Analysis of natural killer cells isolated from human decidua: evidence that 2B4 (CD244) functions as an inhibitory receptor and blocks NK-cell function
- 15 December 2006
- journal article
- Published by American Society of Hematology in Blood
- Vol. 108 (13), 4078-4085
- https://doi.org/10.1182/blood-2006-04-017343
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 CD56bright 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-γ (IFN-γ) 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.Keywords
This publication has 34 references indexed in Scilit:
- Identification of effector-memory CMV-specific T lymphocytes that kill CMV-infected target cells in an HLA-E-restricted fashionEuropean Journal of Immunology, 2005
- Molecular Dissection of 2B4 Signaling: Implications for Signal Transduction by SLAM-Related ReceptorsMolecular and Cellular Biology, 2004
- Human Decidual Natural Killer Cells Are a Unique NK Cell Subset with Immunomodulatory PotentialThe Journal of Experimental Medicine, 2003
- Natural killer cells, viruses and cancerNature Reviews Immunology, 2001
- Activating Receptors and Coreceptors Involved in Human Natural Killer Cell-Mediated CytolysisAnnual Review of Immunology, 2001
- Signaling pathways engaged by NK cell receptors: double concerto for activating receptors, inhibitory receptors and NK cellsSeminars in Immunology, 2000
- Identification and Molecular Characterization of Nkp30, a Novel Triggering Receptor Involved in Natural Cytotoxicity Mediated by Human Natural Killer CellsThe Journal of Experimental Medicine, 1999
- p46, a Novel Natural Killer Cell–specific Surface Molecule That Mediates Cell ActivationThe Journal of Experimental Medicine, 1997
- Effect of superantigens on human thymocytes: selective proliferation of Vβ2+ cells in response to toxic shock syndrome toxin-1 and their deletion upon secondary stimulationInternational Immunology, 1996
- Differential Expression of Adhesion and Homing Molecules by Human Decidual and Peripheral Blood Lymphocytes in Early PregnancyCellular Immunology, 1994