Uterine natural killer cells are targets for a trophoblast cell-specific cytokine, prolactin-like protein A

PRL-like protein A (PLP-A) is a member of the PRL family expressed in troph oblast cells coincident with establishment of the chorioallantoic placenta. The purpose of this investigation was to identify targets for PLP-A. Using an alkaline phosphatase-tagging strategy, we show that PLP-A specifically interacts with a population of natural killer (NK) lymphocytes within the m esometrial compartment of decidua from pregnant and pseudopregnant rats. Th ese observations are supported by the codistribution of PLP-A targets with cells expressing the rat NK cell surface marker, gp42, the absence of PLP-A binding in conceptuses from NK cell-deficient tg epsilon 26 mice, and the specific interaction of PLP-A with a rat NK cell line, RNK-16. We have furt her demonstrated that PLP-A effectively suppresses RNK-16 cell cytolytic ac tivities. Our results provide evidence for a new paradigm of embryonic-mate rnal communication involving a PLP-A signaling pathway between trophoblast cells and uterine NK lymphocytes.