# Mechanisms by which trophoblasts recruit T cells to the placental villi during maternal HIV and CMV co-infection

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2020 · $222,755

## Abstract

PROJECT ABSTRACT
An emerging body of evidence suggests there is increased morbidity and mortality among human
immunodeficiency virus (HIV)-exposed uninfected infants (HEUs) compared to infants born to HIV-uninfected
women (HUU). With the HEU child population increasing at >1 million/year, identifying modifiable mechanisms
underlying these disparities is a global health priority. Several studies suggest that during pregnancy
complicated by maternal HIV infection, exposure to co-pathogens induces placental immune activation, which
may alter placental signaling affecting fetal immunity. One such co-infection is human cytomegalovirus
(HCMV). Epidemiologic studies have reported that HCMV co-infection may contribute to HIV disease
progression and increased mortality. We recently identified the presence of CD8+ T cells in placental villi from
pregnant, South African women living with HIV (PWLHIV) and HCMV co-infection, compared to placentae from
HIV-uninfected women who were HCMV positive. We hypothesize that there is recruitment and migration
of maternally-derived HCMV-specific CD8+ T cells from the uterine decidua to placental villi. We posit
that trophoblasts promote migration of antigen-specific CD8+ T cells into the fetal villi compartment,
which further exacerbates the inflammatory cascade and promotes apoptosis of trophoblast cells. In
order to validate our hypothesis, we will enroll pregnant women attending prenatal care in Cape Town, South
Africa, into two groups: 1) HIV/HCMV co-infected pregnant women; and 2) women with HCMV infection only.
We will determine the origin, phenotype and epitope specificity of these infiltrating T cells, as well as examine
the role of trophoblasts in recruiting these T cells into the villous space. The proposed studies will provide a
deeper conceptual understanding of the in vivo effects of maternal HIV/HCMV co-infection during pregnancy
on placental immunity. These studies could facilitate the development of immunomodulatory and antiviral
therapies targeting inflammation and HCMV, respectively, which may improve clinical outcomes in HEU infants
from HIV- and HCMV-coinfected pregnant women.

## Key facts

- **NIH application ID:** 10080877
- **Project number:** 1R21HD103498-01
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Rana Chakraborty
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $222,755
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080877

## Citation

> US National Institutes of Health, RePORTER application 10080877, Mechanisms by which trophoblasts recruit T cells to the placental villi during maternal HIV and CMV co-infection (1R21HD103498-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10080877. Licensed CC0.

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