# Tissue Regulation of T Cell Function

> **NIH NIH P01** · UNIVERSITY OF ROCHESTER · 2021 · $2,420,282

## Abstract

PROJECT SUMMARY/ABSTRACT – OVERALL
 Pathogen infection initiates local inflammation that leads to the influx of innate effector cells and elaboration
of chemokines, cytokines and other soluble mediators. T effector cells entering the infected tissue encounter a
tissue environment that has been differentially altered from the basal state depending on the type of pathogen
and corresponding innate inflammatory response. Effector T cells must migrate through this interstitial space
to locate antigen-presenting cells and infected target cells and receive activation signals for effector function,
pathogen clearance and establishment of tissue memory. Although the framework of these complex
interactions between innate cells, soluble mediators and tissue architecture is established, the ability of effector
T cells to sense and interpret different inflammatory environments and the impact on immune function are
poorly understood. Yet, it is within the infected peripheral tissues that they must execute their effector function
for pathogen clearance. It is also within peripheral tissues where dysregulated inflammation leads to immune
pathology; from autoimmune to cardio-vascular disease. Using innovative tools for in situ modulation and
visualization of immune responses in the skin and lung of the mouse the goal of this Program Project is to
gain insight into the signals that control T cell recruitment, migration and activation in infected or
inflamed tissues of the skin and lung. The previous funding cycle has identified new mechanisms of T cell
recruitment, interstitial migration, and positioning of effector and tissue memory subsets. This proposal builds
on these molecular checkpoints at sites of inflammation to determine how external signals from innate cells
and the tissue microenvironment shape the position and function of effector T cells for protective immunity.
 Project 1. Resolution of neutrophil response for effective T cell functions and tissue repair. Dr Minsoo Kim.
Hypothesis: that neutrophil death is not passive, but rather, that the release of specific factors from dying
neutrophils promotes effective T cell activation and tissue repair.
 Project 2. Spatial optimization of T cell activation at inflamed sites via cytokine/chemokine-dependent
cellular clustering. Dr Deborah Fowell. Hypothesis: that peripheral T cell activation occurs in chemokine-rich
peri-vascular clusters that nucleate and amplify T cell recruitment/activation for efficient pathogen clearance.
 Project 3. Formation, Positioning, Motility, and Function of Tissue Resident Memory CD8+ T cells After
Influenza Infection. Dr David Topham. Hypothesis: specific TRM subsets occupy distinct spatial
microenvironments in the airway that confer functional differences in protection against influenza infection.
 Project 4. Mechanics of T cell migration. Dr Patrick Oakes. Hypothesis: that migration of different immune
cells lies along a single continuum, differing only in relative contributi...

## Key facts

- **NIH application ID:** 10241364
- **Project number:** 5P01AI102851-08
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Deborah J Fowell
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,420,282
- **Award type:** 5
- **Project period:** 2014-06-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241364

## Citation

> US National Institutes of Health, RePORTER application 10241364, Tissue Regulation of T Cell Function (5P01AI102851-08). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10241364. Licensed CC0.

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