# Elucidating a novel respiratory-mammary axis of T cell immunity

> **NIH AI R00** · SEATTLE CHILDREN'S HOSPITAL · 2026 · $248,984

## Abstract

Breastfeeding is associated with immunological benefits that persist beyond infancy, including reduced risk of
respiratory infection. While these benefits are often attributed to immunoglobulins and antimicrobial compounds,
human milk is also rich in T cells whose function is unknown. A central goal of my research career is to elucidate
the protective function of breastmilk T cells against infant respiratory infection. To this end, I propose to
investigate the respiratory-mammary axis of cellular immunity and its role in the establishment, retention, and
response of tissue resident memory T cells (TRM) in the lactating breast. I hypothesize that i) maternal exposure
to respiratory infections results in priming of T cell populations that go on to seed TRM in both the breast and the
respiratory tract and ii) antigen exposure via saliva of the nursing infant drives persistence of TRM in the lactating
breast. I will use samples from a cohort of mother infant pairs, which includes breastmilk cells (BMC), nasal
mucosal cells (NMC), and peripheral blood mononuclear cells (PBMC). In Aim 1, I will investigate whether T cells
resident to the upper respiratory tract and lactating breast are derived from a shared cellular population by
defining the transcriptional and clonal overlap of T cells from BMC and NMC using single cell RNA sequencing
with paired T cell receptor (TCR)αβ sequencing. In Aim 2, I will evaluate the contribution of infant respiratory
infection and coinciding maternal and infant respiratory infection on the frequency and functional state of
breastmilk T cell subsets. To do this, I will enroll mother-infant pairs seeking care at Seattle Children’s Urgent
Care clinics with PCR-confirmed infant SARS-CoV-2 or influenza A. BMC from acute and convalescent
timepoints will be evaluated by high-parameter flow cytometry for T cell immunophenotyping. In Aim 3, I will
interrogate breastmilk antigen-specific TRM responses in the setting of maternal and infant respiratory 

## Key facts

- **NIH application ID:** 11482691
- **Project number:** 4R00AI182458-03
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Blair  Armistead
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** AI
- **Fiscal year:** 2026
- **Award amount:** $248,984
- **Award type:** 4N
- **Project period:** 2024-12-16T00:00:00 → 2028-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11482691

## Citation

> US National Institutes of Health, RePORTER application 11482691, Elucidating a novel respiratory-mammary axis of T cell immunity (4R00AI182458-03). Retrieved via AI Analytics 2026-05-19 from https://api.ai-analytics.org/grant/nih/11482691. Licensed CC0.

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