Expanded cohorts of maternal CD8+ T-cells specific for paternal MHC class I accumulate during pregnancy

A recombinant H-2K(b) transgene, GK, containing the human HLA-G gene promoter is expressed throughout the trophoblast when inherited paternally, Male GK transgenic mice were mated with female T-cell receptor (TCR) transgenic mice to assess the effect of fetal H-2Kb expression on maternal H-2K(b)-specific CD8(+) T-cells during pregnancy. The number of maternal H-2K(b)-specific CD8(+) T-cells in spleen increased significantly (similar to 3-fold) 10 days post coitus when the GK transgene was inherited from the father. A smaller (similar to 2-fold) increase was observed in the spleen of pregnant females mated with C57BL/10 (H-2(b)) males. No increase was observed in mothers mated to syngeneic male mice. In both cases where expanded cohorts of maternal CD8(+) T-cells were observed the amount of surface CD8 and to a lesser extent, TCR molecules was reduced. No change in the amount of surface CD44 or CD45RB was detected when levels were compared with naive T-cells from control virgin female mice. Expanded cohorts of CD8(+) T-cells were also detected in pars-aortic and inguinal lymph nodes draining the uterus but no changes were observed in mesenteric lymph nodes. This study concludes that maternal CD8(+) T-cells are exposed to paternally inherited fetal MHC class I antigens during pregnancy. Moreover, the phenotype of the CD8(+) T-cells in maternal spleen and lymph nodes that drain the uterus is not typical of activated, antigen-experienced T-cells suggesting that contact with fetal H-2K(b) molecules induces a state of functional unresponsiveness. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.