Kidney‐Induced Cardiac Allograft Tolerance in Miniature Swine is Dependent on MHC‐Matching of Donor Cardiac and Renal Parenchyma
Kidney allografts possess the ability to enable a short course of immunosuppression to induce tolerance of themselves and of cardiac allografts across a full‐MHC barrier in miniature swine. However, the renal element(s) responsible for kidney‐induced cardiac allograft tolerance (KICAT) are unknown....
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| Veröffentlicht in: | American journal of transplantation 2015-06, Vol.15 (6), p.1580-1590 |
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| creator | Madariaga, M. L. Michel, S. G. La Muraglia, G. M. Sekijima, M. Villani, V. Leonard, D. A. Powell, H. J. Kurtz, J. M. Farkash, E. A. Colvin, R. B. Allan, J. S. Cetrulo, Jr, C. L. Huang, C. A. Sachs, D. H. Yamada, K. Madsen, J. C. |
| description | Kidney allografts possess the ability to enable a short course of immunosuppression to induce tolerance of themselves and of cardiac allografts across a full‐MHC barrier in miniature swine. However, the renal element(s) responsible for kidney‐induced cardiac allograft tolerance (KICAT) are unknown. Here we investigated whether MHC disparities between parenchyma versus hematopoietic‐derived “passenger” cells of the heart and kidney allografts affected KICAT. Heart and kidney allografts were co‐transplanted into MHC‐mismatched recipients treated with high‐dose tacrolimus for 12 days. Group 1 animals (n = 3) received kidney and heart allografts fully MHC‐mismatched to each other and to the recipient. Group 2 animals (n = 3) received kidney and heart allografts MHC‐matched to each other but MHC‐mismatched to the recipient. Group 3 animals (n = 3) received chimeric kidney allografts whose parenchyma was MHC‐mismatched to the donor heart. Group 4 animals (n = 3) received chimeric kidney allografts whose passenger leukocytes were MHC‐mismatched to the donor heart. Five of six heart allografts in Groups 1 and 3 rejected 150 days without rejection (p |
| doi_str_mv | 10.1111/ajt.13131 |
| format | Article |
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Kidney‐induced cardiac allograft tolerance requires MHC‐matching between kidney allograft parenchyma and heart allografts, suggesting that cells intrinsic to the kidney enable cardiac allograft tolerance.</description><identifier>ISSN: 1600-6135</identifier><identifier>EISSN: 1600-6143</identifier><identifier>DOI: 10.1111/ajt.13131</identifier><identifier>PMID: 25824550</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Allografts ; Animals ; basic (laboratory) research / science ; Graft Rejection - immunology ; Graft Rejection - prevention & control ; Heart ; Heart - physiology ; Heart Transplantation ; heart transplantation / cardiology ; Histocompatibility - immunology ; Histocompatibility - physiology ; Immunosuppression Therapy ; Immunosuppressive Agents - therapeutic use ; Kidney - physiology ; Kidney Transplantation ; kidney transplantation / nephrology ; Major Histocompatibility Complex - immunology ; Major Histocompatibility Complex - physiology ; Models, Animal ; Swine ; Swine, Miniature ; Tacrolimus - therapeutic use ; Tissue and Organ Procurement ; tolerance ; tolerance: mechanisms ; Transplantation Tolerance - immunology ; Transplantation Tolerance - physiology</subject><ispartof>American journal of transplantation, 2015-06, Vol.15 (6), p.1580-1590</ispartof><rights>Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons</rights><rights>Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4431-866d6239d5620fb402a85efc1763e05b93d9e67e979635dc60d431e37af4afd13</citedby><cites>FETCH-LOGICAL-c4431-866d6239d5620fb402a85efc1763e05b93d9e67e979635dc60d431e37af4afd13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fajt.13131$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fajt.13131$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25824550$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Madariaga, M. L.