Decidualization-associated recruitment of cytotoxic memory CD8+T cells to the maternal-fetal interface for immune defense.

Abstract

Decidual CD8⁺T (dCD8⁺T) cells are pivotal in the maintenance of the delicate balance between immune tolerance towards the fetus and immune resistance against pathogens. The endometrium and decidua represent the uterine environments before and during pregnancy, respectively, yet the composition and phenotypic alterations of uterine CD8⁺T cells in these tissues remain unclear. Using flow cytometry and analysis of transcriptome profiles, we demonstrated that human dCD8⁺T and endometrial CD8⁺T (eCD8⁺T) cells exhibited similar T cell differentiation statuses and phenotypes of tissue infiltrating or residency, compared to peripheral CD8⁺T (pCD8⁺T) cells. However, dCD8⁺T cells showed decreased expression of coinhibitory marker (PD-1), chemotaxis marker (CXCR3), and tissue-resident markers (CD69 and CD103), along with increased expression of granzyme B and granulysin, compared to eCD8⁺T cells. In vitro cytotoxicity assays further demonstrated that dCD8⁺T cells had greater effector functions than eCD8⁺T cells. Additionally, both in vitro and in vivo chemotaxis assays confirmed the recruitment of non-resident effector memory T cell subsets to the pregnant decidua, contributing to the dCD8⁺T cell-mediated anti-infection mechanism at the maternal-fetal interface. This work demonstrates dCD8⁺T cells replenished from the circulation retain their cytotoxic capacity, which may serve as an enhanced defense mechanism against infection during pregnancy.