A possible maternal effect in the abnormal hyporesponsiveness to specific alloantigens in offspring born to neonatally tolerant fathers.

Newborn CBA mice were inoculated i.p. with 1 X 10(8) adult (CBA X A)F1 lymphoid cells with 5 X 10(7) F1 hybrid lymphoid cells thereafter inoculated i.v. at 14-day intervals. The mice were subsequently grafted with A/J tail skin at 24 days of age. At 8 wk of age, individual tolerant males with intact skin grafts were each mated with similar tolerant skin-grafted females or with 8-wk-old control normal CBA females. Approximately 0.4 ml of peripheral blood from 7-wk-old progeny born to these crosses, along with the blood from age-matched progeny born to normal CBA incrosses, were used for in vitro mixed leukocyte cultures (MLC). All progeny received skin grafts of (CBA X A)F1 tail skin at 7 1/2 wk of age. In this study, we show i) that MLC hyporesponsiveness to histocompatible cells is an acquired phenotype expressed by lymphoid cells of the progeny of tolerant male mice, and ii) that these progeny also show delayed rejection of (CBA X A)F1 skin grafts. The continued breeding of the first generation animals established that a similar transmission of hyporesponsiveness can be observed in the second generation progeny. When putatively normal females, however, which had borne several litters after mating with neonatally tolerant males, were mated with "normal" (nontolerant) males; their offspring also exhibited a specific hyporesponsiveness in MLC to the initial tolerizing allodeterminants. This suggests that there may ultimately be a maternally derived origin for the transmission of characters from tolerant males.