Ontogeny of acquired immunological tolerance to H-2 alloantigens.

The ontogeny of mixed lymphocyte reaction and cell-mediated lymphocytotoxicity (CML) responsiveness was studied in mice that had been neonatally tolerized by the injection of 15 X 10(6) semiallogeneic bone marrow and spleen cells, and compared to that of unprimed littermates. Spleen cells from primed mice did not develop reactivity towards the tolerizing antigen but did develop reactivity towards third-party alloantigens. Similarily, thymus cells from primed mice also failed to develop CML reactivity towards the tolerizing antigen. Thymus cell mixed lymphocyte reactivity, which was demonstrable in neonates before the tolerizing injection, declined rapidly between 2 and 4 days of age, compared to that of controls. Thus neonatal tolerance was shown to operate at least at a thymic, and perhaps pre-thymic level; measurement of the levels of chimeric cells in the thymus and bone marrow favored the latter interpretation.