Tissue-resident CD8+ T memory cells with unique properties are present in human decidua during early pregnancy.

Abstract

Resident memory T (TRM ) cells reside in the uterus during pregnancy may play an important role in balancing maternal-fetal tolerance with anti-infectious immunity. Although CD8+ TRM and decidual CD8+ T cells have been extensively characterized, the properties of decidual CD8+ TRM (dTRM ) cells remain poorly defined. We investigated the heterogeneity, phenotypes, and functions of dTRM cells, and compared the proportion of dTRM cells between normal pregnancy and recurrent spontaneous abortion (RSA) using flow cytometry. Moreover, we cocultured peripheral CD8+ T (CD8+ pT) cells with trophoblast, or decidual stomal cells (DSCs) in the presence or absence of anti-TGF-β antibody or TGF-β type I receptor inhibitor to explore the effects of maternal-fetal environment on decidual CD8+ TRM cell formation. We found that CD69+ CD103+ TRM cells were abundant in CD8+ dT cells but not in CD4+ dT cells with effector-memory (EM, CD45RA- CCR7- ) phenotypes. The percentage of dTRM cells from RSA patients was significantly higher than that from normal pregnancy. Furthermore, dTRM cells showed increased expressions of chemokine receptors, T-cell exhaustion-related molecules, and produced more anti-inflammatorycytokines and effectorcytokines upon stimulation. Moreover, DSCs produced a considerable level of TGF-β and upregulated CD103 expression on CD69+ CD8+ pT cells, which can be significantly reversed by blocking TGF-β receptor. Our findings demonstrate that TRM cells with unique properties are present in the decidua during human early pregnancy. They possess an enhanced capacity to produce effector cytokines and regulatory molecules, which might be important in the balance between maternal-fetal immune tolerance and the capacity to aggressively respond to infections.