Abstract
The immune system plays a critical role during pregnancy, but the specific mechanisms and immune cell function needed to support pregnancy remain incompletely understood. Despite decades of research efforts, it is still unclear how the immune system maintains tolerance of fetal-derived tissues, which include most cells of the placenta and of course the fetus itself, without forfeiting the ability to protect against harmful infections. T cells recognize antigen in the context of major histocompatibility complex (MHC) encoded proteins, but classical MHC class I and II expression are diminished in fetal-derived cells. Can T cells present at the maternal–fetal interface (MFI) protect these cells from infection? Here we review what is known in regard to tissue-resident memory T (Trm) cells at the MFI. We mainly focus on how Trm cells can contribute to protection in the context of the unique features of the MFI, such as limited MHC expression as well as the temporary nature of the MFI, that are not found in other tissues.
Highlights
Introduction to Memory T Cell SubsetsCirculating in Human Blood and TissuesBefore a CD4 or CD8 T cell can contribute to pathogen clearance, they must first become activated, which requires three distinct signals: a naïve T cell, expressing a unique T cell receptor (TCR) to a cognate antigen, receives a T cell receptor signal (Signal 1) in the context of a costimulatory signal (Signal 2) and inflammation (Signal 3) [21]
The placental structure at the maternal–fetal interface (MFI) consists of chorionic villi including both anchoring villi, made up of extravillous trophoblasts which invade deep within the decidua, eventually replacing the maternal endothelium and remodeling the spiral arteries, and floating villi, which float freely within the intervillous space (Figure 1B) [19,20]
This priming event occurs in the lymph nodes and requires a professional antigen-presenting cell (APC), such as a dendritic cell, to present antigen in the context of major histocompatibility complex (MHC) class I or II to naïve CD8 and CD4 T cells, respectively [22]
Summary
Human pregnancy has a gestational period of 40 weeks, and the role of the maternal immune system continually adapts as the pregnancy progresses. The maternal endometrium undergoes the process of decidualization, which results in remodeling of the maternal spiral arteries, differentiation of maternal stromal cells from fibroblasts to secretory cells, and influx and alterations of immune cells [4]. This specialized endometrial tissue is known as the decidua, which exists only during pregnancy. The placental structure at the MFI consists of chorionic villi including both anchoring villi, made up of extravillous trophoblasts which invade deep within the decidua, eventually replacing the maternal endothelium and remodeling the spiral arteries, and floating villi, which float freely within the intervillous space (Figure 1B) [19,20]. We will first provide a general overview of the different T cell subsets and their associated functional properties followed by a closer look at how the T cell compartment, tissue-resident T cells, in the MFI changes during pregnancy
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