Moriya Gamliel, PhD1, Debra Goldman-Wohl, PhD2, Ronit Gilad, MD2, Caryn Greenfield, MSc2, Simcha Yagel, MD2 and Ofer Mandelboim, PhD1.
1Lautenberg Center for Immunology, Hebrew University Hadassah Medical School, Jerusalem, Israel
2Magda and Richard Hoffman Center for Placenta Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
Introduction: Natural killer (NK) cells are lymphocytes of the innate immune system 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. During human pregnancy NK cells constitute the most abundant lymphocyte population (50-70%) found in the point of contact between the mother and the baby: the decidua. These decidual NK (dNK) cells possess unique phenotypical and functional properties and are considered regulators of remodeling of the maternal fetal interface. Here we investigate if the dNK cells have the ability to “remember” pregnancy.
Methods: FACS analysis was performed on dNK cells for NK cell receptors, among other factors. We performed RNAseq analysis on the NKG2C+ dNK cells for various genes related to angiogenesis, immune modulation and growth factors production. For the most highly expressed genes, results were also validated by real-time PCR.
Results: Among the factors examined, we observed in particular expansion of NKG2C+ dNK population in parous women. dNK cells from parous women express NKG2C in significantly higher percentages as compared with NK cells from nulliparous women. In NKG2C+ cells we observed an upregulation of various genes related to angiogenesis, immune modulation and growth factors production, validated by real-time PCR. These results were independent of maternal CMV immunity status.
Conclusions: We report that dNK cells display a memory response and that this specific subpopulation of NK cells is expanded 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.