# Tissue Resident Memory T Cells in Chronic Allograft Nephropathy

> **NIH NIH F30** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $51,752

## Abstract

Project Summary/Abstract
Kidney transplantation is a lifesaving treatment for patients with end-stage renal failure. However, the success
of kidney transplantation is hindered by the development of chronic kidney graft rejection. The immunocellular
mechanisms leading to chronic kidney graft rejection remain poorly understood. Recent work has described a
population of memory T cells that can take up residence in non-lymphoid tissues, including the kidney. This
subpopulation, known as tissue resident memory T cells (TRM cells), are distinct from circulating memory T cells
in that they are physically poised for immediate re-activation, rapid cytokine release, and recruitment of other
immune cells. Our lab has demonstrated that TRM cells are present and mostly likely sustain chronic kidney graft
rejection in mice, and we as well as others have identified T cells with a TRM phenotype in human renal and lung
allografts undergoing rejection.
With this emerging evidence that support a role for TRM cells in chronic graft rejection, it remains unknown how
TRM cells survive in the graft. Previous studies of TRM survival are limited to models of acute viral infection at a
barrier surface organ where antigen is cleared. Kidney transplantation represents a unique situation where
antigen is persistent and the kidney is a non-barrier surface organ. This distinction is likely to be of critical
importance, where TRM cells of kidney allografts may have different survival requirements from what is known
from previous work. Together, the experiments could reveal the unique survival requirements of TRM cells in
kidney allografts. This information is clinically important because disruption of alloreactive TRM cells could
possibly extend graft function or even prevent chronic graft rejection. One can envision prophylactic treatment
of patients to prevent alloreactive TRM cells from forming as well as therapeutic treatment of patients to selectively
target alloreactive TRM cells.
Three specific aims are proposed to interrogate the relationship of TRM maintenance and chronic kidney graft
rejection. Aim 1 will investigate the role of antigen and antigen presenting cells in generation and maintenance
of TRM cells. Aim 2 will evaluate the requirement for IL-15 signaling in maintenance of TRM through conditional
deletion of IL-15 signaling. Aim 3 will test whether interfering with TRM maintenance will ameliorate chronic
allograft nephropathy.
In addition to my rigorous research training, my training plan outlines my longitudinal clinical experiences,
coursework, and professional and leadership development activities. Altogether, this proposal will serve as the
framework of my training plan to become an academic physician-scientist by integrating basic science research
with a clinical focus in transplantation.

## Key facts

- **NIH application ID:** 10364720
- **Project number:** 5F30DK124925-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Roger Tieu
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 5
- **Project period:** 2020-04-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364720

## Citation

> US National Institutes of Health, RePORTER application 10364720, Tissue Resident Memory T Cells in Chronic Allograft Nephropathy (5F30DK124925-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10364720. Licensed CC0.

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