Symposium 2-2 - Challenges in elucidating the mechanisms of fetal recognition and tolerance by T cells

Abstract

The fetus is a semi-graft expressing paternally derived antigens that are foreign to the mother, however, it is not rejected by the mother because of the establishment of feto-maternal tolerance. Maternal cytotoxic T cells (CTLs) and CD4+ T helper cells (CD4+Tconv) recognize fetal antigens at the T cell receptor (TCR), while regulatory T cells (Treg) suppress immune responses. To investigate the role of antigen-specific Tregs and CTLs in human pregnancy, we analyzed the TCR variations from single T cells from decidua. In normal pregnancies, the number of Tregs with specific TCRs which were presumed to be paternal antigen-specific Tregs increased in a biased manner. In preeclampsia, antigen specific Tregs were decreased. This suggests that induction of antigen-specific immune tolerance by Tregs was inadequate in preeclampsia. Next, to comprehensively search for pathologically relevant molecules in Tregs and CD4+Tconv that could be targets for immunological therapy, we performed single-cell transcriptome analysis of T cells. The results suggest that Th17 among CD4+Tconvs is increased in PE, but the differentiation pathway may be different from that of Tregs. We would like to mention the results of this study and the prospects for immunological approaches to PE therapy.