MATERNAL ANTI-PLACENTAL REACTIVITY IN NATURAL, IMMUNOLOGICALLY-MEDIATED FETAL RESORPTIONS

Observations on maternal recognition of the fetus and the demonstratio n of the effects of cytokines on reproductive events led to the ''immu notrophism'' model, which suggests that maternal immune recognition of fetally-derived Ags results in the release of cytokines that promote the growth of the placenta; any disturbance in this balance of cytokin es could result in deleterious consequences for the placenta and, in t urn, the fetus. We have focused our attention on the murine CBA/J x DB A/2 model of spontaneous abortions and compared them with normal CBA x BALB/c pregnancies. Our results indicate that the extent of stimulati on of maternal strain lymphocytes in response to stimulator placental cells in mixed lymphocyte-placenta reactions (MLPR) was much higher in the normal mating combination compared with the abortion-prone mating combination. Cytokine analysis of the supernatants from MLPR indicate s that there is significantly higher production of TNF-alpha, IFN-gamm a, and IL-2 in supernatants from the abortion-prone combination than i n supernatants from the normal combination. Furthermore, MLPR-stimulat ed cells induce resorptions in normal pregnant mice; maternal strain l ymphocytes stimulated by placentas from the abortion-prone combination induce high rates of fetal resorptions, but lymphocytes stimulated wi th placentas from the normal combination do not. Together, these resul ts suggest that immunologically mediated fetal resorptions probably re sult from improper or inappropriate maternal responses to placental Ag s. Our observations also suggest that such effects are probably mediat ed by cytokines.