Th133 - ScRNA-Seq Profiling of Antigen Specific CD4+ T Cells in Semi-Allogeneic Transplantation and Pregnancy

Abstract Text: In pregnancy, the semi-allogeneic fetus is afforded immunological tolerance despite expression of paternal alloantigens. In contrast, full or semi-allogeneic allograft transplantations without immunosuppression succumb to acute rejection. While many studies have focused on CD8+ T Cells in both transplant and pregnancy models, there is a knowledge gap of CD4+ T cell biology at the single cell level. We performed scRNA sequencing on endogenous, donor-specific CD4+ T cells to compare their fate in tolerance induced by pregnancy or co-stimulation blockade to allogeneic heart grafts. We also compared donor-specific CD4+ T cells from skin and heart allograft rejection as well as from pregnancy after skin sensitization to model the intersectionality between pregnancy and transplantation. Donor- specific (based on 2W:I-Ab tetramer-binding) CD4+ T cells from spleen and lymph nodes were sorted and sequenced. We defined shared and distinct unbiased clusters, differentially expressed genes, and pregnancy/transplant specific pathways in donor-specific CD4+ T cells elucidating conserved and divergent gene signatures of tolerance, sensitization, and rejection. Specifically, we leverage our transplant and pregnancy models to report novel heterogeneity in follicular and regulatory T Cells at the single cell level.