Pregnancy-associated immunoregulatory molecules discovered in ruminants and their possible relevance to other species.

Several distinct molecules involved in maternal-conceptus interactions have been discovered in ruminants. Among these are two families of immunoregulatory molecules that represent genes that have undergone evolution to perform a function distinct from that of the ancestral gene. Interferon-tau (IFN-tau) is a product of the trophoblast that retains its antiviral activity and other functions characteristic of interferons but whose primary role is the inhibition of luteolysis. The uterine serpins are progesterone-induced members of the serpin superfamily of serine proteinase inhibitors. The uterine serpin has only a weak antiproteinase activity and, at least in the sheep, appears to function as an inhibitor of lymphocyte proliferation to mediate the immunosuppressive effects of progesterone on uterine immune function. The IFN-tau are not present in mammals that diverged from ancestors of ruminants before 36 million years ago, the approximate origin of IFN-tau, but uterine serpins apparently arose before the divergence of mammals and the proteins are present in at least one nonruminant species, the pig. The clinical value of these molecules can extend beyond use in ruminants. IFN-tau has been used to treat experimental allergic encephalomyelitis in mice and can inhibit human immunodeficiency virus replication. Ovine uterine serpin is also active against murine and human cells but a clinical use has not yet been identified.