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  • Gene transfer  (1)
  • Key words MHC  (1)
  • MHC antigen  (1)
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  • 1
    ISSN: 1432-2277
    Keywords: Key words MHC ; Hepatocyte ; CTL ; Gene transfer ; Liver
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies suggest liver transplants can protect other transplanted organs. This effect may be mediated by hepatocytes secreting large amounts of soluble MHC class I antigen. Here our aim was to determine whether immunologic priming by membrane-bound alloantigen could be inhibited by allospecific antigen produced in a secreted form. Cultured Lewis (RT1.Al) hepatocytes were transfected with plasmids encoding either a membrane-bound or secreted form of the alloantigen, RT1.Aa. Cytotoxic T-lymphocyte (CTL) precursor assays were performed on Lewis splenocytes cultured with transfected hepatocytes, or hepatocytes were injected into the portal vein of prospective Lewis recipients of an ACI (RT1.Aa) liver allograft. Results showed CTL priming by membrane-bound RT1.Aa was inhibited in vitro by soluble RT1.Aa. Similarly, acceleration of ACI allograft rejection induced by membrane-bound antigen was abrogated following co-injection of hepatocytes secreting donor alloantigen. In conclusion, production of soluble donor alloantigen by liver transplants may provide protection against the alloimmune response.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2277
    Keywords: Key words Thymus ; MHC antigen ; Heart transplantation ; Immunosuppression ; Gene therapy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Thymic selection of self and non-self-reactive lymphocytes is a process that may be targeted to induce donor-specific immunologic unresponsiveness in organ transplantation. In the present study, gene transfer was used to preexpose the recipient thymus to soluble donor-specific MHC class I molecules prior to heart transplantation in the high-responder ACI (RT1a) to Lewis (RT1l) rat strain combination. Specifically, cultured Lewis hepatocytes were transfected with DNA encoding a secreted form of the donor allo-MHC class I antigen, RT1.Aa. Seven days prior to ACI heart transplantation, genetically altered recipient-strain hepatocytes were injected into the thymus of Lewis recipients which also received a dose of antilymphocyte serum (ALS). Results showed that treatment with both ALS and soluble donor MHC-expressing hepatocytes prolonged transplant survival time by twofold, compared to injection of control hepatocytes and ALS. Therefore, intrathymic gene therapy delivery of soluble donor MHC molecules may be useful for promoting allograft survival in heart transplantation.
    Type of Medium: Electronic Resource
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