|
|
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.
Previous Article | Next Article 
Submitted April 14, 2006
Accepted August 3, 2006
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
Dipartimento di Oncologia, Biologia e Genetica, Univ. di Genova, Italy
Dipartimento di Medicina Sperimentale, Univ. di Genova, Italy
Istituto G. Gaslini, Genova, Italy
Istituto G. Gaslini and Univ. di Genova, Italy
Dipartimento di Discipline Chirurgiche, morfologiche e Metodologie integrate, Univ. di Genova, Italy
Struttura semplice di Diagnosi e Terapia dell'Infertilita, E.O. Ospedali Galliera, Genova, Italy
Dipartimento di Oncologia, Biologia e Genetica, Univ. di Genova and IST, Genova, Italy
* Corresponding author; email: lorenzomoretta{at}ospedale-gaslini.ge.it.
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 while 2B4 functions as an inhibitory receptor. Thus, cross-linking of 2B4 resulted in inhibition of both cytolytic activity and interferon- (IFN- ) 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 protein in 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.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
|
|