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-2K^b 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 (~ 3-fold) 10 days post coitus when the GK transgene was inherited from the father. A smaller (~ 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 para- 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.