Soluble donor MHC class I antigen inhibits immunologic priming in vitro and in vivo

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.A1) 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.