Blois Sandra, Alba Soto Catalina D, Olmos Sofia, Chuluyan Eduardo, Gentile Teresa, Arck Petra C, Margni Ricardo A
IDEHU, Institute of Humoral Immunity Studies, National Council of Scientific and Technological Research (CONICET), University of Buenos Aires, Buenos Aires, Argentina.
Am J Reprod Immunol. 2004 Jan;51(1):40-8. doi: 10.1046/j.8755-8920.2003.00120.x.
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.
与DBA/2J雄鼠交配的CBA/J雌鼠容易出现高比例的胚胎流产。在妊娠早期用BALB/c脾细胞免疫雌鼠可显著减少这种胚胎丢失,但用DBA/2J脾细胞免疫则无效。然而,其潜在机制仍有待阐明。最近,在人类子宫的母胎界面发现了树突状细胞(DC)。在本研究中,我们探讨了过继转移DC对CBA/J×DBA/2J模型中妊娠维持的影响。
从6-8周龄的未交配CBA/J处女雌鼠中分离出骨髓来源的DC。CBA/J雌鼠在交配前两次接种DC。实验分为四组:(i)未处理对照组,(ii)注射培养基[粒细胞-巨噬细胞集落刺激因子(GM-CSF)]的小鼠,(iii)接种DC的小鼠,(iv)接种用父本DBA/2J抗原裂解物脉冲处理的DC的小鼠,每组n = 5。
对照组流产率为23.8%,单独使用GM-CSF组为17.6%。接种同基因DC后流产率降至2.2%,但保护作用短暂。用DBA/2J抗原脉冲处理的DC组流产率为5%。直到流产时,后两组的白细胞介素(IL)-6血清水平较低。免疫球蛋白G不对称抗体合成的动力学发生了改变,但不对称抗体的产生与流产率的降低之间没有相关性。
同基因DC可预防流产,这与IL-6水平降低有关,但与不对称抗体水平无关。