Immunological roles of human leukocyte antigens (HLA) expressed on the trophoblasts in maintaining pregnancy.

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The object of this research project was to clarify the immunological roles of human leukocyte antigen (HLA) expressed on the trophoblasts to maintain pregnancy. We have performed 4 studies as follows.1)Immunological roles of soluble HLA-G (sHLA-G) protein in maintaining pregnancy.sHLA-G protein counterbalances membrane-bound HLA-G (mHLA-G) by shifting the balance of T helper (Th)1/Th2 cytokines secreted by peripheral mononuclear cells (PBMCs) to Thl polarization. However, sHLA-G protein modulated the release of cytokines from decidual mononuclear cells (DMCs) additively to mHLA-G by shifting-the Thl/Th2 balance to Th2 polarization.SHLA-G did not affect the natural killer activity of PBMCs.2)Immunological roles of HLA-E in maintaining pregnancy.HLA-E suppressed the release of tumor necrosis factor (TNF)-α from PBMCs additively to mHLA-G but enhanced the release of interferon (IFN)-γ contrary to mHLA-G.3)Effects of herbal medicines on the immune reaction of patients with autoimmunity related recurrent abortion.Herbal medicines, Tokishakuyaku-san and Sairei-To, enhanced the secretion of Thi cytokines from PBMCs but (lid not affect the cytokine secretion from DMCs. These data provided the rationale of herbal medicines in the treatment of autoimmunity related recurrent abortion.4)A primary cell culture system for human cytotrophoblasts.We have established a novel cell culture system for highly purified human cytotrophoblasts enabling in vitro acquisition of extra-villous phenotype. The cultured trophoblasts gradually upregulated HLA-G along with the differentiation to extra-villous phenotype