LIMITING DILUTION ANALYSIS OF THE ALLO-MHC ANTI-PATERNAL CYTOTOXIC T-CELL RESPONSE .1. NORMAL PRIMIGRAVID AND MULTIPAROUS PREGNANCIES

Anti-paternal cytotoxic T lymphocyte precursor frequencies (CTLpF) wer e determined by limiting dilution analysis (LDA) in the peripheral blo od of eight primigravid and seven multiparous women during the three t rimesters of pregnancy. In five of these women the responses to cord b lood lymphocytes (CBL) and paternal lymphocytes were also determined a t the time of delivery and at 6 weeks post delivery. As controls, CTLp F against unrelated third party donors were determined. A wide range o f CTLpF against all three groups of targets was found in both the prim igravid and multiparous women, reflecting the wide range of frequencie s found in random populations. These frequencies remained fairly const ant during and 6 weeks after the pregnancy. Splitwell analysis demonst rated that the responses generated in our culture system were specific to the stimulator. The LDA data conform to single-hit kinetics, indic ating that only cytotoxic T cells were limiting in the assay. Prolifer ative responses of maternal lymphocytes to paternal, cord blood and th ird party MHC antigens also remained unchanged as determined by time-c ourse mixed lymphocyte reactions (MLR). Our data suggest that there is no significant allo-stimulation or suppression of the maternal immune system during normal pregnancy. The mother remains immunocompetent an d is capable of both cytotoxic and proliferative responses to paternal ly-derived fetal MHC antigens. Our findings confirm that in normal pre gnancy the trophoblast, which is devoid of classical MHC antigens, for ms an effective immune barrier which prevents interaction of the mater nal and fetal immune systems.