Cell-mediated immunity and blocking serum activity to tolerated allografts in rats

Abstract

W/Fu rats were neonatally inoculated with bone marrow cells from B/N rats and vice versa. Of the inoculated rats, some were capable of accepting a foreign (B/N or W/Fu) skin graft over the period of observation (i.e. for more than 100 days), while other rats rejected their skin grafts as early as control animals (within 8-12 days) or after a prolonged period of acceptance (20-96 days). Using a microcytotoxicity test, it could be shown that both those rats that rapidly rejected skin grafts and those that kept their grafts during the observation period had lymphocytes capable of destroying cultivated allogeneic cells from the respective strains with whose cells the rats had been inoculated as newborns. The degree of lymphocyte reactivity decreased upon time, so that 4 of 13 rats that had carried "tolerated" skin grafts over more than 84 days had lymphocytes which were nonreactive in the highest dose tested, and the degree of reactivity in the other 9 rats was less than seen early after tolerance induction. Rats that were capable of accepting skin grafts over prolonged periods of time had sera that could specifically block lymphocyte-mediated cytotoxicity, while sera from rats that had rejected their grafts did not block. Sera from rats that rejected their skin grafts after 20-96 days lost the blocking activity 3-10 days before rejection.