title: Ex vivo functional responses to HLA-G differ between blood and decidual NK cells.
abstract: Restricted expression of human leucocyte antigen-G (HLA-G) to fetal extravillous trophoblast cells, which invade the decidua during implantation, suggests a role for HLA-G in placentation. In this study, we have investigated several aspects of HLA-G expression and function. Surface levels of HLA-G expression were measured in 70 normal pregnancies. We show the dimeric conformation that is unique to HLA-G forms after passage through the Golgi apparatus. Differences were found in the receptor repertoire of decidual natural killer (dNK) cells that express the leucocyte immunoglobulin-like receptor B1 (LILRB1), which binds dimeric HLA-G strongly. We then measured functional responses of dNK cells with LILRB1, when stimulated by HLA-G in both monomeric and dimeric conformations. Degranulation, interferon-γ and interleukin-8 production by dNK cells freshly isolated from the first trimester implantation site were either undetected or not affected by HLA-G. These findings should be considered when inferring the activity of tissue NK cells from results obtained with cell lines, peripheral NK or cultured dNK cells.
authors.affiliation: Department of Pathology and Center for Trophoblast Research, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Apps
authors.forename: Andrew
authors.initials: A
authors.lastname: Sharkey
authors.forename: Lucy
authors.initials: L
authors.lastname: Gardner
authors.forename: Victoria
authors.initials: V
authors.lastname: Male
authors.forename: Pippa
authors.initials: P
authors.lastname: Kennedy
authors.forename: Leanne
authors.initials: L
authors.lastname: Masters
authors.forename: Lydia
authors.initials: L
authors.lastname: Farrell
authors.forename: Des
authors.initials: D
authors.lastname: Jones
authors.forename: Rasmi
authors.initials: R
authors.lastname: Thomas
authors.forename: Ashley
authors.initials: A
authors.lastname: Moffett
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003656:Decidua / Q000166:cytology* / Q000276:immunology*; D005260:Female; D015236:HLA-C Antigens / Q000276:immunology; D059951:HLA-G Antigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011247:Pregnancy; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000276:immunology; D014327:Trophoblasts / Q000276:immunology
chemical_list: D015703:Antigens, CD; D015236:HLA-C Antigens; D059951:HLA-G Antigens; D016209:Interleukin-8; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D011971:Receptors, Immunologic; D007371:Interferon-gamma