# Impact of Resident Memory CD8 T Cells on Respiratory Virus Transmission

> **NIH NIH F31** · EMORY UNIVERSITY · 2023 · $47,694

## Abstract

PROJECT SUMMARY/ABSTRACT
Intranasal vaccination and respiratory virus infection induces populations of antigen specific B cells and T cells
in mucosal tissues. The resulting memory T cells recognize internal epitopes that are conserved across viral
strains and can provide protection against antigenically novel, potentially pandemic variants. One subset of
memory T cells includes tissue resident memory T cells (TRM) which are poised to provide rapid immune
responses at the site of pathogen entry. Numerous studies using direct intranasal inoculation have demonstrated
that CD8 TRM in the respiratory tract can mediate protection against heterosubtypic influenza strains. However,
the ability of CD8 TRM to limit natural respiratory virus transmission has not been defined. Because murine
adapted influenza viruses do not readily transmit between mice and immunological reagents for ferret and guinea
pig models are limited, studying the immunological mechanisms behind transmission has been significantly
hindered. To bridge this gap in knowledge, we developed a murine model using Sendai virus, a mouse
parainfluenza virus which naturally transmits between mice. Through the use of a Luciferase encoding Sendai
virus, transmission dynamics can be evaluated by in vivo imaging. Our preliminary data demonstrates that
Sendai virus specific CD8 TRM in the respiratory tract limit transmission of Sendai virus to immunized contacts.
We seek to further define the mechanisms underlying this TRM mediated protection against transmission by
evaluating relative contributions of TRM in different anatomical compartments of the respiratory tract. Because
studies have demonstrated that a decline in lung and airway TRM corresponds to a loss of heterosubtypic
immunity, we will evaluate the durability of TRM mediated protection following various vaccination strategies.
Furthermore, we will investigate the TRM antiviral mechanisms that limit transmission with a focus on cytokines
and cytolytic proteins. Understanding cellular immune mechanisms in respiratory virus transmission will impact
future vaccine development designed to prevent respiratory virus outbreaks.

## Key facts

- **NIH application ID:** 10679458
- **Project number:** 1F31HL168914-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** SARAH MICHALETS
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $47,694
- **Award type:** 1
- **Project period:** 2023-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10679458

## Citation

> US National Institutes of Health, RePORTER application 10679458, Impact of Resident Memory CD8 T Cells on Respiratory Virus Transmission (1F31HL168914-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10679458. Licensed CC0.

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