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, Maria Cristina Mingari

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)4078-4085
Number of pages8
JournalBlood
Volume108
Issue number13
DOIs
Publication statusPublished - Dec 15 2006

ASJC Scopus subject areas

  • Hematology

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