# Cellular and molecular programming of lung resident T cell memory

> **NIH NIH R35** · EMORY UNIVERSITY · 2021 · $775,320

## Abstract

PROJECT SUMMARY
Influenza virus is a major health burden worldwide, resulting in billions of dollars in medical costs and up to
600,00 deaths annually. Thus, a major challenge of pulmonary vaccinology is to develop an approach that will
provide long-lasting and durable immunity in the lung. Seasonal influenza infection is driven largely by
antigenic shift to avoid established antibody responses, limiting the efficacy of current influenza vaccinations
designed to generate humoral immunity to the hemagglutinin protein. One approach to this problem is the
development of vaccines designed to promote the generation of influenza-specific, lung-resident T cell
memory. In animal models and human studies, memory T cells have been shown to significantly reduce viral
loads after influenza challenge, leading to faster viral clearance, decreased transmission, and milder or sub-
clinical symptoms. Lung tissue-resident memory T cells (lung TRM) have been found to be critical for this
protective cellular response to influenza, but lung TRM numbers gradually decline over time. Despite thie
importance for pulmonary immunity, we still have only a basic understanding of the cellular and molecular
mechanisms that control their generation and long-term maintenance, nor have we identified the optimal
vaccination strategies to induce durable lung TRM. Furthermore, the influence on unique microenvironments of
the lung interstitium and lung airways on TRM biology is poorly understood. This proposal seeks to develop a
program in lung TRM biology centered on three related themes: (i) investigating the molecular programming of
TRM that enables their generation following infection and vaccination; (ii) defining the cell- and tissue-intrinsic
mechanisms that drive the gradual loss of lung TRM and testing the ability of novel vaccinations strategies to
improve lung TRM longevity; and (iii) determining the transcriptional and epigenetic programming of influenza-
specific lung TRM at the bulk and single cell level using a biorepository of human lung samples. The overall goal
of this project is to understand the mechanisms driving the initial generation and subsequent decline of
influenza-specific TRM from the lung interstitium and airways. The knowledge gained in this study will provide a
deep understanding of the mechanisms that regulate lung TRM biology to better inform future vaccine design
against respiratory pathogens.

## Key facts

- **NIH application ID:** 10115800
- **Project number:** 5R35HL150803-02
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** JACOB E KOHLMEIER
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $775,320
- **Award type:** 5
- **Project period:** 2020-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10115800

## Citation

> US National Institutes of Health, RePORTER application 10115800, Cellular and molecular programming of lung resident T cell memory (5R35HL150803-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10115800. Licensed CC0.

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