</creatorcontrib><creatorcontrib>Michel, S. G.</creatorcontrib><creatorcontrib>La Muraglia, G. M.</creatorcontrib><creatorcontrib>Sekijima, M.</creatorcontrib><creatorcontrib>Villani, V.</creatorcontrib><creatorcontrib>Leonard, D. A.</creatorcontrib><creatorcontrib>Powell, H. J.</creatorcontrib><creatorcontrib>Kurtz, J. M.</creatorcontrib><creatorcontrib>Farkash, E. A.</creatorcontrib><creatorcontrib>Colvin, R. B.</creatorcontrib><creatorcontrib>Allan, J. S.</creatorcontrib><creatorcontrib>Cetrulo, Jr, C. L.</creatorcontrib><creatorcontrib>Huang, C. A.</creatorcontrib><creatorcontrib>Sachs, D. H.</creatorcontrib><creatorcontrib>Yamada, K.</creatorcontrib><creatorcontrib>Madsen, J. C.</creatorcontrib><title>Kidney‐Induced Cardiac Allograft Tolerance in Miniature Swine is Dependent on MHC‐Matching of Donor Cardiac and Renal Parenchyma</title><title>American journal of transplantation</title><addtitle>Am J Transplant</addtitle><description>Kidney allografts possess the ability to enable a short course of immunosuppression to induce tolerance of themselves and of cardiac allografts across a full‐MHC barrier in miniature swine. However, the renal element(s) responsible for kidney‐induced cardiac allograft tolerance (KICAT) are unknown. Here we investigated whether MHC disparities between parenchyma versus hematopoietic‐derived “passenger” cells of the heart and kidney allografts affected KICAT. Heart and kidney allografts were co‐transplanted into MHC‐mismatched recipients treated with high‐dose tacrolimus for 12 days. Group 1 animals (n = 3) received kidney and heart allografts fully MHC‐mismatched to each other and to the recipient. Group 2 animals (n = 3) received kidney and heart allografts MHC‐matched to each other but MHC‐mismatched to the recipient. Group 3 animals (n = 3) received chimeric kidney allografts whose parenchyma was MHC‐mismatched to the donor heart. Group 4 animals (n = 3) received chimeric kidney allografts whose passenger leukocytes were MHC‐mismatched to the donor heart. Five of six heart allografts in Groups 1 and 3 rejected <40 days. In contrast, heart allografts in Groups 2 and 4 survived >150 days without rejection (p < 0.05). These data demonstrate that KICAT requires MHC‐matching between kidney allograft parenchyma and heart allografts, suggesting that cells intrinsic to the kidney enable cardiac allograft tolerance.
Kidney‐induced cardiac allograft tolerance requires MHC‐matching between kidney allograft parenchyma and heart allografts, suggesting that cells intrinsic to the kidney enable cardiac allograft tolerance.</description><subject>Allografts</subject><subject>Animals</subject><subject>basic (laboratory) research / science</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - prevention & control</subject><subject>Heart</subject><subject>Heart - physiology</subject><subject>Heart Transplantation</subject><subject>heart transplantation / cardiology</subject><subject>Histocompatibility - immunology</subject><subject>Histocompatibility - physiology</subject><subject>Immunosuppression Therapy</subject><subject>Immunosuppressive Agents - therapeutic use</subject><subject>Kidney - physiology</subject><subject>Kidney Transplantation</subject><subject>kidney transplantation / nephrology</subject><subject>Major Histocompatibility Complex - immunology</subject><subject>Major Histocompatibility Complex - physiology</subject><subject>Models, Animal</subject><subject>Swine</subject><subject>Swine, Miniature</subject><subject>Tacrolimus - therapeutic use</subject><subject>Tissue and Organ Procurement</subject><subject>tolerance</subject><subject>tolerance: mechanisms</subject><subject>Transplantation Tolerance - immunology</subject><subject>Transplantation Tolerance - physiology</subject><issn>1600-6135</issn><issn>1600-6143</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctuEzEUhkeIipbCghdAltjAIq0vY8_MBilKoRdagSCsrRP7TOLIsVPPDFV2LHiAPiNPgtuUCJCwF7Z8Pn_67VMULxg9Ynkcw7I_YiLPR8UBU5SOFCvF491eyP3iadctKWUVr_mTYp_LmpdS0oPixwdnA25-fr89D3YwaMkEknVgyNj7OE_Q9mQaPSYIBokL5MoFB_2QkHy5cSEfdeQE1xgshp7EXD-bZNkV9GbhwpzElpzEENNOC8GSzxjAk0-QMJjFZgXPir0WfIfPH9bD4uv7d9PJ2ejy4-n5ZHw5MmUp2KhWyiouGisVp-2spBxqia1hlRJI5awRtkFVYVM1SkhrFLX5GooK2hJay8Rh8XbrXQ-zFVqTIyfwep3cCtJGR3D670pwCz2P33QplSybJgtePwhSvB6w6_XKdQa9h4Bx6DRT-V95jqMy-uofdBmHlN99TzFeSyXuEr3ZUibFrkvY7sIwqu96q3Nv9X1vM_vyz_Q78nczM3C8BW6cx83_TXp8Md0qfwFrrLAD</recordid><startdate>201506</startdate><enddate>201506</enddate><creator>Madariaga, M. 