ASSESSMENT OF TOLERANCE INDUCTION TO CARDIAC ALLOGRAFT BY ANTI-ICAM-1AND ANTI-LFA-1 MONOCLONAL-ANTIBODIES

Background: Transplantation tolerance is induced by selective manipula tion of intercellular adhesion molecule-1 (ICAM-1) and leukocyte funct ion-associated antigen-1 (LFA-1) molecules in the adult mouse. However , the mechanism of this tolerance induction has not been elucidated. M ethods and Results: C3H/He mice were heterotopically transplanted with BALB/c hearts; recipients were injected with anti-ICAM-1 and anti-LFA -l monoclonal antibodies (mAbs). Of 3-day administration of both mAbs at 50 mu g/day, all recipients accepted cardiac allografts indefinitel y (n = 20); this also occurred in 5 of 10 mice that were not treated u ntil day +4 or day +5. Long-term cardiac allograft acceptance was also achieved in thymectomized recipients. This tolerance could not be abr ogated by the injection of either naive recipient lymphocytes or sensi tized lymphocytes taken from the recipient strain mice that rejected t he same donor strain hearts. Mixed lymphocyte culture showed that sple nocytes from allograft recipient mice treated with the mAbs showed nor mal allogeneic response without donor alloantigen specificity. Conclus ions: These results demonstrate the unique character of the peripheral tolerance induced by anti-ICAM-1 and anti-LFA-l mAbs. Further studies are required to elucidate detailed mechanisms of transplantation tole rance development. J Heart Lung Transplant 1997.