Treatment with monoclonal antibodies to ICAM-1 and LFA-1 in rat heart allograft rejection

Abstract

During allograft rejection, leukocyte infiltration in the graft is regulated by various adhesion molecules. Treatment with monoclonal antibodies to ICAM-1 and LFA-1 (CD11 a) induces specific tolerance after murine heart transplantation. In this study, we investigated the possibility of tolerance induction using these antibodies in a fully incompatible rat heart transplant model. Heterotopic, intra-abdominal heart transplantation was performed using Dark Agouti (DA) rats as donors and Lewis (LEW) rats as recipients. Group A (n = 6) received no immunosuppression and served as controls. In group B (n = 6) 500 μg/kg per day 1A29 (anti-ICAM-1) was administered intravenously (i. v.) for 5 days; group C rats received the same dosage of WT.1 (anti-CD11 a) i. v. for 5 days. In group D (n = 6), rats received combined i. v. administration of anti-CD11 a and anti-ICAM-1 (500 μg/kg per day of each, for 5 days. The antibodies used were monoclonal mouse anti-rat antibodies produced from hybridomas. Allograft survival was monitored by daily palpation of the graft. There was no statistically significant difference in allograft survival between the groups (A: 5.7 ± 0.5 days; B: 5.7 ± 0.5 days; C: 5.7 ± 0.5 days; D: 6.2 ± 0.4 days). Treatment with monoclonal antibodies to ICAM-1 and LFA-1 alone or in combination had no effect on allograft survival after heart transplantation between fully incompatible rat strains. We conclude that induction of tolerance using these antibodies seems inconceivable in human heart transplantation.