Mitsuo Yokoyama

Actively Acquired Tolerance in Fetal‐Maternal Combinations: A Review**

Two hypotheses have been developed as partial explanations of the protective mechanisms involved in Rh hemolytic disease. The first is based on the observations of Levine and others that Rh erythroblastosis is less likely to arise when the ABO blood group of the mother is serologically incompatible with that of the fetus. According to this theory, fetal blood cells are rapidly destroyed by maternal iso‐antibodies and removed from her circulation before the sensitization has sufficient time to develop. The second, due to Owen, is based on the phenomenon of actively acquired tolerance. This theory asserts that maternal blood cells may enter the fetal blood stream during the critical period in which the organism “learns” to recognize its tissues as its own. Thus, an Rh negative fetus transfused in utero with Rh positive cells might be expected to be tolerant of further exposures to the Rh antigen in adult life. Owens data, based upon sensitization of the Rh negative mother show a distinct correlation with the Rh type of her mother. The available evidence is not sufficient to exclude one of the two hypotheses, and it is possible that both operate. The data for fetal‐maternal transfer of blood cells is far more conclusive than that for passage in the other direction. Definitive proof of tolerance to Rh antigens, however, requires further study.