CORONARY ATHEROSCLEROSIS IN TRANSPLANTED MOUSE HEARTS .2. IMPORTANCE OF HUMORAL IMMUNITY

Obstructive lesions in arterial vessels of transplanted organs constit ute an important factor in the late failure of these organs, especiall y for the heart. The absence of obstructive lesions in syngeneic donor -recipient combinations, suggests that they depend upon recipient immu ne responsiveness. It is controversial whether humoral or cellular asp ects of the immune response predominate in the process. The present ex periments employed hearts transplanted between inbred mice. After brie f preoperative immunosuppression of recipients with mAbs to CD4 and CD 8 determinants, hearts transplanted between mice incompatible for hist ocompatibility Ags survived for prolonged periods and most developed t ypical, obstructive coronary lesions. Our quantitative scoring of vasc ular changes on tissue sections of excised hearts, grades both their s everity and prevalence. Transplants between strains that produced Abs to donor cells (B10.A to B10.BR), developed coronary lesions exceeding those in the reverse combination in which no detectable Ab was formed (B10.BR to B10.A; p < 0.00001), even though their histoincompatibilit y was similar. Treatment of B10.A recipients of B10.BR hearts with an antiserum against the donor significantly increased coronary lesions ( p < 0.0003) in a dose-dependent fashion. Coronary arteries of B10.BR h earts transplanted to C.B-17 SCID mice remained largely free of lesion s, whereas transplants to SCID recipients that received continuing inj ections of an antiserum directed to Ags of the donor developed strikin g, obstructive coronary lesions. We conclude that humoral immunity can be the prime instigator of atheromatous changes that occur in transpl anted hearts.