Porcine endogenous retrovirus encodes xenoantigens involved in porcine cellular xenograft rejection by mice

Identification of the antigens that stimulate transplant rejection can help develop graft-specific antirejection strategies. The xenoantigens recognized during rejection of porcine cellular xenografts have not been clearly defined, but it has been assumed that major histocompatibility complex (MHC)...

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Veröffentlicht in:Transplantation 2005-06, Vol.79 (12), p.1674-1682
Hauptverfasser: SIMEONOVIC, Charmaine J, ZIOLKOWSKI, Andrew F, GIBBS, Adrian J, POPP, Sarah K, MILBURN, Peter J, LYNCH, Celina-Ann, HAMILTON, Peter, HARRIS, Karla, BROWN, Debra J, BAIN, Simon A. F, WILSON, J. Dennis
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container_end_page 1682
container_issue 12
container_start_page 1674
container_title Transplantation
container_volume 79
creator SIMEONOVIC, Charmaine J
ZIOLKOWSKI, Andrew F
GIBBS, Adrian J
POPP, Sarah K
MILBURN, Peter J
LYNCH, Celina-Ann
HAMILTON, Peter
HARRIS, Karla
BROWN, Debra J
BAIN, Simon A. F
WILSON, J. Dennis
description Identification of the antigens that stimulate transplant rejection can help develop graft-specific antirejection strategies. The xenoantigens recognized during rejection of porcine cellular xenografts have not been clearly defined, but it has been assumed that major histocompatibility complex (MHC) xenoantigens are involved. The role of porcine endogenous retrovirus (PERV) as a source of xenoantigens was examined. The authors used morphometry to compare the kinetics of swine leukocyte antigen (SLA) pig thyroid xenograft rejection in control mice and mice immunized with PERV PK15 cells (porcine kidney epithelial cells), PERV SLA pig peripheral blood lymphocytes (PBL), PERV virions purified from PK15 cells, and PERV or PERV A pseudotypes produced from infected human 293 cells. The tempo of rejection for cellular xenografts of PERV A pseudotype-producing human 293 cells, uninfected human 293 cells, and PK15 cells in PERV-preimmunized and control mice was also compared. Mice immunized with PK15 cells rejected pig thyroid xenografts significantly faster at day 5 than control mice and mice immunized with pig PBL. This correlated with the amount of PERV RNA and virions produced, but not with the amount of SLA class I MHC expressed by PK15 cells. Immunization of mice with PERV virions purified from porcine PK15 cells and with PERV virions or PERV A pseudotypes produced by human 293 cells also induced accelerated xenograft rejection by 5 days. Accelerated rejection induced by virus pretreatment was CD4 T-cell dependent and restricted to PERV-expressing cellular xenografts of porcine or nonporcine origin. PERV acts as a significant source of xenoantigens that target porcine cellular xenografts for rejection.
doi_str_mv 10.1097/01.TP.0000164316.55216.07
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The authors used morphometry to compare the kinetics of swine leukocyte antigen (SLA) pig thyroid xenograft rejection in control mice and mice immunized with PERV PK15 cells (porcine kidney epithelial cells), PERV SLA pig peripheral blood lymphocytes (PBL), PERV virions purified from PK15 cells, and PERV or PERV A pseudotypes produced from infected human 293 cells. The tempo of rejection for cellular xenografts of PERV A pseudotype-producing human 293 cells, uninfected human 293 cells, and PK15 cells in PERV-preimmunized and control mice was also compared. Mice immunized with PK15 cells rejected pig thyroid xenografts significantly faster at day 5 than control mice and mice immunized with pig PBL. This correlated with the amount of PERV RNA and virions produced, but not with the amount of SLA class I MHC expressed by PK15 cells. 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F</creatorcontrib><creatorcontrib>WILSON, J. Dennis</creatorcontrib><title>Porcine endogenous retrovirus encodes xenoantigens involved in porcine cellular xenograft rejection by mice</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Identification of the antigens that stimulate transplant rejection can help develop graft-specific antirejection strategies. The xenoantigens recognized during rejection of porcine cellular xenografts have not been clearly defined, but it has been assumed that major histocompatibility complex (MHC) xenoantigens are involved. The role of porcine endogenous retrovirus (PERV) as a source of xenoantigens was examined. 