International Immunology Advance Access originally published online on September 23, 2008
International Immunology 2008 20(11):1395-1405; doi:10.1093/intimm/dxn105
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Regulatory role of NKp44, NKp46, DNAM-1 and NKG2D receptors in the interaction between NK cells and trophoblast cells. Evidence for divergent functional profiles of decidual versus peripheral NK cells
1 Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, Genova, Italy
2 Istituto Giannina Gaslini, Dipartimento Immunologia Clinica e Sperimentale, Genova, Italy
3 Centro di Eccellenza per la Ricerca Biomedica, Università degli Studi di Genova, Genova, Italy
4 Dipartimento di Discipline Chirurgiche, Morfologiche e Metodologie Integrate, Università degli Studi di Genova, Genova, Italy
5 Istituto Nazionale per la Ricerca sul Cancro, Dipartimento Medicina Traslazionale Oncologica, Genova, Italy
Correspondence to: L. Moretta; E-mail: lorenzomoretta{at}ospedale-gaslini.ge.it
During the first trimester of pregnancy NK cells represent >50% of the lymphoid cells present in the human decidua where they reside in close contact with trophoblast cells. Because in decidual tissues NK cell activation and function may be induced by this interaction, we analyzed the cellular ligands recognized by activating NK receptors expressed on trophoblast cells. We show that these cells primarily express the NKp44 and DNAM-1 ligands and that interaction between these ligands and their corresponding receptors results in NK cell triggering. While activated peripheral blood NK (pNK) cells lysed the trophoblast cell lines JAR and JEG3, decidual NK (dNK) cells did not. On the other hand, they released VEGF, SDF-1, IP10 and large amounts of IL-8. Interaction with K562 target cells was exploited to induce optimal NK cell triggering, allowing a parallel, quantitative assessment of both cytolytic activity and cytokine production elicited by dNK cells. While dNK cells were unable to kill K562 even at high effector:target (E:T) ratios, they released large amounts of IL-8 also at low E:T ratios, a scenario compatible with dNK trophoblast cells interaction occurring within decidual tissues.
Keywords: angiogenetic cytokines in pregnancy, decidual NK cells, DNAM-1, innate immunity in pregnancy, NKp44, NKp46, NKG2D, trophoblast cells
Transmitting editor: E. Vivier
Received 21 June 2008, accepted 5 August 2008.
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