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Post‐transplant upr...
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Hårdstedt, Maria,1971-Uppsala universitet,Klinisk immunologi,Korsgren
(author)
Post‐transplant upregulation of chemokine messenger RNA in non‐human primate recipients of intraportal pig islet xenografts
- Article/chapterEnglish2005
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John Wiley & Sons,2005
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Numbers
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LIBRIS-ID:oai:DiVA.org:oru-111597
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https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-111597URI
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https://doi.org/10.1111/j.1399-3089.2005.00228.xDOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-233185URI
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
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BACKGROUND: We have previously shown that pig-to-primate intraportal islet xenografts reverse diabetes, escape hyperacute rejection, and undergo acute cellular rejection in non-immunosuppressed recipients. To gain a better understanding of mechanisms contributing to xenoislet rejection in non-human primates we examined gene expression in livers bearing islet xenografts in the first 72 h after transplantation.METHODS: Liver specimens were collected at sacrifice from seven non-immunosuppressed rhesus macaques at 12, 24, 48 and 72 h after intraportal porcine islet transplantation. Following total RNA extraction, mRNA was quantified using SYBR green real-time reverse transcription polymerase chain reaction (RT-PCR) for species-specific immune response genes. Data were analyzed using comparative cycle threshold (Ct) analysis, adjusted for specific primer-efficiencies and normalized to cyclophilin expression.RESULTS: Porcine insulin mRNA was detected in all liver samples. Cluster analysis revealed differential gene expression patterns at 12 and 24 h (early) compared with at 48 and 72 h (late) post-transplant. Gene expression patterns were associated with histological findings of predominantly neutrophils and only a few lymphocytes at 12 and 24 h and an increasing number of lymphocytes and macrophages at 48 and 72 h. Transcript levels of CXCR3 and its ligands, interferon-inducible protein 10 (IP-10) and monokine induced by IFN-gamma (Mig), significantly increased between early and late time points together with expression of MIP-1alpha, regulated on activation normal T expressed and secreted protein (RANTES) and MCP-1. CCR5 showed only a marginal, non-significant increase. Fas ligand, perforin and granzyme B transcripts were all elevated at 48 and 72 h post-transplant.CONCLUSIONS: Our data suggest that CXCR3, with ligands IP-10 and Mig, is involved in T cell recruitment in acute islet xenograft rejection in non-human primates. Upregulation of RANTES and MIP-1alpha transcripts in the absence of a significant CCR5 increase suggests a possible involvement of other chemokine receptors. MCP-1 expression is associated with T cell and macrophage infiltration. Elevated cytotoxic effector molecule expression (Fas ligand, perforin, granzyme B) indicates T-cell mediated graft destruction by cytotoxic and cytolytic mechanisms within 48 to 72 h after transplantation. These results identify the CXCR3-mediated chemoattractant pathway as an immunosuppressive target in pig-to-primate islet xenotransplantation.
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Finnegan, Colleen P.Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, MN, USA
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Kirchhof, NicoleDiabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis MN, USA
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Hyland, Kendra A.Departmentof Veterinary and Biomedical Sciences, University ofMinnesota, St Paul, MN, USA
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Wijkstrom, MartinDiabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis MN, USA
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Murtaugh, Michael P.Department of Veterinary and Biomedical Sciences, University of Minnesota, St Paul, MN, USA
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Hering, Bernhard J.Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis MN, USA
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Uppsala universitetKlinisk immunologi
(creator_code:org_t)
Related titles
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In:Xenotransplantation: John Wiley & Sons12:4, s. 293-3020908-665X1399-3089
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