title: Analysis of natural killer cells isolated from human decidua: Evidence that 2B4 (CD244) functions as an inhibitory receptor and blocks NK-cell function.
abstract: While during the first trimester of pregnancy natural killer (NK) cells represent the most abundant lymphocyte population in the decidua, their actual function at this site is still debated. In this study we analyzed NK cells isolated from decidual tissue for their surface phenotype and functional capability. We show that decidual NK (dNK) cells express normal surface levels of certain activating receptors, including NKp46, NKG2D, and 2B4, as well as of killer cell immunoglobulin-like receptors (KIRs) and CD94/NKG2A inhibitory receptor. In addition, they are characterized by high levels of cytoplasmic granules despite their CD56(bright) CD16- surface phenotype. Moreover, we provide evidence that in dNK cells, activating NK receptors display normal triggering capability whereas 2B4 functions as an inhibitory receptor. Thus, cross-linking of 2B4 resulted in inhibition of both cytolytic activity and interferon-gamma (IFN-gamma) production. Clonal analysis revealed that, in the majority of dNK cell clones, the 2B4 inhibitory function is related to the deficient expression of signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) mRNA. Moreover, biochemical analysis revealed low levels of SAP in the dNK polyclonal population. This might suggest that dNK cells, although potentially capable of killing, are inhibited in their function when interacting with cells expressing CD48.
authors.affiliation: Dipartamento di Oncologia, Biologia e Genetica, University of Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Vacca
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pietra
authors.forename: Michela
authors.initials: M
authors.lastname: Falco
authors.forename: Elisa
authors.initials: E
authors.lastname: Romeo
authors.forename: Cristina
authors.initials: C
authors.lastname: Bottino
authors.forename: Francesca
authors.initials: F
authors.lastname: Bellora
authors.forename: Federico
authors.initials: F
authors.lastname: Prefumo
authors.forename: Ezio
authors.initials: E
authors.lastname: Fulcheri
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Venturini
authors.forename: Mauro
authors.initials: M
authors.lastname: Costa
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000196:embryology / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D022142:Secretory Vesicles / Q000276:immunology / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; C084093:CD244 protein, human; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family