Decidua-accumulated effector-like memory CD8⁺ T cells orchestrate localized antimicrobial defense without compromising fetal tolerance

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Abstract

Deciphering immune privilege at the maternal-fetal interface is essential for understanding how reproductive success and host defense are simultaneously maintained. Decidualization, occurring within the specialized stromal tissue encapsulating the fetus and placenta, shapes local immune adaptation required for healthy pregnancy. Here, we identify a decidua-enriched effector-like memory CD8+ T cell subset marked by CD45RA in humans and CX3CR1 in mice. These cells preferentially accumulate in the decidua, which harbors a CX3CL1-dominant chemokine niche, and disruption of Cx3cr1 or uterine Cx3cl1 impaired their decidual recruitment and tissue localization. Human CD45RA+ and murine CX3CR1+ decidual memory CD8+ T cells shared conserved transcriptional and functional features, including enhanced cytotoxic potential and limited inflammatory cytokine production. Functionally, CX3CL1-mediated CD8+ T cell accumulation improved local control of prenatal Listeria monocytogenes infection and reduced infection-associated fetal loss. In contrast, fetal antigen-specific CD8+ T cell accumulation and fetal resorption occurred independently of uterine CX3CL1. Together, our findings define the maternal-fetal interface as an active immunological gatekeeper, that compartmentalizing CD8+ T cell-mediated antimicrobial adaptive immunity through the conserved CX3CL1-CX3CR1 axis, supporting pathogen-specific defense while preserving fetal tolerance.

Authors

Lu Liu, Xixi Huang, Tingxuan Yin, Xianyang Hu, Hailin Yu, Guohua Zhu, Chunfang Xu, Jiajia Chen, Jiangyuan Du, Hongyan Wang, Qingyu Wu, Wei Zhang, Feng Wang, Huimei Wu, Meirong Du