Interferon-gamma contributes to the normalcy of murine pregnancy

Uterine natural killer (uNK) cells are transient, large, heavily granulated , maternal lymphocytes present on the mesometrial side of the pregnant mous e uterus. These cells contribute to normal implantation site development. C ytokine production, particularly interferon (IFN)-gamma, is a major functio n of most NK cell subsets. In this study, uNK cells were assessed for IFN-g amma production. Local concentrations of IFN-gamma were measured in the mes ometrial regions of murine implantation sites between Days 6 and 16 of gest ation. IFN-gamma was detected by ELISA at all days studied in a random-bred (CD1) and an inbred (BALB/c) strain of immune-competent mouse and in two i mmune-deficient strains, SCID (NK+, T-, B-) and tg epsilon 26 (NK-,T-, B+). Concentrations of IFN-gamma per implantation site peaked at Day 10 of gest ation in NK+ strains but were low and relatively constant in NK- mice. To e valuate the functions of IFN-gamma at murine implantation sites, pregnancy was studied in homozygously mated IFN-gamma(-/-) and IFN-gamma R alpha(-/-) mice and their congenic controls. Primiparous but not multiparous IFN-gamm a(-/-) mice experienced significant fetal loss. Primiparous IFN-gamma R alp ha(-/-) carried full litters to term. Implantation site pathology was demon strated in both strains of gene-deleted mice by light microscopy and ultras tructurally. This included elevated numbers of uNK cells that contained few er and smaller granules and, after Day 10 of gestation, progressive necrosi s and loss of decidua. The presence of a fetus able to produce IFN-gamma di d not modify the phenotype of pregnant IFN-gamma(-/-) mice. This study indi cates that during murine pregnancy, uNK cells are the main source of IFN-ga mma on the mesometrial side of the uterus and that IFN-gamma contributes to normal health of the midgestational decidua. Furthermore, evidence is pres ented that IFN-gamma-producing cells exist in mesometrial regions of implan tation sites that are neither NK nor T cells.