title: Inadequate tolerance induction may induce pre-eclampsia.
abstract: The fetus is semi-allograft to the maternal host; therefore, a system of tolerance must be present during pregnancy. Epidemiological findings support a relationship between pre-eclampsia and the failure of tolerance induction. For induction of major histocompatibility complex (MHC) class I-specific tolerance, long-term exposure to seminal fluid, which contains paternal soluble MHC class I antigens, may induce paternal MHC class I-specific tolerance. Furthermore, soluble HLA-G1, which induces the deletion of CD8(+) T-cells, and the combination of maternal killer-immunoglobulin-like receptors (KIR) on NK cells and fetal HLA-C, which affects the balance between inhibition and activation signals of NK cells, regulatory CD8(+) T cells, and regulatory NK cells, may play very important roles in the induction of MHC class I-specific tolerance. On the other hand, exposure to sperm, which express paternal HLA-DR, and trophoblastic debris, which contain intracellular fetal HLA-DR, may induce paternal MHC class II-specific tolerance. In this process, CD4(+)CD25(+) regulatory T (Treg)-cells play central roles. In this review, we discuss the relationship between the risk of pre-eclampsia and tolerance induction.
authors.affiliation: Department of Obstetrics and Gynecology, University of Toyama, 2630 Sugitani, Toyama, Japan; Center of Excellence (COE) 21st Program, Japan. s30saito@med.u-toyama.ac.jp
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Sakai
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Akitoshi
authors.initials: A
authors.lastname: Nakashima
authors.forename: Arihiro
authors.initials: A
authors.lastname: Shiozaki
mesh_terms: D005260:Female; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D011225:Pre-Eclampsia / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D054340:Receptors, KIR / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology / Q000378:metabolism
chemical_list: D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D054340:Receptors, KIR