Effector functions of human decidual NK cells in healthy early pregnancy are dependent on the specific engagement of natural cytotoxicity receptors

被引:67
作者
El Costa, Hicham [1 ,2 ]
Tabiasco, Julie [1 ,2 ]
Berrebi, Alain [1 ,3 ]
Parant, Olivier [1 ,3 ]
Aguerre-Girr, Maryse [1 ,2 ]
Piccinni, Marie-Pierre [4 ,5 ]
Le Bouteiller, Philippe [1 ,2 ,3 ]
机构
[1] Inst Natl Sante & Rech Med, U563, F-31300 Toulouse, France
[2] Univ Toulouse 3, F-31077 Toulouse, France
[3] Hop Paule Viguier, Serv Gynecol Obstet, Ctr Hosp Univ, F-31059 Toulouse, France
[4] Univ Florence, Ctr Excellence Res Transfer & High Educ DENOTHE, I-50134 Florence, Italy
[5] Dept Internal Med, I-50134 Florence, Italy
关键词
NCR; NK; Decidua; Trophoblast; CLASS-I MOLECULES; KILLER-CELLS;
D O I
10.1016/j.jri.2009.06.123
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Natural killer (NK) cells represent the major lymphocyte population in the decidua basalis of the human uterus during healthy early pregnancy. The activity of decidual NK (dNK) cells and their activation status are different from those of peripheral blood (PB)-NK cells; i.e. dNK cells exhibit a unique phenotype. Decidual NK cells have been defined as CD56(bright), CD16(neg), and more recently CD160(neg). They express a unique repertoire of NK cell receptors, identical among all donors tested. Decidual NK cells express in particular NKp46-, NKp30- and NKp44-activating receptors, contrasting with PB-NK cells which are devoid of NKp44-activating receptors. Specific engagement of each of these three so-called natural cytotoxicity receptors in dNK cells has important functional consequences in terms of cytokine, chemokine and angiogenic factor secretion as well as cytotoxic potential. Strikingly, and in contrast with PB-NK cells, engagement of NKp46- but not NKp30-activating receptor on freshly isolated dNK cells triggers cytotoxicity. Such cytotoxic potential of dNK cells is negatively controlled by NKG2A inhibitory receptor co-engagement. This suggests that in situ, dNK cells cannot kill trophoblast cells during normal pregnancy. Whether such NKG2A-mediated inhibition is abolished during pregnancies complicated by pathologies including viral infection is an interesting hypothesis that remains to be tested. (C) 2009 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:142 / 147
页数:6
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