Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo
We investigated the delivery of a donor-specific MHC class I gene, H-2Kb, using a newly constructed replication-defective recombinant adenovirus (AdSV40Kb) to recipient tissue before transplantation as a means of inducing donor-specific immunological unresponsiveness. AdSV40Kb was able to transduce...
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| Format: | Journal article |
| Language: | English |
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2002
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| _version_ | 1797097929663578112 |
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| author | Fry, J Morris, P Wood, K |
| author_facet | Fry, J Morris, P Wood, K |
| author_sort | Fry, J |
| collection | OXFORD |
| description | We investigated the delivery of a donor-specific MHC class I gene, H-2Kb, using a newly constructed replication-defective recombinant adenovirus (AdSV40Kb) to recipient tissue before transplantation as a means of inducing donor-specific immunological unresponsiveness. AdSV40Kb was able to transduce both a fibroblast cell line and freshly isolated bone marrow cells (BMCs) resulting in cell surface expression of H2-Kb protein. Intravenous infusion of AdSV40Kb-transduced syngeneic CBA/Ca (H-2k) BMCs into CBA recipient mice treated with an anti-CD4 monoclonal antibody 27 days before transplantation of a fully MHC-mismatched, C57BL/10 (H-2Kb+), cardiac allograft resulted in significant long-term graft survival when compared with mice receiving the same dose of syngeneic BMCs transduced with a control adenovirus, AdRSVβgal. Despite the induction of H-2Kb-specific hyporesponsiveness following pretreatment with AdSV40Kb-transduced CBA BMCs, persistence of H-2Kb mRNA in central or peripheral tissues could not be demonstrated by RT-PCR. This result was in contrast to the observed persistence of Kb mRNA both in the periphery and thymus following the infusion of transgenic CBK (H-2k + Kb) BMCs. We conclude that ex vivo adenoviral gene transfer of a single donor MHC class I gene to recipient BMCs in combination with transient depletion of CD4+ cells is sufficient to induce long-term graft survival of a fully allogeneic cardiac graft. In addition, detectable microchimerism is not a prerequisite for graft survival. |
| first_indexed | 2024-03-07T05:02:20Z |
| format | Journal article |
| id | oxford-uuid:d8b87dde-81b5-44a2-b452-3da804aa44df |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:02:20Z |
| publishDate | 2002 |
| record_format | dspace |
| spelling | oxford-uuid:d8b87dde-81b5-44a2-b452-3da804aa44df2022-03-27T08:50:44ZAdenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivoJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d8b87dde-81b5-44a2-b452-3da804aa44dfEnglishSymplectic Elements at Oxford2002Fry, JMorris, PWood, KWe investigated the delivery of a donor-specific MHC class I gene, H-2Kb, using a newly constructed replication-defective recombinant adenovirus (AdSV40Kb) to recipient tissue before transplantation as a means of inducing donor-specific immunological unresponsiveness. AdSV40Kb was able to transduce both a fibroblast cell line and freshly isolated bone marrow cells (BMCs) resulting in cell surface expression of H2-Kb protein. Intravenous infusion of AdSV40Kb-transduced syngeneic CBA/Ca (H-2k) BMCs into CBA recipient mice treated with an anti-CD4 monoclonal antibody 27 days before transplantation of a fully MHC-mismatched, C57BL/10 (H-2Kb+), cardiac allograft resulted in significant long-term graft survival when compared with mice receiving the same dose of syngeneic BMCs transduced with a control adenovirus, AdRSVβgal. Despite the induction of H-2Kb-specific hyporesponsiveness following pretreatment with AdSV40Kb-transduced CBA BMCs, persistence of H-2Kb mRNA in central or peripheral tissues could not be demonstrated by RT-PCR. This result was in contrast to the observed persistence of Kb mRNA both in the periphery and thymus following the infusion of transgenic CBK (H-2k + Kb) BMCs. We conclude that ex vivo adenoviral gene transfer of a single donor MHC class I gene to recipient BMCs in combination with transient depletion of CD4+ cells is sufficient to induce long-term graft survival of a fully allogeneic cardiac graft. In addition, detectable microchimerism is not a prerequisite for graft survival. |
| spellingShingle | Fry, J Morris, P Wood, K Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo |
| title | Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo |
| title_full | Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo |
| title_fullStr | Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo |
| title_full_unstemmed | Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo |
| title_short | Adenoviral transfer of a single donor-specific MHC class I gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo |
| title_sort | adenoviral transfer of a single donor specific mhc class i gene to recipient bone marrow cells can induce specific immunological unresponsiveness in vivo |
| work_keys_str_mv | AT fryj adenoviraltransferofasingledonorspecificmhcclassigenetorecipientbonemarrowcellscaninducespecificimmunologicalunresponsivenessinvivo AT morrisp adenoviraltransferofasingledonorspecificmhcclassigenetorecipientbonemarrowcellscaninducespecificimmunologicalunresponsivenessinvivo AT woodk adenoviraltransferofasingledonorspecificmhcclassigenetorecipientbonemarrowcellscaninducespecificimmunologicalunresponsivenessinvivo |