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3 April 2013 Maternal Decidual Macrophages Inhibit NK Cell Killing of Invasive Cytotrophoblasts During Human Pregnancy
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Human pregnancy is an immunological paradox. Semiallogeneic (fetal) placental cells (extravillous cytotrophoblasts [CTBs]) invade the uterine lining (decidua), which contains a unique decidual natural killer (dNK) cell population, identified by the cell surface phenotype CD56bright CD16 CD3 and CD14 CD206 macrophages (dMac). Previous reports suggested that human dNK cells are not a threat to the fetoplacental unit because they are anergic. In contrast, here we showed that purified and exogenously stimulated dNK cells are capable killers of cellular targets, including semiallogeneic CTBs. However, dMacs in the decidual leukocyte (DL) population restrained dNK killing through a transforming growth factor beta1 (TGF-beta1)-dependent mechanism. Our findings support a new model whereby dNK cells, capable of killing CTBs, are prevented from doing so by neighboring macrophages, thus protecting the fetal cells from NK cell attack. We speculate that this mechanism would inhibit dNK cell-mediated killing, even under conditions where high levels of cytokines may stimulate dNK cells, which could pose a threat to the developing placenta.

Elizabeth C. Co, Matthew Gormley, Mirhan Kapidzic, David B. Rosen, Marvin A. Scott, Haley A.R. Stolp, Michael McMaster, Lewis L. Lanier, Alicia Bárcena, and Susan J. Fisher "Maternal Decidual Macrophages Inhibit NK Cell Killing of Invasive Cytotrophoblasts During Human Pregnancy," Biology of Reproduction 88(6), (3 April 2013).
Received: 26 January 2012; Accepted: 1 March 2013; Published: 3 April 2013

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