The presence of DC-SIGN(+) cells during the menstrual cycle and their proliferation in early pregnancy suggests an important role of these cells with regard to the balance between defense against pathogens and tolerance of the fetal allograft. Whether the increase of CD83(+) mature DC and CD68(+) macrophages in the late secretory phase is caused by hormonal stimuli and/or is due to changes of the cytokine/chemokine micromilieu remains to be investigated.
Studying the proportion of decidual immune cells during pregnancy, we detected a unique pattern which could be useful to design novel therapies for pathological conditions during pregnancy.
BackgroundChanges in the balance of decidual leucocyte populations may lead to an unfavourable uterine microenvironment which may be associated with the development of preeclampsia (PE). In this study, we therefore investigated the leucocyte subpopulations in decidual tissues of 33 women with preeclampsia and 66 control patients.MethodsDecidua was either obtained via curettage during cesarean section or dissected from the surface of the basal plate of the placenta after spontaneous delivery. We used FACS analysis to quantify decidual leukocytes (CD45), NK cells (CD56+/CD16+ and CD56++/CD16-), antigen presenting cells (HLA-DR, DC-Sign, CD14) and T/B cells (CD8, CD4, alpha-beta-T-cell receptor, gamma-delta-T-cell receptor, CD25, CD19).ResultsThe number of decidual cytotoxic CD8+T-lymphocytes (P < 0.02), alpha-beta -T-cell receptor positive T cells (P < 0.03) and of CD56+/CD16+ NK cells (P < 0.03) was lower in decidua from women with PE than in decidua from control patients.ConclusionThe observed reduction of specific leucocyte subsets could create a microenvironment which is unfavourable for an appropriate placentation and could thereby be involved in the development of preeclamptic symptoms.
Our findings suggest that the female sex hormones hCG and E2 inhibit the T-cell stimulatory capacity of DCs, which may help in preventing an allogenic T-cell response against the embryo.
The observed pattern supports the role of decidua as a tissue which promotes angiogenesis, attracts monocytes and modulates the function of the latter.
We have identified MIC-1 as a novel factor (secreted by decidual cells in early pregnancy) that could promote the increase of a tolerogenic subtype of DC in decidua.
These findings suggest that ActA and InA interfere with selected aspects of DC maturation and may thereby help preventing activation of allogenic T-cells by the embryo. Thus, we have identified two novel members of the TGF-beta superfamily that could promote the generation of tolerance-inducing DCs.
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