母児間の免疫応答系の異常からみた妊娠中毒症ならびに子宮内胎児発育遅延の病因病態 (<シンポジウム>2. 母児間免疫応答の異常)

概要

論文の詳細を見る
Recent emerging evidence suggests that the disruption of immune regulation may be involved in the pathophysiology of preeclampsia, habitual abortion and intrauterine growth restriction (IUGR). In this study, we tried to gain insight into the immunological aspects or these pregnant complications, especially from the viewpoint of the function of human leukocyte antigen (HLA)-G. 1. Structure and function of HLA-G. a) HLA-G has been reported to exhibit extremely low polymorphism in Caucasians. In a Japanese population, we found a new allele, G^*0104, having a non-synonymous amino acid substitution in the exon 3, which was the most common allele in a Japanese population. b) A soluble protein form of HLA-G was expressed by the translation of alternatively spliced messenger ribonucleic acid containing intron 4. c) HLA-G protein was detected in amniotic fluid at concentrations of 275ng/ml (median value). d) Expression of HLA-G on the target cells reduced their susceptibility to cytotoxic effector cells, suggesting that HLA-G protein on the trophoblasts may defend trophoblasts from the attack of maternal killer cells. e) Presence of HLA-G expressing cells modulates the ability of peripheral blood mononuclear cells (PBMCs) to release cytokines in favor of maintaining pregnancy. f) Lymphocytes in decidual tissue as well as lymphocytes in peripheral blood expressed the natural killer (NK) receptors which were reported to interact with HLA-G protein. 2. Immunological aspects of the pathophysiology of preeclampsia. a) In preeclampsia, the expression of HLA-G protein on the extravillous trophoblasts was attenuated and interleukin (IL)-2 was present in the decidual tissue, suggesting the involvement or perturbed local immune-regulation in the pathophysiology of preeclampsia. b) The serum concentrations of both IL2 and TNF-α in the first trimester of the preeclamptic group were significantly higher than those of the control group. The perturbation of feto-maternal immune regulation may precede the clinical manifestation of preeclampsia, which may be of relevance in the development of preeclampsia. c) The proliferation of HLA-G-positive trophoblastic cell line was not influenced by the addition of IL2, whereas a HLA-G-negative trophoblastic cell line exhibited significantly decreased proliferation when cultured with IL-2. The expression of HLA-G may commit trophoblasts to evade cell damage by IL2, which may be relevant to maternal tolerance of the fetus during pregnancy and its derangement as exemplified by preeclampsia. d) Trophoblasts pretreated with IL-2 or non-activated lymphocytes released angiogenic factor similar to those without pretreatment. However, trophoblasts pretreated with lymphokine activated killer (LAK) cells released less angiogenic factor compared with those without pretreatment. IL-2 expressed in preeclamptic decidua might reduced the angiogenic substances arising from trophoblasts by inducing LAK cells from decidual lymphocytes, which might be relevant to deranged vasculature of the placenta, a characteristic histology in preeclampsia. 3. Immunological aspects of the pathophysiology of habitual abortion. a) PBMCs from habitual aborters spontaneously secreted IL-2, suggesting that helper T cells were activated in these patients. A recent finding of an elevation in NK cell activity in habitual aborters can be explained by the induction of LAK cells by IL-2 secreted from activated helper T cells. b) The frequency of each HLA-G-allele in habitual aborters and their husbands did not significantly differ from that of healthy individuals, and no mutation was found in any affected couple. HLA-G allelic abnormality seemed to have little, if any, implication in the pathogenesis of habitual abortion. c) PBMCs from women with recurrent abortion exhibited an aberrant reaction to release cytokines upon the direct contact of HLA-G expressing cells, which may impact negatively on trophoblastic growth and may be pathogenic in habitual abo
社団法人日本産科婦人科学会の論文
1999-08-01

母児間の免疫応答系の異常からみた妊娠中毒症ならびに子宮内胎児発育遅延の病因病態 (<シンポジウム>2. 母児間免疫応答の異常)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク