Murine liver allograft transplantation: tolerance and donor cell chimerism.
Nonarterialized orthotopic liver transplantation with no immunosuppression was performed in 13 mouse-strain combinations. Two strain combinations with major histocompatibility complex class I and class II and minor histocompatibility complex disparity had 20% and 33% survival of more than 100 days, but the other 11 combinations, including four that were fully allogeneic and all with only class I, class II or minor disparities, yielded 45% to 100% survival of more than 100 days. Long-living recipients permanently accepted donor-strain heterotopic hearts transplanted on the same day or donor-strain skin 3 mo after liver transplantation, in spite of detectable antidonor in vitro activity with mixed lymphocyte reaction and cell-mediated lymphocytotoxicity testing (split tolerance). In further donor-specific experiments, liver grafts were not rejected by presensitized major histocompatibility complex class I-disparate recipients and they protected donor-strain skin grafts from second set (or any) rejection. Less frequently, liver transplantation rescued rejecting skin grafts placed 1 wk earlier in major histocompatibility complex class I, class II and minor histocompatibility complex, class II or minor histocompatibility complex-disparate strain combinations. Donor-derived leukocyte migration to the central lymphoid organs occurred within 1 to 2 hr after liver transplantation in all animals examined, persisted in the surviving animals until they were killed (> 375 days), and was demonstrated with double-immunolabeling to be multilineage. The relation of these findings to so-called hepatic tolerogenicity and to tolerance in general is discussed.
Qian
S
S
Pittsburgh Transplant Institute, University of Pittsburgh Medical Center, Pennsylvania 15213.
Demetris
A J
AJ
Murase
N
N
Rao
A S
AS
Fung
J J
JJ
Starzl
T E
TE
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D016031:Liver Transplantation / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D016038:Skin Transplantation / Q000276:immunology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II