN: 0041-1337</identifier><identifier>EISSN: 1534-6080</identifier><identifier>DOI: 10.1097/01.TP.0000100398.39169.5B</identifier><identifier>PMID: 14688529</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Animals ; Antibodies, Monoclonal - therapeutic use ; Biological and medical sciences ; Combined surgery. Multiple transplantations ; Graft Survival - drug effects ; Graft Survival - immunology ; Immunosuppression - methods ; Immunosuppressive Agents - therapeutic use ; Larynx - transplantation ; Lymphocyte Culture Test, Mixed ; Medical sciences ; Models, Animal ; Rats ; Rats, Inbred BN ; Rats, Inbred Lew ; Receptors, Antigen, T-Cell - immunology ; Skin Transplantation - immunology ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Tacrolimus - therapeutic use ; Transplantation Conditioning - methods ; Transplantation, Homologous - immunology</subject><ispartof>Transplantation, 2003-12, Vol.76 (12), p.1763-1766</ispartof><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-a75b4a29711e584f855f31f98b2edb4747d6e08a8e547baf707dce56e663dc353</citedby><cites>FETCH-LOGICAL-c425t-a75b4a29711e584f855f31f98b2edb4747d6e08a8e547baf707dce56e663dc353</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15399121$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14688529$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>AKST, Lee M</creatorcontrib><creatorcontrib>SIEMIONOW, Maria</creatorcontrib><creatorcontrib>DAN, Olivia</creatorcontrib><creatorcontrib>IZYCKI, Dariusz</creatorcontrib><creatorcontrib>STROME, Marshall</creatorcontrib><title>Induction of tolerance in a rat model of laryngeal transplantation</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>The major limitation preventing expansion of laryngeal transplantation as a therapeutic modality is the necessity of lifelong immunosuppression. In this report, we describe an immunomodulatory strategy for tolerance induction in laryngeal allotransplantation that permits escape from chronic immunosuppression.
Larynges were transplanted from Lewis-Brown-Norway (RT1l/n, F1) donors to Lewis (RT1l) recipients. Recipients received 7 days of treatment with tacrolimus and mouse anti-rat alphabeta T-cell-receptor (TCR) monoclonal antibodies. Histology, mixed lymphocyte reaction (MLR), skin grafting, and flow cytometry assessed functional tolerance, efficacy of immunodepletion, and donor-specific chimerism.
All 10 recipients survived until sacrifice at 100 days. Histology suggested functional allograft tolerance. Skin grafting, MLR, and flow cytometry revealed that tolerance is neither donor-specific nor related to systemic immunocompromise.
In this rat laryngeal-transplantation model, functional tolerance was induced under combined tacrolimus and alphabeta TCR protocol. Mechanisms responsible for this tolerance induction require future elucidation.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Combined surgery. Multiple transplantations</subject><subject>Graft Survival - drug effects</subject><subject>Graft Survival - immunology</subject><subject>Immunosuppression - methods</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Larynx - transplantation</subject><subject>Lymphocyte Culture Test, Mixed</subject><subject>Medical sciences</subject><subject>Models, Animal</subject><subject>Rats</subject><subject>Rats, Inbred BN</subject><subject>Rats, Inbred Lew</subject><subject>Receptors, Antigen, T-Cell - immunology</subject><subject>Skin Transplantation - immunology</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Tacrolimus - therapeutic use</subject><subject>Transplantation Conditioning - methods</subject><subject>Transplantation, Homologous - immunology</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkLtOwzAUhi0EoqXwCigMsCX4xPeRVlwqVaJDmS3HsVFQmpQ4GXh7HBqpI17O4O8_lw-hO8AZYCUeMWS7bYbjA4yJkhlRwFXGlmdoDozQlGOJz9EcYwopECJm6CqEr8gzIsQlmgHlUrJczdFy3ZSD7au2SVqf9G3tOtNYl1RNYpLO9Mm-LV09_tWm-2k-namTPiLhUJumN2PwGl14Uwd3M9UF-nh53q3e0s3763r1tEktzVmfGsEKanIlAByT1EvGPAGvZJG7sqCCipI7LI10jIrCeIFFaR3jjnNSWsLIAj0c-x669ntwodf7KlhXx0VcOwQtgArJCP8XBJVTzCiOoDqCtmtD6JzXh67axzs1YD2a1hj0bqtPpvWfac2WMXs7DRmKvStPyUltBO4nwARraj96rcKJY0QpyIH8Aji5hlg</recordid><startdate>20031227</startdate><enddate>20031227</enddate><creator>AKST, Lee