Estudio de las moléculas relacionadas con la tolerancia inmunológica hla-g e indolamina 2,3-dioxigenasa durante el embarazo

Resumen

ESTUDIO DE LAS MOLÉCULAS RELACIONADAS CON LA TOLERANCIA INMUNOLOGICA HLA-G E INDOLAMINA 2,3-DIOXIGENASA DURANTE EL EMBARAZO #RESUMEN: Although the foetus can be considered a semi-allogeneic graft, it is not rejected by maternal immune system because a materno-fetal tolerance is established. some of the mechanisms involved in this toierance are HLA-G molecule, indoleamine 2,3-dioxygenase (IDO) enzyme, Fas /Fas-L pro-apoptotic sytem, Leukemia inhibitory Factor LIF).The aim of this work was to analyze the evolution of these parameters along the pregnancy, investigate if they could be used to predict a miscarriage and investigate the regulation of HLA-G functionality by no, a free radical present in placenta. We observed that plasmatic HLA-G (sHLA-Gl + HLA-G5) concentrations increase in pregnancy. This increase occurs during the first term, with a peak in the third month of pregnancy. There is no increase in HLA-G5 plasmatic leveis, so HLA-G increase in plasma is due to sHLA-Gl isoform. we have found that during pregnancy there is a significant increase in HLA-G expression by maternal monocytes. Monocytes from pregnant women become more susceptible to HLA-G expression induction by iFN-á. in dendritic cells there is no HLA-G expression at cell surface during pregnancy, but there is a higher HLA-G release to the medium that is al so due to sHLA-Gl isoform. we observed during pregnancy a correlation between the percentage of monocytes that expressed HLA-G and the percentage of T lymphocytes that were cytotoxic. in maternal matured dendritic cells, we observed a decrease in CD40 and C80 cell surface expressions, that can be considered tolerogenic mechanisms. There is also a decrease in CD95 expression, making these cells less susceptible to apoptosis by Fas system. Related with ido, pregnancy did not change monocytic activity and there was no change in plasmatic kynurenine/tryptophan ratio. So ido activity can not be used as a marker of materno-fetal tolerance, LlF can regulate materno-fetal tolerance molecules inhibiting ido activity by a post-transcriptional mechanism and increasing HLA-G release to the medium. we observed that plasmatic HLA-G leveis during the second month of pregnancy in women who suffered a subsequent miscarriage were much lower than women with a successful pregnancy, and even lower than non-pregnant women. So plasmatic HLA-G leveis couid be use as risk marker of subsequent miscarriages. NO can modulate the activity of several molecules, some of them, such as ido, implicated in maternal-fetal tolerance. We investigated if NO can regulate HLA-G functionality. we observed that treatment of HLA-G with NO donors did no affect HLA-G capability to inhibit NK cells citotoxicty, allogeneic T cell proliferation or cytokines-mediated T cell proliferation