Elevated gamma interferon-producing NK cells, CD45RO memory-like T cells, and CD4 T cells are associated with protection against malaria infection in pregnancy

Previous studies have shown that gamma interferon (IFN-gamma) production in the placenta is associated with protection against placental malaria. However, it remains unknown which IFN-gamma-producing cell subpopulations are involved in this protection and whether the cellular immune components of protection are the same in the peripheral and the placental blood compartments. We investigated cell subpopulations for CD4, CD8, and CD45RO memory-like T cells and CD56(+)/CD3(-) natural killer (NK) cells and for IFN-gamma production by these cells in maternal peripheral and placental intervillous blood in relation to the status of malaria infection in pregnancy. Of 52 human immunodeficiency virus-negative enrolled pregnant women residing in Western Kenya, 20 had placental parasitemia. We found that the percentages of CD45RO memory-like and CD4 T cells were significantly higher in the periphery than in the placenta, while the CD56/CD3(-) NK-cell percentage was higher in the placenta than in the periphery, suggesting differences in immune cell profiles between the two blood compartments. Furthermore, the percentages of peripheral CD45RO memory-like and CD4 T cells were significantly elevated in aparasitemic women compared to levels in the parasitemic group, with aparasitemic multigravid women having the highest percentages of CD45RO memory-like and CD4 T cells. In contrast, at the placental level, IFN-gamma production by innate NK cells was significantly increased in aparasitemic women compared to parasitemic women, regardless of gravidity. These results suggest that the elevated IFN-gamma-producing NK cells in the placenta and CD45RO memory-like and CD4 T cells in peripheral blood may be involved in protection against malaria infection in pregnancy.