# Cutaneous pathogen-specific tissue resident memory T cells in human aging

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $558,757

## Abstract

Project Summary:
The waning of immunity has a major impact on morbidity and mortality in the aged.
Antigen-specific, acquired, and especially T-cellular is important in host defense against
chronic intracellular pathogens and cancer. Infections with these microbes and skin
cancers with high mutational burdens and neoepitope loads, are disproportionally high
in the elderly. In this application, the investigative team uses an established tetramer
and TCR toolkit for the study of T-cell responses to varicella zoster virus infections
(VZV) in humans to determine the mechanisms of age-related susceptibility to shingles,
and the mechanisms of action of a uniquely successful vaccine that retains efficacy in
the elderly.
 Recently, it has been appreciated that host defense against many localized infections
is mediated by special populations of tissue resident memory cells, abbreviated TRM. As
murine and human studies have advanced, the lineage of TRM, TRM subsets, and the
transcriptional and metabolic signature of TRM in various tissues have begun to come
into focus. TRM are locally mobile, patrol tissue for antigen, and can proliferate upon
antigen re-exposure, yet do not re-enter the blood and are out of reach of blood-based
studies. Notably, studies of human antigen-specific TRM are rare, such that assays of
overall TRM populations may overlook the complexity of TRM.
 Here, we use VZV infection and vaccination as related probes of TRM T-cells across
the age spectrum. Aim 1 focuses on endogenous reactivation of VZV and uses biopsies
of healed shingles and control skin to, for the first time, fully characterize helpful human
virus-specific TRM at the single cell level. Aim 2 uses the new RZV vaccine for shingles
prevention, which retains efficacy even in aged adults, to determine if the vaccine leads
to TRM seeding in the skin, improvement in the pool of homing-committed cells in the
blood, or both. Taken together, these studies will increase our understanding of age-
related changes in vital effector T-cells and strategies that may be useful to overcome
immune senescence.

## Key facts

- **NIH application ID:** 10468080
- **Project number:** 5R01AG064800-04
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** David M Koelle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $558,757
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10468080

## Citation

> US National Institutes of Health, RePORTER application 10468080, Cutaneous pathogen-specific tissue resident memory T cells in human aging (5R01AG064800-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10468080. Licensed CC0.

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