title: The HLA-G cycle provides for both NK tolerance and immunity at the maternal-fetal interface.
abstract: The interaction of noncytotoxic decidual natural killer cells (dNK) and extravillous trophoblasts (EVT) at the maternal-fetal interface was studied. Confocal microscopy revealed that many dNK interact with a single large EVT. Filamentous projections from EVT enriched in HLA-G were shown to contact dNK, and may represent the initial stage of synapse formation. As isolated, 2.5% of dNK contained surface HLA-G. However, surface HLA-G-negative dNK contained internalized HLA-G. Activation of dNK resulted in the disappearance of internalized HLA-G in parallel with restoration of cytotoxicity. Surface HLA-G was reacquired by incubation with EVT. This HLA-G cycle of trogocytosis, endocytosis, degradation, and finally reacquisition provides a transient and localized acquisition of new functional properties by dNK upon interaction with EVT. Interruption of the cycle by activation of dNK by cytokines and/or viral products serves to ensure the NK control of virus infection at the interface, and is illustrated here by the response of dNK to human cytomegalo virus (HCMV)-infected decidual stromal cells. Thus, the HLA-G cycle in dNK can provide both for NK tolerance and antiviral immunity.
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138; tilburgs@fas.harvard.edu jlstrom@fas.harvard.edu.
authors.forename: Tamara
authors.initials: T
authors.lastname: Tilburgs
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138;
authors.forename: J Henry
authors.initials: JH
authors.lastname: Evans
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138; Doctoral Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
authors.forename: Ângela C
authors.identifier: http://orcid.org/0000-0002-6731-8190
authors.initials: ÂC
authors.lastname: Crespo
authors.affiliation: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138; tilburgs@fas.harvard.edu jlstrom@fas.harvard.edu.
authors.forename: Jack L
authors.initials: JL
authors.lastname: Strominger
mesh_terms: D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D003586:Cytomegalovirus Infections / Q000276:immunology*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D059951:HLA-G Antigens / Q000378:metabolism*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D018613:Microscopy, Confocal; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014327:Trophoblasts / Q000276:immunology*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D059951:HLA-G Antigens
keywords: HCMV; cytotoxicity; decidua; human; pregnancy