title: HLA-G in human early pregnancy: control of uterine immune cell activation and likely vascular remodeling.
abstract: Despite a number of controversies, the functional importance of human leukocyte antigen G (HLA-G) in early human pregnancy is now sustained by a large amount of sound data. Membrane-bound and soluble HLA-G isoforms, either as β2-microglobulin-free or -associated as monomers or dimers, are expressed by different trophoblast subpopulations, the only fetal-derived cells that are directly in contact with maternal cells (maternal-fetal interfaces). Trophoblast HLA-G is the specific ligand of multiple cellular receptors present in maternal immune and non-immune cells, including CD8, leukocyte immunoglobulin-like receptor (LILR) B1, LILRB2, killer cell immunoglobulin-like receptor (KIR) 2DL4, and possibly CD160. Trophoblast HLA-G specific engagement of these cellular receptors triggers either inhibitory or activating signals in decidual CD8 + T cells, CD4 + T cells, natural killer (NK) cells, macrophages, dendritic cells, or endothelial cells. Such HLA-G-receptor specific interactions first contribute to limit potentially harmful maternal anti-paternal immune response by impairment of decidual NK cell cytotoxicity, inhibition of CD4 + and CD8 + T-cell and B-cell proliferation, and induction of apoptosis of activated CD8 + T cells. Second, these HLA-G specific interactions contribute to stimulate placental development through secretion of angiogenic factors by decidual NK cells and macrophages, and to provide a protective effect for the outcome of pregnancy by the secretion of interleukin (IL)-4 by decidual trophoblast antigen-specific CD4 + T cells.
authors.affiliation: French National Institute of Health and Medical Research (INSERM UMR 1043), The National Center of Scientific Research (CNRS, UMR 5282), Toulouse III University, Toulouse Purpan Physiopathology Center, Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Le Bouteiller
mesh_terms: D017951:Antigen Presentation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D059951:HLA-G Antigens / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D011247:Pregnancy; D014599:Uterus / Q000276:immunology*; D066253:Vascular Remodeling / Q000276:immunology* / Q000502:physiology
chemical_list: D059951:HLA-G Antigens