SUPPRESSED CELL-MEDIATED-IMMUNITY AND MONOCYTE AND NATURAL-KILLER-CELL ACTIVITY FOLLOWING ALLOGENEIC IMMUNIZATION OF WOMEN WITH SPONTANEOUSRECURRENT ABORTION

Spontaneous recurrent abortion (SRA) has been treated by means of immu nization with paternal or third-party white blood cells, yet the immun ological basis for SRA and for the role of immunization protocols in p regnancy outcome remains controversial. To elucidate this question, ni ne women with SRA were immunized with paternal mononuclear cells and s tudied before and 2 weeks after immunization. Seven women who became p regnant gave birth to live newborns. Secretion of the T helper 1 cytok ines IL-2 and interferon-gamma by patients' mononuclear cells decrease d, while production of IL-10 increased. The levels of natural killer a nd lymphokine-activated killer cell mediated cytotoxicity were markedl y decreased. Monocyte functions such as secretion of IL-1 alpha, tumor necrosis factor alpha, IL-6, and cytotoxic activity decreased concurr ently with elevations in IL-10 and transforming growth factor beta sec retion. Production of IL-12, a pivotal regulatory cytokine, decreased. Furthermore, B7/1 expression on patients' mononuclear cells was downr egulated. This resulted in a decrease in monocyte costimulatory activi ty of purified T cells with soluble anti-CD3, paralleled by a decline in allogeneic proliferative responses. These results suggest that the improved pregnancy success rate in women with SRA following immunizati on may be partly related to suppression of cell-mediated immunity and monocyte and natural killer cell activity.