# Effect of allergic asthma on CD8+ TRM-mediated protection from infection

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $203,200

## Abstract

Individuals suffering from local Th2-type inflammatory diseases, including allergic asthma have increased risk
for serious viral infections, but the cause is unclear. Defense against local infections relies on tissue
resident memory CD8+ T cells (TRM) that reside within peripheral tissues and deliver rapid defense against
pathogens and tumors. Following antigen challenge, CD8+ TRM secrete cytokines that activate innate cells,
induce expression of anti-viral and anti-bacterial genes, and recruit circulating leukocytes for pathogen control.
Given their central role in host protection, we hypothesize that impairment of CD8+ TRM contributes to severe
infection in patients with atopic diseases. Our preliminary data demonstrate that IL-4 uniquely prevents TGF--
induced expression of the adhesion receptors CD49a and CD103 that are required for CD8+ TRM persistence
within peripheral tissues. In parallel, in vivo studies reveal that exposure of CD8+ T cells to IL-4 decreases both
their expression of CD103 as well as their accumulation within skin. Based on these preliminary data, we
propose to extend these studies using a mouse model of allergic asthma to test the novel hypothesis that Th2
cytokines impair lung CD8+ TRM formation, persistence and defense against respiratory infection. Specifically,
we propose to: 1) Determine the impact of a Th2-type microenvironment on lung CD8+ TRM
formation/persistence, as well as on the phenotypic stability of established CD8+ TRM; and 2) Determine the
consequence of IL-4 on lung CD8+ TRM-mediated protective immunity to influenza infection.

## Key facts

- **NIH application ID:** 10353929
- **Project number:** 1R21AI166775-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** SHANNON K BROMLEY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $203,200
- **Award type:** 1
- **Project period:** 2021-09-24 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10353929

## Citation

> US National Institutes of Health, RePORTER application 10353929, Effect of allergic asthma on CD8+ TRM-mediated protection from infection (1R21AI166775-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10353929. Licensed CC0.

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