The expression of a progesterone-induced immunomodulatory protein in pregnancy lymphocytes.

The immunological effects of progesterone are mediated by a protein, named the progesterone-induced blocking factor (PIBF). The PIBF blocks NK activity in vitro and therefore prevents the abortive effect on high NK activity in mice. Increased NK activity has been suggested to play a role in pregnancy termination; thus NK inhibitory effect of the PIBF should contribute to the maintenance of normal gestation. This study was designed to investigate the relationship between n vivo PIBF-producing capacity and in vitro cytotoxic activity of pregnancy lymphocytes, as well as the clinical status or the outcome of pregnancy. Lymphocytes of 168 pregnant women (96 normal pregnancies, 16 showing clinical symptoms of threatened preterm pregnancy termination, 46 recurrent aborters, and 10 women sampled at the onset of spontaneous abortion or preterm delivery) were isolated on Ficoll-Paque gradient. The lymphocytes were tested for reactivity with a PIBF-specific antibody by immunocytochemistry, and simultaneously for cytotoxic activity to human embryonic fibroblast targets. The percentage of PIBF-positive lymphocytes in peripheral blood of healthy pregnant women was significantly higher than in that of women at risk for premature pregnancy termination. In peripheral blood of patients undergoing spontaneous pregnancy termination at the time of sampling, and in those of women showing symptoms of premature pregnancy termination we found lower than normal percentage of PIBF-positive cells. PIBF expression of the lymphocytes showed an inverse correlation with NK activity, and the rate of PIBF positive lymphocytes was related to the outcome of pregnancy. These data suggest a strong relationship between PIBF producing capacity as well as NK activity of the lymphocytes and the success of gestation.