Effect of the progesterone-induced serpin-like proteins of the sheep endometrium on natural-killer cell activity in sheep and mice.

Natural killer (NK)-like cells have been implicated as an important component of the endometrial lymphoid cell population and have been suggested to play roles in resistance to viral infection, in abortion, and in fetal growth. Inhibition of endometrial NK cell activity may be an important aspect of successful pregnancy because of the potential for actions directed against the conceptus. The aim of the study reported here was to test the hypothesis that the uterine milk proteins (UTM-proteins) inhibit activity of NK cells. Physiological concentrations of enriched preparations of UTM-proteins, which are a pair of related proteins that represent the major lymphocyte-inhibitory molecules in uterine fluid of pregnant and progesterone-treated ewes, were found to inhibit cytotoxic activity of cultured sheep and mouse NK cells. Furthermore, injection of the proteins into mice reduced activity of basal and poly(I).poly(C)-induced NK activity in spleen and prevented a slight increase in fetal loss caused by injection of poly(I).poly(C). These results further implicate the UTM-proteins as important regulators of uterine immune function.