# Tissue resident memory T cells and chronic lung allograft dysfunction

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $715,793

## Abstract

Project Summary
Lung transplantation remains the only definitive treatment for many patients with end stage lung disease.
However, the outcomes after lung transplant are meager when compared to other solid organ transplants, with
a median survival of only 6 years. The major limiting factor to long-term survival after lung transplantation is the
high incidence of chronic lung allograft dysfunction (CLAD), a progressive form of a lung allograft failure
associated with high morbidity and mortality affecting half of all transplant recipients by 5 years. Episodes of
acute cellular rejection, a T cell mediated allo-immune inflammation of the lung allograft, are associated with
increased risk of CLAD. Our group previously showed that T cells recruited to the lung during acute cellular
rejection persist within the allograft as tissue resident memory T cells (TRM) and that these TRM migrate to the
airways, the site of tissue pathology in CLAD. The focus of this application is to identify whether lung allograft
TRM are alloreactive and how TRM may interact with their local environment to contribute to the development of
CLAD. Importantly, our preliminary data suggests that systemic immune modulators do not impact lung TRM in
the same way that they effect circulating immune cells. This application plans to advance our understanding of
how commonly used immunosuppressants, like alemtuzumab, basiliximab, glucocorticoids, and cyclosporine
impact the phenotype, function, and persistence of lung TRM compared to circulating T cells. Our research aims
include: 1) Identify the alloreactive potential of recipient-derived allograft TRM in lung transplant recipients with
and without CLAD; 2) Establish the role of lung resident myeloid cells in the maintenance of alloreactive recipient-
derived lung TRM; and 3) Determine the impact of systemic and inhaled immune modulators on lung TRM
persistence and function. The results of these investigations explore a mechanism where alloreactive T cells
contribute to CLAD and elucidate how existing immune modulators impact TRM phenotype and function.

## Key facts

- **NIH application ID:** 10891354
- **Project number:** 5R01HL167901-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Mark Eugene Snyder
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $715,793
- **Award type:** 5
- **Project period:** 2023-07-20 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10891354

## Citation

> US National Institutes of Health, RePORTER application 10891354, Tissue resident memory T cells and chronic lung allograft dysfunction (5R01HL167901-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10891354. Licensed CC0.

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