Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats
Interleukin-10 (IL-10) and interleukin-4 (IL-4), two Th2-derived cytokines, are molecules with anti-inflammatory and immunodeviating properties whose direct expression in allografts may prolong graft survival. Recombinant adenoviruses represent efficient vectors for gene transfer in quiescent cells...
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| Veröffentlicht in: | Gene therapy 2000-03, Vol.7 (6), p.505-510 |
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| creator | DAVID, A CHETRITT, J GUILLOT, C TESSON, L HESLAN, J.-M CUTURI, M.-C SOULILLOU, J.-P ANEGON, I |
| description | Interleukin-10 (IL-10) and interleukin-4 (IL-4), two Th2-derived cytokines, are molecules with anti-inflammatory and immunodeviating properties whose direct expression in allografts may prolong graft survival. Recombinant adenoviruses represent efficient vectors for gene transfer in quiescent cells in vivo. Adenoviral vectors encoding rat IL-10 (AdIL-10), rat IL-4 (AdIL-4) or beta-galactosidase (AdlacZ) or without transgene (Addl324) were injected directly into rat hearts at the time of transplantation in order to test their potential to prolong heart allograft survival. Expression of vectorized sequences was confirmed in heart biopsies, and kinetic analysis of beta-galactosidase showed transient expression. Cardiac allograft survival was significantly prolonged after administration of 10(9) p.f.u. of AdIL-10 (16.6 +/- 3.2 days, P < 0.05), but not AdIL-4 (9.8 +/- 1.6 days), compared with Addl324-treated (9.3 +/- 3.3 days) or untreated groups (7.8 +/- 1.5 days). Immunohistochemical analysis of allografts after gene transfer of IL-10 showed that leukocyte infiltration was quantitatively equivalent to that seen in control groups but with a strong tendency towards lower levels of CD8+ cells. Importantly, adenovirus-derived IL-10 modified the functional status of leukocytes by inducing a significant decrease in IFN-gamma production but significantly increased transforming-growth factor beta 1 (TGF-beta 1) expression within the grafts compared with those treated with Addl324. These results show that expression of IL-10 by rat hearts after gene transfer mediated by an adenoviral vector decreases allogeneic immune responses and allows prolongation of allograft survival. |
| doi_str_mv | 10.1038/sj.gt.3301114 |
| format | Article |
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Recombinant adenoviruses represent efficient vectors for gene transfer in quiescent cells in vivo. Adenoviral vectors encoding rat IL-10 (AdIL-10), rat IL-4 (AdIL-4) or beta-galactosidase (AdlacZ) or without transgene (Addl324) were injected directly into rat hearts at the time of transplantation in order to test their potential to prolong heart allograft survival. Expression of vectorized sequences was confirmed in heart biopsies, and kinetic analysis of beta-galactosidase showed transient expression. Cardiac allograft survival was significantly prolonged after administration of 10(9) p.f.u. of AdIL-10 (16.6 +/- 3.2 days, P < 0.05), but not AdIL-4 (9.8 +/- 1.6 days), compared with Addl324-treated (9.3 +/- 3.3 days) or untreated groups (7.8 +/- 1.5 days). Immunohistochemical analysis of allografts after gene transfer of IL-10 showed that leukocyte infiltration was quantitatively equivalent to that seen in control groups but with a strong tendency towards lower levels of CD8+ cells. Importantly, adenovirus-derived IL-10 modified the functional status of leukocytes by inducing a significant decrease in IFN-gamma production but significantly increased transforming-growth factor beta 1 (TGF-beta 1) expression within the grafts compared with those treated with Addl324. These results show that expression of IL-10 by rat hearts after gene transfer mediated by an adenoviral vector decreases allogeneic immune responses and allows prolongation of allograft survival.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/sj.gt.3301114</identifier><identifier>PMID: 10757024</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Adenoviridae - genetics ; Adenovirus ; Adenoviruses ; Allografts ; Animals ; beta-Galactosidase - genetics ; Biological and medical sciences ; Biopsy ; Biotechnology ; CD8 antigen ; Cytokines ; Expression vectors ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene therapy ; Gene transfer ; Gene Transfer Techniques ; Genetic Therapy - methods ; Genetic Vectors - administration & dosage ; Graft Rejection - immunology ; Graft Rejection - prevention & control ; Health. Pharmaceutical industry ; Heart transplantation ; Heart Transplantation - immunology ; Immune response ; Immunohistochemistry ; Immunotherapy - methods ; Industrial applications and implications. Economical aspects ; Inflammation ; Interleukin 10 ; Interleukin 4 ; Interleukin-10 - genetics ; Interleukin-10 - therapeutic use ; Interleukin-4 - genetics ; Leukocytes ; Lymphocytes T ; Rats ; Transforming growth factor-b1 ; Transplantation, Homologous ; β-Galactosidase ; γ-Interferon</subject><ispartof>Gene therapy, 2000-03, Vol.7 (6), p.505-510</ispartof><rights>2000 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Mar 2000</rights><rights>Macmillan Publishers Limited 2000.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c443t-290ac0125a20f33ba1213f6e7e4af32e90f69d6227e03b851f57c35ef318ad3f3</citedby><cites>FETCH-LOGICAL-c443t-290ac0125a20f33ba1213f6e7e4af32e90f69d6227e03b851f57c35ef318ad3f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27928,27929</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1304726$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10757024$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DAVID, A</creatorcontrib><creatorcontrib>CHETRITT, J</creatorcontrib><creatorcontrib>GUILLOT, C</creatorcontrib><creatorcontrib>TESSON, L</creatorcontrib><creatorcontrib>HESLAN, J.