# T Cell Memory in Organ Transplantation

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $458,556

## Abstract

Abstract
Memory T cells play a key role in allograft rejection. They represent a sizeable proportion of the
alloreactive T cell repertoire and are superior to naive T cells in driving the effector mechanisms
of acute and chronic rejection.
Much of the research on immune memory in transplantation has focused on circulating effector
(TEM) and central (TCM) memory T cells. Recent studies have identified large populations of non-
circulating, resident memory T cells (TRM) that provide local immunity in non-lymphoid tissues
and are phenotypically, transcriptionally, and functionally distinct from TEM and TCM. TRM-
phenotype cells have been identified in human small bowel and lung allografts but their biology
and function in transplantation are poorly understood.
During the past funding period, we established a mouse kidney transplantation model in which
allografts undergo slow, chronic rejection, and monoclonal and polyclonal T cells that infiltrate the
graft can be tracked and interrogated over time. Using this model, we could show that TRM
(defined by their phenotype, transcriptional profile, non-circulatory behavior, and function) form in
the graft and contribute to rejection. This led to the central thesis that TRM are maintained locally
and sustain rejection locally. In this application we propose to investigate how TRM are maintained
in the allograft. In Aim 1, we will investigate the roles of antigen, dendritic cells, and the cytokine
IL-15. In Aim 2, we will investigate the role of a specific transcriptional and post-transcriptional
regulator (Ebp1), identified by single cell transcriptional analysis, that enhances cell proliferation
and survival. In both aims we will study the effects of interrupting TRM maintenance on chronic
rejection. Answering these questions promises to yield novel biological and therapeutic insights
applicable to organ transplant rejection and possibly other diseases such as GVHD and
autoimmunity.

## Key facts

- **NIH application ID:** 10165462
- **Project number:** 5R01AI049466-18
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Fadi G. Lakkis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $458,556
- **Award type:** 5
- **Project period:** 2001-02-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165462

## Citation

> US National Institutes of Health, RePORTER application 10165462, T Cell Memory in Organ Transplantation (5R01AI049466-18). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10165462. Licensed CC0.

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