Modification of the rat alloimmune response by enhancing antibodies and the role of blocking factors in the survival of renal grafts

Abstract

Correlation of morphological and immunological events ocurring in control and passively enhanced rat renal allograft recipients has revealed an important role for vasculitis in rejection, whereas the tempo and severity of graft lymphocyte infiltration and tubular damage was comparable in both groups during the first 5 days. Thereafter, the degree of cellular infiltration in enhanced allografts progressed and actually exceeded that in control grafts. 2-Mercaptoethanol-sensitive lymphocytotoxic antibodies were present in both groups with comparable titers and appearance times; however, the presence of a severe IgG-containing necrotizing arteritis and glomerulitis in control, but not enhanced, grafts suggests that passive enhancement protects by interfereing with the cooperative T cell-dependent inductive response. Further support for this possibility comes from the fact that the development of cytotoxic lymphocytes against donor target cells was delayed for 48 hr in the enhanced group. While controls died at days 9-11, enhanced animals entered a period of prolonged survival with stable renal function. This state of "autoenhancement" was characterized by a low degree of cell-mediated cytotoxicity and the appearance of serum factors that blocked the in vitro cellular assay. Blocking factors have a low affinity for the attacking cell population, suggesting that they are immune complexes or anti-idiotypic antibodies, and not free alloantibody of high affinity.