Cellular mechanisms of the resistance to the induction of immunological tolerance.

Tolerance inducibility was examined in various strains of mice by injecting aggregate-free HGG, followed by challenge with aggregated HGG plus LPS and by assessing spleen PFC numbers. Marked differences were shown between C57BL/6 and DDD mice. The antibody response to HGG was totally suppressed in C57BL/6 mice injected with 0-1 to 1 mg of aggregate-free HGG whereas little suppresssion was observed in DDD mice. Cellular mechanisms of the resistance to tolerance induction in DDD mice were explored. On the injection of 1 mg of aggregate-free HGG, spleen cells were only partially tolerized (at minimum, 21 per cent of control level on 5th day) and thymus cells were suppressed to 40 per cent of the normal responsiveness. No suppression was observed in bone marrow cells. Macrophages do not seem to play a decisive role in the resistance to tolerance induction in DDD mice as the injection of biofiltered HGG or the pretreatment with carrageenan did not ease the resistance. From these data, it was suspected that the resistance to tolerance induction to HGG in DDD mice might be due to the raised threshold of T cells for tolerance.