The course of untreated acute rejection and effect of repeated anti-CD3 monoclonal antibody treatment in rhesus monkey liver transplantation.
The effect of single and repeated treatment of liver allograft rejection using an anti-CD3 monoclonal antibody (FN18) was studied in a rhesus monkey model. Eight RhLA-mismatched monkeys received initial postoperative immunosuppression with CsA/prednisolone for 28 days. After cessation, acute rejection occurred in all animals (days 28-50). Control animals (n = 3) receiving no rejection treatment developed a chronic progressive rejection and died at days 112-160. In the animals treated with FN18 (n = 5), the first acute rejection was successfully reversed. T lymphocytes were cleared from the peripheral blood and the graft. Increased class I and class II MHC-antigens on hepatocytes were reduced to normal levels within 5 days of treatment. The second rejection treatment remained ineffective in two animals with antiidiotypic antibodies to FN18 but was successful in two animals with a low antimouse response. These four animals survived 160-509 days. The results have a number of implications regarding the course of untreated rejection in human liver transplant recipients and repetitive rejection treatment with monoclonal antibodies.
Steinhoff
G
G
Klinik für Abdominal-und Transplantationschirurgie, Medizinische Hochschule Hannover, Federal Republic of Germany.
Jonker
M
M
Gubernatis
G
G
Wonigeit
K
K
Lauchart
W
W
Bornscheuer
A
A
Pichlmayr
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017252:CD3 Complex / Q000276:immunology*; D003524:Cyclosporins / Q000494:pharmacology; D006084:Graft Rejection / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000032:analysis; D007958:Leukocyte Count; D016031:Liver Transplantation / Q000276:immunology*; D008253:Macaca mulatta; D011239:Prednisolone / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D003524:Cyclosporins; D006649:Histocompatibility Antigens; D011239:Prednisolone