Analysis of Mechanisms of Maintenance of Neonatally Induced Tolerance to Foreign Alloantigens

Abstract

Mice made tolerant to allogeneic tissues in neonatal life have been examined at different times for their ability to respond to the tolerizing determinants in a variety of assays (in vitro CML, MCL and in vivo GvH assays). All animals were tolerant in terms of their inability to produce CTL to the relevant determinants, and to induce GvH in lethally irradiated F₁ recipients. Nevertheless, some mice also showed a normal MLC proliferative response and contained antigen-specific serum inhibitory factors, while other mice contained apparently antigen-specific suppressor cells. The pool of the latter, furthermore, was expanded considerably upon adoptive transfer of tolerant cells (with tolerizing antigens) to lethally irradiated syngeneic recipients. The data are compatible with the notion that suppression of clonal expansion represents the primary mechanism of tolerance maintenance (induction), and that the infrequently observed serum reactivity in such tolerant mice represents a vestige of the means whereby cell-mediated suppression was induced.