S. Tangri et al., MATERNAL ANTI-PLACENTAL REACTIVITY IN NATURAL, IMMUNOLOGICALLY-MEDIATED FETAL RESORPTIONS, The Journal of immunology, 152(10), 1994, pp. 4903-4911
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.