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Graft diseases</subject><subject>Swine</subject><subject>Swine, Miniature</subject><subject>Thyroid Gland - transplantation</subject><subject>Tissue, organ and graft immunology</subject><subject>Transplantation, Heterologous - pathology</subject><subject>Virion - genetics</subject><subject>Virion - isolation &amp; purification</subject><issn>0041-1337</issn><issn>1534-6080</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9PGzEQxS0EKoH2K6DlQG8b_N-7R4Roi4REDunZ8tpjZLqxU3sTwbfHwEo54oM9kn_vzYweQpcELwnu1TUmy_VqieshkjMil0LQemN1hBZEMN5K3OFjtMCYk5Ywpk7RWSnPlRdMqW_olIheVV23QP9WKdsQoYHo0hPEtCtNhimnfci1hGiTg9K81B8Tp1CJ0oS4T-MeXC2a7Sy3MI670eQP8ikbP1WbZ7BTSLEZXptNsPAdnXgzFvgxv-fo76-79e2f9uHx9_3tzUNrOVVTC90APQyUK-qd5KZTzlnGe2uUqYtSb5XxzlIuqOXK28EpJ5nHQoBTHbHsHP389N3m9H8HZdKbUN4HNBHqflqqXlJB6JcgUYIJyfoK9p-gzamUDF5vc9iY_KoJ1u-RaEz0eqUPkeiPSDRWVXsxN9kNG3AH5ZxBBa5mwBRrRp9NtKEcONlzIaVkbxG7l_s</recordid><startdate>20050627</startdate><enddate>20050627</enddate><creator>SIMEONOVIC, Charmaine J</creator><creator>ZIOLKOWSKI, Andrew F</creator><creator>GIBBS, Adrian J</creator><creator>POPP, Sarah K</creator><creator>MILBURN, Peter J</creator><creator>LYNCH, Celina-Ann</creator><creator>HAMILTON, Peter</creator><creator>HARRIS, Karla</creator><creator>BROWN, Debra J</creator><creator>BAIN, Simon A. 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Graft diseases</topic><topic>Swine</topic><topic>Swine, Miniature</topic><topic>Thyroid Gland - transplantation</topic><topic>Tissue, organ and graft immunology</topic><topic>Transplantation, Heterologous - pathology</topic><topic>Virion - genetics</topic><topic>Virion - isolation &amp; purification</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SIMEONOVIC, Charmaine J</creatorcontrib><creatorcontrib>ZIOLKOWSKI, Andrew F</creatorcontrib><creatorcontrib>GIBBS, Adrian J</creatorcontrib><creatorcontrib>POPP, Sarah K</creatorcontrib><creatorcontrib>MILBURN, Peter J</creatorcontrib><creatorcontrib>LYNCH, Celina-Ann</creatorcontrib><creatorcontrib>HAMILTON, Peter</creatorcontrib><creatorcontrib>HARRIS, Karla</creatorcontrib><creatorcontrib>BROWN, Debra J</creatorcontrib><creatorcontrib>BAIN, Simon A. F</creatorcontrib><creatorcontrib>WILSON, J. 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Dennis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Porcine endogenous retrovirus encodes xenoantigens involved in porcine cellular xenograft rejection by mice</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2005-06-27</date><risdate>2005</risdate><volume>79</volume><issue>12</issue><spage>1674</spage><epage>1682</epage><pages>1674-1682</pages><issn>0041-1337</issn><eissn>1534-6080</eissn><coden>TRPLAU</coden><abstract>Identification of the antigens that stimulate transplant rejection can help develop graft-specific antirejection strategies. The xenoantigens recognized during rejection of porcine cellular xenografts have not been clearly defined, but it has been assumed that major histocompatibility complex (MHC) xenoantigens are involved. The role of porcine endogenous retrovirus (PERV) as a source of xenoantigens was examined. The authors used morphometry to compare the kinetics of swine leukocyte antigen (SLA) pig thyroid xenograft rejection in control mice and mice immunized with PERV PK15 cells (porcine kidney epithelial cells), PERV SLA pig peripheral blood lymphocytes (PBL), PERV virions purified from PK15 cells, and PERV or PERV A pseudotypes produced from infected human 293 cells. The tempo of rejection for cellular xenografts of PERV A pseudotype-producing human 293 cells, uninfected human 293 cells, and PK15 cells in PERV-preimmunized and control mice was also compared. Mice immunized with PK15 cells rejected pig thyroid xenografts significantly faster at day 5 than control mice and mice immunized with pig PBL. This correlated with the amount of PERV RNA and virions produced, but not with the amount of SLA class I MHC expressed by PK15 cells. Immunization of mice with PERV virions purified from porcine PK15 cells and with PERV virions or PERV A pseudotypes produced by human 293 cells also induced accelerated xenograft rejection by 5 days. Accelerated rejection induced by virus pretreatment was CD4 T-cell dependent and restricted to PERV-expressing cellular xenografts of porcine or nonporcine origin. PERV acts as a significant source of xenoantigens that target porcine cellular xenografts for rejection.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>15973168</pmid><doi>10.1097/01.TP.0000164316.55216.07</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Antigens, Heterophile - immunology
Antigens, Viral - immunology
Base Sequence
Biological and medical sciences
Cell Line
DNA Primers
Endogenous Retroviruses - genetics
Endogenous Retroviruses - isolation & purification
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Graft Rejection - pathology
Graft Rejection - virology
Humans
Major Histocompatibility Complex
Male
Medical sciences
Mice
Mice, Inbred CBA
Mice, SCID
Porcine endogenous retrovirus
Reverse Transcriptase Polymerase Chain Reaction
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Swine
Swine, Miniature
Thyroid Gland - transplantation
Tissue, organ and graft immunology
Transplantation, Heterologous - pathology
Virion - genetics
Virion - isolation & purification
title Porcine endogenous retrovirus encodes xenoantigens involved in porcine cellular xenograft rejection by mice
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