Modulation of T-cell CD3-zeta chain expression during normal pregnancy

The objectives of this study were to assess the modulation of T-cell CD3-zeta expression by factor(s) present in sera of pregnant women, to correlate this activity with markers of T-cell function associated with pregnancy, and to identify the presence of a circulating pregnancy-associated factor responsible for the suppression of CD3-zeta chain. The suppression of TcR/CD3-zeta expression on cultured T-lymphocytes (Jurkat cells) by sera and amniotic fluids from pregnant women was examined by Western immunoblots and quantitated by densitometry. This suppression was correlated with the induction of T-cell apoptosis and reduced production of IL-2. The serum component suppressing zeta expression was characterized by ultrafiltration and protease sensitivity. Incubation of Jurkat cells with sera obtained from women in the first trimester produced a slight, but not statistically significant, suppression of zeta expression; however, sera from pregnant women in the second and third trimesters and amniotic fluids significantly suppressed zeta levels in a dose-dependent manner. The loss of zeta chain correlated with both reduced secretion of IL-2 and induction of lymphocyte apoptosis. Fractionation of sera by ultrafiltration demonstrated that the zeta chain suppressive factor was <5 kDa, and its trypsin-sensitivity suggests a proteinaceous moiety. Pregnancy is associated with a progressive suppression of cell-mediated immunity. These suppressed T-cell functions have been linked to Fas/Fas ligand-induced apoptosis and suppression of Th1 cytokines, including IL-2. We demonstrate that these pregnancy-associated events are mimicked by a factor(s) present in patient-derived fluids. Suppression of zeta expression appears to be due to a circulating low-molecular-weight protein that suppresses CD3-zeta in a concentration-dependent manner.