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The biological effects of progesterone are mediated by a 34-kDa protein named the progesterone-induced blocking factor (PIBF). PIBF, synthesized by lymphocytes of healthy pregnant women in the presence of progesterone, inhibits arachidonic acid release as well as NK activity, and modifies the cytokine balance. Within the cell the full-length PIBF is associated with the centrosome, while secretion of shorter forms is induced by activation of the cell. PIBF induces nuclear translocation of STAT6 as well as PKC phosphorylation and exerts a negative effect on STAT4 phosphorylation. The concentration of PIBF in pregnancy urine is related to the positive or negative outcome of pregnancy; furthermore, premature pregnancy termination is predictable by lower than normal pregnancy PIBF values. In vivo data suggest the biological importance of the above findings. Treatment of pregnant Balb/c mice with the antiprogesterone RU 486 results in an increased resorption rate, which is associated with the inability of spleen cells to produce PIBF. High resorption rates induced by progesterone receptor block as well as those due to high NK activity are corrected by simultaneous PIBF treatment.

Human decidual NK (dNK) cells differ from their peripheral blood (PB)-NK counterparts. The major subset of PB-NK is CD56dim, CD16+, CD160+ (highly cytolytic), whereas the major subpopulation of dNK is CD56bright, CD16- and CD160- (high cytokine producer). Extravillous cytotrophoblast invading the decidua basalis in early pregnancy expresses the polymorphic HLA-C, and nonpolymorphic HLA-E and HLA-G molecules that can interact with specific HLA class I-dependent dNK receptors, including the immunoglobulin-like KIRs, the lectin-like CD94/NKG2 and the CD160 receptors. There is no clear evidence thus far that dNK cells kill trophoblast cells. Instead they are able to secrete cytokines which are likely to be beneficial for the placental development, maternal uterine spiral arteries remodeling, and the antiviral immune response.