-M</creatorcontrib><creatorcontrib>CUTURI, M.-C</creatorcontrib><creatorcontrib>SOULILLOU, J.-P</creatorcontrib><creatorcontrib>ANEGON, I</creatorcontrib><title>Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><description>Interleukin-10 (IL-10) and interleukin-4 (IL-4), two Th2-derived cytokines, are molecules with anti-inflammatory and immunodeviating properties whose direct expression in allografts may prolong graft survival. Recombinant adenoviruses represent efficient vectors for gene transfer in quiescent cells in vivo. Adenoviral vectors encoding rat IL-10 (AdIL-10), rat IL-4 (AdIL-4) or beta-galactosidase (AdlacZ) or without transgene (Addl324) were injected directly into rat hearts at the time of transplantation in order to test their potential to prolong heart allograft survival. Expression of vectorized sequences was confirmed in heart biopsies, and kinetic analysis of beta-galactosidase showed transient expression. Cardiac allograft survival was significantly prolonged after administration of 10(9) p.f.u. of AdIL-10 (16.6 +/- 3.2 days, P < 0.05), but not AdIL-4 (9.8 +/- 1.6 days), compared with Addl324-treated (9.3 +/- 3.3 days) or untreated groups (7.8 +/- 1.5 days). Immunohistochemical analysis of allografts after gene transfer of IL-10 showed that leukocyte infiltration was quantitatively equivalent to that seen in control groups but with a strong tendency towards lower levels of CD8+ cells. Importantly, adenovirus-derived IL-10 modified the functional status of leukocytes by inducing a significant decrease in IFN-gamma production but significantly increased transforming-growth factor beta 1 (TGF-beta 1) expression within the grafts compared with those treated with Addl324. These results show that expression of IL-10 by rat hearts after gene transfer mediated by an adenoviral vector decreases allogeneic immune responses and allows prolongation of allograft survival.</description><subject>Adenoviridae - genetics</subject><subject>Adenovirus</subject><subject>Adenoviruses</subject><subject>Allografts</subject><subject>Animals</subject><subject>beta-Galactosidase - genetics</subject><subject>Biological and medical sciences</subject><subject>Biopsy</subject><subject>Biotechnology</subject><subject>CD8 antigen</subject><subject>Cytokines</subject><subject>Expression vectors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene therapy</subject><subject>Gene transfer</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>Genetic Vectors - administration & dosage</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - prevention & control</subject><subject>Health. Pharmaceutical industry</subject><subject>Heart transplantation</subject><subject>Heart Transplantation - immunology</subject><subject>Immune response</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy - methods</subject><subject>Industrial applications and implications. 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Recombinant adenoviruses represent efficient vectors for gene transfer in quiescent cells in vivo. Adenoviral vectors encoding rat IL-10 (AdIL-10), rat IL-4 (AdIL-4) or beta-galactosidase (AdlacZ) or without transgene (Addl324) were injected directly into rat hearts at the time of transplantation in order to test their potential to prolong heart allograft survival. Expression of vectorized sequences was confirmed in heart biopsies, and kinetic analysis of beta-galactosidase showed transient expression. Cardiac allograft survival was significantly prolonged after administration of 10(9) p.f.u. of AdIL-10 (16.6 +/- 3.2 days, P < 0.05), but not AdIL-4 (9.8 +/- 1.6 days), compared with Addl324-treated (9.3 +/- 3.3 days) or untreated groups (7.8 +/- 1.5 days). Immunohistochemical analysis of allografts after gene transfer of IL-10 showed that leukocyte infiltration was quantitatively equivalent to that seen in control groups but with a strong tendency towards lower levels of CD8+ cells. Importantly, adenovirus-derived IL-10 modified the functional status of leukocytes by inducing a significant decrease in IFN-gamma production but significantly increased transforming-growth factor beta 1 (TGF-beta 1) expression within the grafts compared with those treated with Addl324. These results show that expression of IL-10 by rat hearts after gene transfer mediated by an adenoviral vector decreases allogeneic immune responses and allows prolongation of allograft survival.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>10757024</pmid><doi>10.1038/sj.gt.3301114</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Gene therapy, 2000-03, Vol.7 (6), p.505-510 |
| issn | 0969-7128 1476-5462 |
| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Adenoviridae - genetics Adenovirus Adenoviruses Allografts Animals beta-Galactosidase - genetics Biological and medical sciences Biopsy Biotechnology CD8 antigen Cytokines Expression vectors Fundamental and applied biological sciences. Psychology Gene Expression Gene therapy Gene transfer Gene Transfer Techniques Genetic Therapy - methods Genetic Vectors - administration & dosage Graft Rejection - immunology Graft Rejection - prevention & control Health. Pharmaceutical industry Heart transplantation Heart Transplantation - immunology Immune response Immunohistochemistry Immunotherapy - methods Industrial applications and implications. Economical aspects Inflammation Interleukin 10 Interleukin 4 Interleukin-10 - genetics Interleukin-10 - therapeutic use Interleukin-4 - genetics Leukocytes Lymphocytes T Rats Transforming growth factor-b1 Transplantation, Homologous β-Galactosidase γ-Interferon |
| title | Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats |
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