# Mechanisms of resident memory T cell differentiation controlled by antigen recognition in non-lymphoid tissue

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2021 · $382,147

## Abstract

PROJECT SUMMARY/ABSTRACT
Tissue-resident memory CD8+ T cells have now been shown to form and persist in nearly every type of non-
lymphoid tissue. Because these cells are permanently positioned at environmental barrier surfaces such as
the skin, they are believed to be critically important for host defense against pathogens. In fact, tissue-resident
memory T cells are more protective than memory T cells in the circulation against a variety of viral and
bacterial infections. Infection of the skin with Vaccinia virus (VacV) has emerged as an attractive model
system to interrogate the mechanisms that control the formation of highly functional tissue-resident T cell
populations. We have recently demonstrated that local recognition of antigen in the tissue microenvironment is
critical for the formation of tissue-resident memory CD8+ T cells in non-lymphoid tissues. Specifically, we
showed that after effector CD8+ T cells enter the VacV-infected skin, a second antigen encounter causes rapid
expression of CD69 and retention of these T cells in the non-lymphoid tissue. In this proposal, we will now
define the molecular and transcriptional mechanisms that control the formation of tissue-resident memory
CD8+ T cells in the skin microenvironment during a viral infection, as the fundamental immunology that
regulates T cell function and memory differentiation in non-lymphoid tissue remains largely undefined. To
address this question, we will 1) determine how T cell receptor affinity/avidity for antigen shapes the
composition of the tissue-resident memory T cell compartment, 2) determine if a Blimp1/IL-10 signaling axis
controls the formation of tissue-resident memory T cells in the skin, and 3) identify the relevant antigen-
presenting cells (both hematopoietic and non-hematopoietic) that regulate tissue-residency by presenting
peptide and/or other survival factors to CD8+ T cells in the skin during viral infection. The overall goal of this
project will be to define the mechanisms that regulate both the formation and function of tissue-resident
memory T cell populations, which will contribute to our long-term goal of improving vaccine design and
identifying strategies for the treatment of inflammatory disorders of the skin.

## Key facts

- **NIH application ID:** 10223993
- **Project number:** 5R01AI143664-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Jeffrey C. Nolz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,147
- **Award type:** 5
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223993

## Citation

> US National Institutes of Health, RePORTER application 10223993, Mechanisms of resident memory T cell differentiation controlled by antigen recognition in non-lymphoid tissue (5R01AI143664-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10223993. Licensed CC0.

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