Background: Liver transplants may be less susceptible to rejection and may protect other transplanted organs from rejection, because the liver produces large amounts of soluble MHC class I antigen. Most studies supporting this hypothesis have used in vitro models. Here we tested the application of this theory in vivo in a rat transplant model.
Methods: Primary cultured Lewis (RT1.A(l)) hepatocytes were transfected by lipofection with plasmids encoding allogeneic membrane-bound or secreted RT1.A(a). After portal vein injection of transfected hepatocytes into a Lewis rat, either an ACI (RT1.A(a)) liver transplant was performed or lymph nodes were removed for immunologic analysis.
Results: Rats injected with hepatocytes secreting alloantigen showed extended liver allograft survival and decreased cytotoxic T lymphocyte activity. Recipients injected with hepatocytes expressing membrane-bound alloantigen demonstrated accelerated graft rejection and showed cytotoxic T lymphocyte sensitization.
Conclusions: Soluble donor-specific MHC class I molecules may have immunosuppressive effects that can be used to promote graft survival in an organ transplantation situation.