Secreted donor-MHC class I antigen prolongs liver allograft survival and inhibits recipient anti-donor cytotoxic T lymphocyte responses.
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.
Geissler
E K
EK
Department of Medical Technology, University of South Alabama, Mobile 36604-3273, USA.
Korzun
W J
WJ
Graeb
C
C
D000818:Animals; D006085:Graft Survival / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D008099:Liver / Q000166:cytology*; D016031:Liver Transplantation / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000502:physiology*; D014162:Transfection
D015395:Histocompatibility Antigens Class I