TY - JOUR
T1 - Analysis of natural killer cells isolated from human decidua
T2 - Evidence that 2B4 (CD244) functions as an inhibitory receptor and blocks NK-cell function
AU - Vacca, Paola
AU - Pietra, Gabriella
AU - Falco, Michela
AU - Romeo, Elisa
AU - Bottino, Cristina
AU - Bellora, Francesca
AU - Prefumo, Federico
AU - Fulcheri, Ezio
AU - Venturini, Pier Luigi
AU - Costa, Mauro
AU - Moretta, Alessandro
AU - Moretta, Lorenzo
AU - Mingari, Maria Cristina
PY - 2006/12/15
Y1 - 2006/12/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2006-04-017343
DO - 10.1182/blood-2006-04-017343
M3 - Article
C2 - 16931625
AN - SCOPUS:33845494463
VL - 108
SP - 4078
EP - 4085
JO - Blood
JF - Blood
SN - 0006-4971
IS - 13
ER -