THE COURSE OF UNTREATED ACUTE REJECTION AND EFFECT OF REPEATED ANTI-CD3 MONOCLONAL ANTIBODY TREATMENT IN RHESUS MONKEY LIVER TRANSPLANTATION

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Abstract
The effect of single and repeated treatment of liver allograft rejection using an anti-CD3 monoclonal antibody (FN 18) 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 FN 18 (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 FN 18 but was successful in two animals with a low antimouse response. These four animals survived 1 GO-SOS 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.