# Function of T cells at the Maternal-Fetal Interface

> **NIH NIH R01** · YALE UNIVERSITY · 2024 · $676,815

## Abstract

Project Summary: Over the past five years, the leading cause of death worldwide for children under five has
been complications from preterm birth (PTB) (<37 weeks’ gestation). In 2016, almost ten percent of all infants
born in the United States were delivered prematurely, and by 2018 the United States was reported to have the
most adverse outcomes during childbirth in the developed world. Collectively, PTB is estimated to cost 14 billion
dollars annually. Historically, PTB has been challenging to study as the underlying causes are poorly understood,
and there is a lack of physiologically relevant animal models. Progress in understanding the drivers of PTB has
been further stalled by limited access to human tissue for research purposes, as specimens from preterm
deliveries usually require pathological evaluation. Though elusive in mechanism, the placenta is an ideal target
for uncovering triggers of PTB as placental pathologies are observed in many cases. One such pathology is the
presence of inflammatory lesions. While inflammation is elevated during both healthy term and preterm labor,
the literature strongly suggests that differential inflammatory pathways are active in preterm deliveries, and
inflammation may overall be increased compared to term births. Our recently published work was the first to
document the contribution of immune cells within the placental villi (PV) to intraamniotic inflammation in non-
human primates and specifically uncovered that PV T cells are active and inflammatory in this model. In
agreement with these findings, our preliminary data show that T cells with memory phenotypes are present in
the PV in healthy pregnancy and can elicit inflammatory responses when stimulated with antigens from the
uterine environment. Furthermore, preliminary transcriptional data from our group revealed that T cells from
preterm PV transcribe more activation markers than term PV counterparts and correlatively preterm PV have
greater placental destruction indicated by apoptosis of trophoblast cells. We, therefore, hypothesized that failed
restriction of antigen presentation to PV T cells leads to PV T cell overactivation, increased cytokine
production, and subsequent destruction of placental architecture resulting in PTB. This proposal will use
multi-omic analysis coupled with in vitro functional assays on preterm and term placentas to uncover unique PV
T cells: populations, functional capacity, transcriptional machinery, and downstream responses on trophoblasts
in preterm birth. We propose: (1) Perform comparative functional analyses of PV T cells in preterm and
term pregnancies, including anatomic localization, activation state, and TCR repertoire profiles in Aim 1.
(2) Evaluate the consequences of PV T cell activation on placental trophoblast health and function in Aim
2. Our repository of cryopreserved PV samples and ongoing collection of new specimens, expertise in placental
biology and mucosal immunology, and a multidisciplinary team...

## Key facts

- **NIH application ID:** 10756444
- **Project number:** 5R01AI171980-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Liza Konnikova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $676,815
- **Award type:** 5
- **Project period:** 2022-01-25 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10756444

## Citation

> US National Institutes of Health, RePORTER application 10756444, Function of T cells at the Maternal-Fetal Interface (5R01AI171980-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10756444. Licensed CC0.

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