Therapy with dendritic cells influences the spontaneous resorption rate in the CBA/J x DBA/2J mouse model.

Abstract

DBA/2J-mated CBA/J female mice are prone to a high incidence of fetal abortions. This fetal wastage can be dramatically reduced by immunizing the female mice with BALB/c, but not with DBA/2J spleen cells during early gestation. Nevertheless, the underlying mechanisms remain to be elucidated. Recently, dendritic cells (DC) have been described at the feto-maternal interface in the human uterus. In this work, we studied the effect of adoptive transfer of DC on the maintenance of pregnancy in the CBA/J x DBA/2J model. Bone marrow-derived DC were generated from virgin female CBA/J mice (6-8 weeks old). CBA/J females were inoculated with DC twice before mating. Four different experimental groups were included: (i) no treatment control, (ii) mice injected with culture medium [granulocyte-macrophage colony-stimulating factor (GM-CSF)], (iii) immunized with DC and (iv) immunized with paternal DBA/2J antigens lisate-pulsed DC, n = 5. The control abortion rate was 23.8%, and with GM-CSF alone was 17.6%. Following inoculation of syngeneic DC abortion rates were reduced to 2.2%, but protection was short-lived. Abortion rates with DC pulsed with DBA/2J antigens was 5%. Serum of interleukin (IL)-6 levels were lower in the latter two groups up to the time of abortion. The kinetics of immunoglobulin G asymmetric antibodies synthesis was modified, but there was no correlation between asymmetric antibodies production and the lowering of abortions rates. Syngeneic DC prevented abortions and this was linked to a decrease in IL-6 levels, but not with levels of asymmetric antibodies.