Immunological role of HLA-G for maintaining pregnancy

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1. Polymorphism of HLA-G.We discovered a new allele of HLA-G which possessed a non-synonymous singlebase substitution in exon 3 compared with the previously reported alleles and was officially designated G**0104 by the WHO Nomenclature Committee. G**0104 was most common in Japanese population. In addition, we identified a single-base error in exon 2 in the sequence of G**01012 and corrected it.2. HLA-G and preeclampsia.The expression of HLA-G protein on the extravillous trophoblasts in placenta was attenuated in all the preeclamptic patients. All of these trophoblasts possessd IL-2 which was not observed in normal placenta. Further, serum concentrations of IL-2 in the first trimester of pregnancy in women who had preeclampsia develop after 28 weeks of pregnancy were higher than those of normal pregnant women. IL-2 in preeclamptic placenta might reduce the angiogenic substances arising from trophoblasts by inducing lymphokine activated killer cells from decidual lymphocytes, which might be relevant to deranged vasculature of the placenta, a characteristic histology in preeclampsia.3. Cytokine release from mononuclear cells and HLA-G on the target cells.Mononuclear cells, if cultured with HLA-G-expressing cells, increase their ability to release IL-3 which enhances the growth and development of trophoblasts and decrease TNF-alpha which suppresses the growth of trophoblasts.4. Natural killer receptor on the decidual lymphocytes.Decidual lymphocytes express the natural killer receptors which recognize HLA-G on the trophoblasts.