Analysis of natural killer cells isolated from human decidua: Evidence that 2B4 (CD244) functions as an inhibitory receptor and blocks NK-cell function.
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 CD56(bright) 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.
Vacca
Paola
P
Dipartamento di Oncologia, Biologia e Genetica, University of Genoa, Italy.
Pietra
Gabriella
G
Falco
Michela
M
Romeo
Elisa
E
Bottino
Cristina
C
Bellora
Francesca
F
Prefumo
Federico
F
Fulcheri
Ezio
E
Venturini
Pier Luigi
PL
Costa
Mauro
M
Moretta
Alessandro
A
Moretta
Lorenzo
L
Mingari
Maria Cristina
MC
D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology*; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D003656:Decidua / Q000166:cytology / Q000196:embryology / Q000276:immunology*; D005260:Female; D005333:Fetus / Q000196:embryology / Q000276:immunology; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D011247:Pregnancy / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology*; D022142:Secretory Vesicles / Q000276:immunology / Q000378:metabolism; D000071176:Signaling Lymphocytic Activation Molecule Family
D015703:Antigens, CD; D000943:Antigens, Differentiation; C084093:CD244 protein, human; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family