An evaluation of the maternal natural killer cell population during the course of murine pregnancy.

Earlier work from this laboratory revealed an increase in the level of null (Thy-1-, IgM-) lymphocytes in the maternal lymphoid organs during the first pregnancy in the mouse that was more pronounced during allogeneic pregnancy than during syngeneic pregnancy. In view of the suggestive evidence for the bone marrow origin of these null cells, the functional significance of the null cell rise was explored in this study by an examination of (1) splenic NK activity as measured by the 51Cr-release assay using YAC-1 lymphoma targets, (2) the incidence of NK lineage cells in the spleen as measured by the ability of splenic null lymphocytes to bind YAC-1 lymphoma targets, and (3) the possible presence of a NK target structure on placental trophoblast cells, studied with a cold target competition assay. Results revealed that the absolute levels of null lymphocytes, NK lineage cells, and NK activity in the spleen increased moderately and nearly at the same time during syngeneic pregnancy. During allogeneic pregnancy all three parameters increased more significantly, the rise in the levels of NK activity and NK lineage cells somewhat preceding the null cell rise, suggesting preferential recruitment of active NK cells within the null lymphocyte population of the spleen. Trophoblast cells appeared to share NK target structures with YAC-1 lymphoma cells, suggesting that a rise in the NK cell level in both pregnancy types may represent a response of the mother to such target structures. Since the density of such moieties was similar for homozygous and heterozygous trophoblasts, a higher NK cell response during allogeneic pregnancy is considered to result indirectly from an alloreactive response of the mother to the paternally encoded antigens on the fetoplacental unit, possibly from a stimulation of interferon producing cells such as macrophages. Nevertheless, such a response appears to be harmless for the allogeneic conceptus.