Inheritance of acquired immunological tolerance to foreign histocompatibility antigens in mice

CBA mice were rendered tolerant of major histocompatibility antigens of A/J mice by neonatal injection of 100 x 10(6) lymphoid cells of (CBA X A/J)F1 followed by repeated injections of F1 cells at 2-week intervals throughout the study. When adult (8 weeks old), 10 tolerant or normal CBA males were mated to normal CBA females. Spleen cells of the progeny were tested for their ability to mount a cytotoxic T lymphocyte response in vitro against A/J antigens or against C57BL/6J and B10.A (2R) antigens in a cell-mediated lympholysis (CML) assay. A significant proportion (50-60%) of first-generation offspring of tolerant fathers failed to produce detectable anti-A/J cytotoxic responses but responded in the normal range to stimulation by C57BL/6J or B10.A (2R). Second-generation offspring derived from mating animals born of tolerant male parents--either brother x sister matings (incross or matings to normal CBA mice (outcross)--also showed a high proportion (20-40%) with diminished anti-A/J CML responses when similarly tested in vitro. Thus, a specific acquired somatic characteristic in the immune system (tolerance to major histocompatibility antigens) induced in male mice shows significant transmission to first- and second-generation offspring.