Extrathymic Development of Vα11 T Cells in Placenta During Pregnancy and Their Possible Physiological Role

The molecular and cellular mechanisms of the feto-maternal immune responses in the placenta in connection with natural abortion remain unclear. In this report we provide evidence that V(alpha11) T cells developed in the placenta may be responsible for the induction of natural abortion. The majority of V(alpha11) TCRs detected during pregnancy showed a consensus motif in the CDR3 region, similar to that of anti-GM3 TCR clones, and were of maternal origin. V(alpha11) TCRs were found in the middle to late stages of gestation due to de novo generation in the placenta, not to migration from the maternal side, as evidenced by the significant increases in the out-of-frame V(alpha11) TCR mRNA and the copy number of circular DNA generated by V(alpha11) gene rearrangements. Furthermore, administration of anti-V(alpha11) Ab to pregnant mice resulted in a significant decrease in the incidence of fetal demise, suggesting that V(alpha11) T cells detected in the placenta develop extrathymically and are involved in natural abortion.