# Longevity and Functionality of CD8+ Tissue-resident Memory T cells in the Intestinal Tract

> **NIH NIH F30** · UNIVERSITY OF MINNESOTA · 2020 · $31,380

## Abstract

Project Summary/Abstract
Acute gastroenteritis, attributable to enteric intracellular pathogens, is a significant cause of morbidity and
mortality, particularly in children and the elderly. By itself, norovirus is accountable for nearly 20% of
worldwide cases and upwards of 200,000 deaths annually. Vaccines may mediate protection against
intracellular pathogens by establishing memory CD8 T cell populations that are permanently situated within
the intestinal tissue parenchyma. This subset of memory T cells, known as tissue-resident memory T cells
(TRM), could mediate rapid clearance of infected cells before the pathogen disseminates and manifests
clinically. Indeed, emerging evidence supports a role for CD8 TRM in local pathogen protection in animal
models of intestinal infection. However, it is unknown whether TRM are a transient population. For rational
vaccine design to successfully exploit CD8 TRM in a clinical context, the longevity of CD8 TRM must be
addressed. Extensive preliminary analysis now indicates that the intestinal TRM population undergoes
exponential decay, in contrast to bloodborne memory T cells which remain stable. Specific Aim 1 will test this
question through a novel PCR-based quantification of intestinal TRM and potentially substantiate preliminary
findings. Additionally, we will evaluate the anatomic origin of long-lived intestinal memory T cells. Specific
Aim 2 will address the extent to which preexisting CD8 TRM cells are displaced by new CD8 TRM cells.
Collectively, these studies will address the long-standing questions of longevity, durability, and functionality
of CD8 TRM cells. The protective capacity of long-lived intestinal TRM will be tested against a physiologically
relevant pathogen. Results will have a direct impact on vaccine strategies to protect against intracellular enteric
pathogens. Tissue-resident memory T cells have largely been understudied with preference given to
bloodborne lymphocyte populations. There is now a growing consensus that the interface between cell-
mediated immunity and the tissue parenchyma warrants renewed focus. In the long-term, the studies outlined
here will have broader implications as to how CD8 TRM cells mediate protective immunity, autoimmune
pathogenesis, hypersensitivity reactions, and tumor control, not only in the intestinal tract, but throughout the
body.

## Key facts

- **NIH application ID:** 9978045
- **Project number:** 5F30DK114942-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Sathi Wijeyesinghe
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,380
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978045

## Citation

> US National Institutes of Health, RePORTER application 9978045, Longevity and Functionality of CD8+ Tissue-resident Memory T cells in the Intestinal Tract (5F30DK114942-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9978045. Licensed CC0.

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