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M.</au><au>Farkash, E. A.</au><au>Colvin, R. B.</au><au>Allan, J. S.</au><au>Cetrulo, Jr, C. L.</au><au>Huang, C. A.</au><au>Sachs, D. H.</au><au>Yamada, K.</au><au>Madsen, J. C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Kidney‐Induced Cardiac Allograft Tolerance in Miniature Swine is Dependent on MHC‐Matching of Donor Cardiac and Renal Parenchyma</atitle><jtitle>American journal of transplantation</jtitle><addtitle>Am J Transplant</addtitle><date>2015-06</date><risdate>2015</risdate><volume>15</volume><issue>6</issue><spage>1580</spage><epage>1590</epage><pages>1580-1590</pages><issn>1600-6135</issn><eissn>1600-6143</eissn><abstract>Kidney allografts possess the ability to enable a short course of immunosuppression to induce tolerance of themselves and of cardiac allografts across a full‐MHC barrier in miniature swine. However, the renal element(s) responsible for kidney‐induced cardiac allograft tolerance (KICAT) are unknown. Here we investigated whether MHC disparities between parenchyma versus hematopoietic‐derived “passenger” cells of the heart and kidney allografts affected KICAT. Heart and kidney allografts were co‐transplanted into MHC‐mismatched recipients treated with high‐dose tacrolimus for 12 days. Group 1 animals (n = 3) received kidney and heart allografts fully MHC‐mismatched to each other and to the recipient. Group 2 animals (n = 3) received kidney and heart allografts MHC‐matched to each other but MHC‐mismatched to the recipient. Group 3 animals (n = 3) received chimeric kidney allografts whose parenchyma was MHC‐mismatched to the donor heart. Group 4 animals (n = 3) received chimeric kidney allografts whose passenger leukocytes were MHC‐mismatched to the donor heart. Five of six heart allografts in Groups 1 and 3 rejected <40 days. In contrast, heart allografts in Groups 2 and 4 survived >150 days without rejection (p < 0.05). These data demonstrate that KICAT requires MHC‐matching between kidney allograft parenchyma and heart allografts, suggesting that cells intrinsic to the kidney enable cardiac allograft tolerance.
Kidney‐induced cardiac allograft tolerance requires MHC‐matching between kidney allograft parenchyma and heart allografts, suggesting that cells intrinsic to the kidney enable cardiac allograft tolerance.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>25824550</pmid><doi>10.1111/ajt.13131</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Allografts Animals basic (laboratory) research / science Graft Rejection - immunology Graft Rejection - prevention & control Heart Heart - physiology Heart Transplantation heart transplantation / cardiology Histocompatibility - immunology Histocompatibility - physiology Immunosuppression Therapy Immunosuppressive Agents - therapeutic use Kidney - physiology Kidney Transplantation kidney transplantation / nephrology Major Histocompatibility Complex - immunology Major Histocompatibility Complex - physiology Models, Animal Swine Swine, Miniature Tacrolimus - therapeutic use Tissue and Organ Procurement tolerance tolerance: mechanisms Transplantation Tolerance - immunology Transplantation Tolerance - physiology |
| title | Kidney‐Induced Cardiac Allograft Tolerance in Miniature Swine is Dependent on MHC‐Matching of Donor Cardiac and Renal Parenchyma |
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