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Blood, 15 December 2006, Vol. 108, No. 13, pp. 4078-4085.
Prepublished online as a Blood First Edition Paper on August 24, 2006; DOI 10.1182/blood-2006-04-017343.


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IMMUNOBIOLOGY

Analysis of natural killer cells isolated from human decidua: evidence that 2B4 (CD244) functions as an inhibitory receptor and blocks NK-cell function

Paola Vacca, Gabriella Pietra, Michela Falco, Elisa Romeo, Cristina Bottino, Francesca Bellora, Federico Prefumo, Ezio Fulcheri, Pier Luigi Venturini, Mauro Costa, Alessandro Moretta, Lorenzo Moretta, and Maria Cristina Mingari

From the Dipartamento di Oncologia, Biologia e Genetica, University of Genoa, Italy; the Dipartimento di Medicina Sperimentale, University of Genoa, Italy; the Instituto Giannina Gaslini, Genoa, Italy; the Dipartimento di Ginecologia ed Ostetricia, University of Genoa, Italy; the Dipartimento di Discipline Chirurgiche, Morfologiche e Metologie Integrate, University of Genoa, Italy; the Struttura Semplice di Diagnosi e Terapia dell'Infertilità, Ente Ospedaliero Ospedali Galliera, Genoa, Italy; the Centro di Eccelenza per la Ricerca Biomedia, University of Genoa, Italy; and the Istituto Nazonale per la Ricerca sul Cancro, Genoa, Italy.

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-{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.


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