Moriya Gamliel2, Debra Goldman-Wohl1, Ronit Gilad1, Arbel Ben-David2, Caryn Greenfield1, Ronit Haimov-Kochman 1, Tal Imbar 1, Ofer Mandelboim2 and Simcha Yagel1,
1The Magda and Richard Hoffman Center for Human Placenta Research, Department of Obstetrics and Gynecology,2Lautenberg Center for Immunology,Hebrew University Hadassah Medical School, Jerusalem, Israel
Introduction: Natural killer (NK) cells, lymphocytes of the innate immune system, are able to kill tumor and infected cells. Recent studies suggest that NK cells possess some features of adaptive immunity including a certain type of immune cell memory, named trained immunity. During human pregnancy NK cells constitute the most abundant lymphocyte population (50-80%) found at the maternal fetal interface, the decidua. These NK cells (termed dNK) possess unique phenotypic and functional properties and are considered regulators of remodeling of the maternal fetal interface.
Methods: Here we investigate if the dNK cells have the ability to “remember” pregnancy. dNK cells were isolated from first trimester elective pregnancy terminations and the material was analyzed using RNA-seq.
Results: We observed that dNK cells from parous women express NKG2C in significantly higher percentages as compared with NK cells from nulliparous women. Analysis of the RNA-seq results revealed an upregulation of various genes related to angiogenesis, tissue remodeling, TH1 to TH2 shift, immune modulation, growth factors production, and NK recruitment. For the most highly expressed genes we validated the results also by real-time PCR assay.
Conclusions: Thus, we report for the first time that dNK cells display a trained immune response upon a second encounter with a semi-allogeneic fetus. This finding may give insight to the etiology of preeclampsia with increased risk in first pregnancy.