Maternal and fetal T cells in term pregnancy and preterm labor

Miller, Derek; Gershater, Meyer; Slutsky, Rebecca; Romero, Roberto; Gomez‐Lopez, Nardhy

doi:10.1038/s41423-020-0471-2

Cited by 61 publications

(48 citation statements)

References 255 publications

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“…Preterm neonates also demonstrate decreased antibody titers in response to vaccines and other antigenic stimuli (15). Especially in the premature neonate, evidence suggests that regulatory immune phenomena essential for feto-maternal immune tolerance persist into post-natal life, contributing to the particular vulnerability of this population to impaired immune responses to antigen (15)(16)(17). Despite the attenuation of some adaptive immune responses, the premature infant is also susceptible to exaggerated inflammatory reactions, primarily in the innate system, that contribute to the main inflammatory morbidities of prematurity, including BPD, ROP, NEC, and certain neurologic injury.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum

et al. 2021

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Although most causes of death and morbidity in premature infants are related to immune maladaptation, the premature immune system remains poorly understood. We provide a comprehensive single-cell depiction of the neonatal immune system at birth across the spectrum of viable gestational age (GA), ranging from 25 weeks to term. A mass cytometry immunoassay interrogated all major immune cell subsets, including signaling activity and responsiveness to stimulation. An elastic net model described the relationship between GA and immunome (R=0.85, p=8.75e-14), and unsupervised clustering highlighted previously unrecognized GA-dependent immune dynamics, including decreasing basal MAP-kinase/NFκB signaling in antigen presenting cells; increasing responsiveness of cytotoxic lymphocytes to interferon-α; and decreasing frequency of regulatory and invariant T cells, including NKT-like cells and CD8+CD161+ T cells. Knowledge gained from the analysis of the neonatal immune landscape across GA provides a mechanistic framework to understand the unique susceptibility of preterm infants to both hyper-inflammatory diseases and infections.

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Section: Introductionmentioning

confidence: 99%

Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum

et al. 2021

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“…Both Th1 and Tc17 cells participate in orchestrating proinflammatory responses in health and disease 75,76 . During pregnancy, these T-cell subsets are implicated in the establishment and maintenance of maternal-fetal tolerance [77][78][79] , which play a central role in pregnancy success [80][81][82][83][84][85][86][87][88][89][90] . Hence, these results indicate that SARS-CoV-2 infection alters specific pro-inflammatory T-cell subsets in the maternal circulation, which may compromise the mechanisms of maternal-fetal tolerance.…”

Section: Discussionmentioning

confidence: 99%

“…Concurrent with the cellular immune changes occurring in the periphery of pregnant women with SARS-CoV-2 infection, maternal T-cell responses in the chorioamniotic membranes were also altered, as revealed by our scRNAseq data. Maternal T cells reside at the maternal-fetal interface and their abundance changes as gestation progresses 79 , 91 . This T-cell compartment comprises multiple subsets, including effector/activated T cells, regulatory T cells, and exhausted T cells 78 , 92 , 93 .…”

Section: Discussionmentioning

confidence: 99%

Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2

Garcia‐Flores

Romero

et al. 2021

Preprint

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Pregnant women are a high-risk population for severe/critical COVID-19 and mortality. However, the maternal-fetal immune responses initiated by SARS-CoV-2 infection, and whether this virus is detectable in the placenta, are still under investigation. Herein, we report that SARS-CoV-2 infection during pregnancy primarily induced specific maternal inflammatory responses in the circulation and at the maternal-fetal interface, the latter being governed by T cells and macrophages. SARS-CoV-2 infection during pregnancy was also associated with a cytokine response in the fetal circulation (i.e. umbilical cord blood) without compromising the cellular immune repertoire. Moreover, SARS-CoV-2 infection neither altered fetal cellular immune responses in the placenta nor induced elevated cord blood levels of IgM. Importantly, SARS-CoV-2 was not detected in the placental tissues, nor was the sterility of the placenta compromised by maternal viral infection. This study provides insight into the maternal-fetal immune responses triggered by SARS-CoV-2 and further emphasizes the rarity of placental infection.

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“…Similar to preeclampsia, there is an association with immunological factors also in PTB (75). For instance, maternal T cell infiltration is observed in chronic chorioamnionitis, the most common placental lesion leading to late spontaneous PTB, and increased influx of cytotoxic effector memory cells has been associated with preterm labor and birth (76). Although the overall frequencies of peripheral MAIT cells were unaltered during the course of healthy pregnancy, in HIV-infected pregnant women, and in women with subsequent PTB, MAIT cells subsets were altered with a higher proportion of CD8 + MAIT cells in first trimester in women with PTB compared to term birth (41).…”

Section: Mait Cells In Pregnancy Complicationsmentioning

confidence: 97%

MAIT Cells at the Fetal-Maternal Interface During Pregnancy

et al. 2020

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One of the main functions of the human placenta is to provide a barrier between the fetal and maternal blood circulations, where gas exchange and transfer of nutrients to the developing fetus take place. Despite being a barrier, there is a multitude of crosstalk between maternal immune cells and fetally derived semi-allogeneic trophoblast cells. Therefore, the maternal immune system has a difficult task to both tolerate the fetus but at the same time also defend the mother and the fetus from infections. Mucosal-associated invariant T (MAIT) cells are an increasingly recognized subset of T cells with anti-microbial functions that get activated in the context of non-polymorphic MR1 molecules, but also in response to inflammation. MAIT cells accumulate at term pregnancy in the maternal blood that flows into the intervillous space inside the placenta. Chemotactic factors produced by the placenta may be involved in recruiting and retaining particular immune cell subsets, including MAIT cells. In this Mini-Review, we describe what is known about MAIT cells during pregnancy and discuss the potential biological functions of MAIT cells at the fetal-maternal interface. Since MAIT cells have anti-microbial and tissue-repairing functions, but lack alloantigen reactivity, they could play an important role in protecting the fetus from bacterial infections and maintaining tissue homeostasis without risks of mediating harmful responses toward semi-allogenic fetal tissues.

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Maternal and fetal T cells in term pregnancy and preterm labor

Cited by 61 publications

References 255 publications

Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum

Single-Cell Analysis of the Neonatal Immune System Across the Gestational Age Continuum

Maternal-Fetal Immune Responses in Pregnant Women Infected with SARS-CoV-2

MAIT Cells at the Fetal-Maternal Interface During Pregnancy

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