M</creator><creator>SIEMIONOW, Maria</creator><creator>DAN, Olivia</creator><creator>IZYCKI, Dariusz</creator><creator>STROME, Marshall</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>20031227</creationdate><title>Induction of tolerance in a rat model of laryngeal transplantation</title><author>AKST, Lee M ; SIEMIONOW, Maria ; DAN, Olivia ; IZYCKI, Dariusz ; STROME, Marshall</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c425t-a75b4a29711e584f855f31f98b2edb4747d6e08a8e547baf707dce56e663dc353</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Combined surgery. Multiple transplantations</topic><topic>Graft Survival - drug effects</topic><topic>Graft Survival - immunology</topic><topic>Immunosuppression - methods</topic><topic>Immunosuppressive Agents - therapeutic use</topic><topic>Larynx - transplantation</topic><topic>Lymphocyte Culture Test, Mixed</topic><topic>Medical sciences</topic><topic>Models, Animal</topic><topic>Rats</topic><topic>Rats, Inbred BN</topic><topic>Rats, Inbred Lew</topic><topic>Receptors, Antigen, T-Cell - immunology</topic><topic>Skin Transplantation - immunology</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Tacrolimus - therapeutic use</topic><topic>Transplantation Conditioning - methods</topic><topic>Transplantation, Homologous - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>AKST, Lee M</creatorcontrib><creatorcontrib>SIEMIONOW, Maria</creatorcontrib><creatorcontrib>DAN, Olivia</creatorcontrib><creatorcontrib>IZYCKI, Dariusz</creatorcontrib><creatorcontrib>STROME, Marshall</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>AKST, Lee M</au><au>SIEMIONOW, Maria</au><au>DAN, Olivia</au><au>IZYCKI, Dariusz</au><au>STROME, Marshall</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of tolerance in a rat model of laryngeal transplantation</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2003-12-27</date><risdate>2003</risdate><volume>76</volume><issue>12</issue><spage>1763</spage><epage>1766</epage><pages>1763-1766</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>The major limitation preventing expansion of laryngeal transplantation as a therapeutic modality is the necessity of lifelong immunosuppression. In this report, we describe an immunomodulatory strategy for tolerance induction in laryngeal allotransplantation that permits escape from chronic immunosuppression.
Larynges were transplanted from Lewis-Brown-Norway (RT1l/n, F1) donors to Lewis (RT1l) recipients. Recipients received 7 days of treatment with tacrolimus and mouse anti-rat alphabeta T-cell-receptor (TCR) monoclonal antibodies. Histology, mixed lymphocyte reaction (MLR), skin grafting, and flow cytometry assessed functional tolerance, efficacy of immunodepletion, and donor-specific chimerism.
All 10 recipients survived until sacrifice at 100 days. Histology suggested functional allograft tolerance. Skin grafting, MLR, and flow cytometry revealed that tolerance is neither donor-specific nor related to systemic immunocompromise.
In this rat laryngeal-transplantation model, functional tolerance was induced under combined tacrolimus and alphabeta TCR protocol. Mechanisms responsible for this tolerance induction require future elucidation.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>14688529</pmid><doi>10.1097/01.TP.0000100398.39169.5B</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antibodies, Monoclonal - therapeutic use Biological and medical sciences Combined surgery. Multiple transplantations Graft Survival - drug effects Graft Survival - immunology Immunosuppression - methods Immunosuppressive Agents - therapeutic use Larynx - transplantation Lymphocyte Culture Test, Mixed Medical sciences Models, Animal Rats Rats, Inbred BN Rats, Inbred Lew Receptors, Antigen, T-Cell - immunology Skin Transplantation - immunology Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Tacrolimus - therapeutic use Transplantation Conditioning - methods Transplantation, Homologous - immunology |
title | Induction of tolerance in a rat model of laryngeal transplantation |
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