Proteogenomic and V(D)J Analysis of Human Decidual T Cells Highlights Unique Transcriptional Programming and Clonal Distribution

Abstract

Abstract Immunological tolerance toward the semiallogeneic fetus is one of many maternal adaptations required for a successful pregnancy. T cells are major players of the adaptive immune system and balance tolerance and protection at the maternal–fetal interface; however, their repertoire and subset programming are still poorly understood. Using emerging single-cell RNA sequencing technologies, we simultaneously obtained transcript, limited protein, and receptor repertoire at the single-cell level, from decidual and matched maternal peripheral human T cells. The decidua maintains a tissue-specific distribution of T cell subsets compared with the periphery. We find that decidual T cells maintain a unique transcriptome programming, characterized by restraint of inflammatory pathways by overexpression of negative regulators (DUSP, TNFAIP3, ZFP36) and expression of PD-1, CTLA-4, TIGIT, and LAG3 in some CD8 clusters. Finally, analyzing TCR clonotypes demonstrated decreased diversity in specific decidual T cell populations. Overall, our data demonstrate the power of multiomics analysis in revealing regulation of fetal–maternal immune coexistence.