CARDIAC ALLOGRAFT VASCULOPATHY IS ABROGATED ANTI-CD8 MONOCLONAL-ANTIBODY THERAPY

Background. Cardiac allograft vasculopathy, a diffuse and accelerated form of arteriosclerosis, is a major cause of graft loss or heart tran splant recipient death after the first transplant year. This study exa mined the effects of depleting host CD8+ T lymphocytes on the developm ent of cardiac allograft vasculopathy in miniature swine. Methods. Car diac allografts were heterotopically transplanted across a major histo compatibility complex class I barrier in partially inbred miniature sw ine and monitored for rejection by serial biopsies, electrocardiograms , and echocardiograms. Four control animals received cyclosporine on p ostoperative days 0 to 11. Another four miniswine were given 14.5 mg/k g of 76-2-11 (a mouse anti-swine CD8 monoclonal antibody) on postopera tive day 0, in addition to a 12-day course of cyclosporine. Host CD8T cells and circulating 76-2-11 monoclonal antibodies were monitored b y now cytometry. Results. As compared with cyclosporine-treated contro l animals, swine receiving 76-2-11 demonstrated near-complete depletio n of peripheral CD8+ T cells by postoperative day 2, which persisted f or 14 to 18 days. Mean allograft survival of the antibody-treated grou p and the control group was not statistically different (33 days versu s 39 days, respectively) and both groups demonstrated severe interstit ial rejection at necropsy. Control animals demonstrated florid intimal thickening of large and small arteries at necropsy. However, swine tr eated with 76-2-11 showed no intimal proliferation. Conclusions. Deple tion of host CD8+ T cells prevents or delays the development of intima l proliferation in miniature swine. CD8+ lymphocytes play an important role in the early development of cardiac allograft vasculopathy in la rge animals. (C) 1997 by The Society of Thoracic Surgeons.