Pregnancy programs epigenetic and transcriptional exhaustion in memory CD8⁺ T cells.

ABSTRACT: Alloreactive memory T cells, unlike naive T cells, fail to be restrained by transplantation tolerance protocols or regulatory T cells, and therefore represent a critical barrier to long-term graft acceptance. Using female mice sensitized by rejection of fully-mismatched paternal skin allografts, we show that subsequent semi-allogeneic pregnancy successfully reprograms memory fetus/graft-specific CD8⁺ T cells (T_FGS) towards hypofunction in a manner that is mechanistically distinct from naive T_FGS. Post-partum memory T_FGS were durably hypofunctional, exhibiting enhanced susceptibility to transplantation tolerance induction. Furthermore, multi-omics studies revealed that pregnancy induced extensive phenotypic and transcriptional modifications in mem

SUBMITTER: Pollard J 

PROVIDER: S-EPMC10104270 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature