Potent and effective prolongation by anti-LFA-1 monoclonal antibody monotherapy of non-primarily vascularized heart allograft survival in mice without T cell depletion

Monoclonal antibodies (MAbs) against lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18) led to the initial identification and investigation of the function of these leukocyte cell-surface glycoproteins. LFA-1 and its ligands, ICAM-1 and -2, are adhesion molecules responsible for specific interactions between immune cells and nonimmune cells. A recent report showed brief treatment with either anti-LFA-1 or anti-ICAM-1 MAbs minimally prolonged the survival of primarily vascularized heterotopic heart allografts in mice; combined treatment with both MAbs was required, however, to achieve long-term graft survival in this model. Independently, we showed that treatment with anti-LFA-1 MAb alone potently and effectively prolongs the survival of heterotopic (ear-pinna) nonprimarily vascularized mouse heart grafts. Nonprimarily vascularized heart allografts are more immunogenic and more resistant to prolongation of survival by MAbs than primarily vascularized heart allografts. This article describes our initial findings in detail. We also show that indefinite graft survival in anti-LFA-1 MAb-treated mice cannot be explained by the induction of persistent, nonspecific immunosuppression.