# Modeling the development, structure and regulation of T cell memory

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2024 · $487,050

## Abstract

Project Summary
Immunological memory is a defining characteristic of vertebrate immune systems, and is encoded in part by populations of T lymphocytes that respond rapidly and potently to repeat exposures to pathogens. These populations are remarkably diverse in their phenotypes and trafficking patterns, and collectively form an ecosystem that reflects a lifetime's exposure to pathogens and to our environment. Yet a fundamental and pressing problem remains - we have a very limited quantitative grasp of how immunological memory is established and maintained, how new memories to infections are integrated with existing memories, and how and why these wane over time. A detailed understanding of these phenomena would guide the design of vaccines that induce durable immunity, and the development of therapies to revive and sustain T cell responses in the settings of chronic infections and cancer.
The memory encoded by circulating T cells is highly dynamic. It is sculpted by self-renewal, differentiation, loss, and supplementation or competition with newly-recruited cells. Further, in both mice and humans, memory induced by pathogens co-exists with abundant 'natural' memory T cells, which are specific for commensal and environmental antigens but provide cross-protection to new infections; and with regulatory T cells, that limit inappropriate responses. We have very little understanding of how these three populations relate.
In this project we will integrate together a powerful set of modeling and experimental approaches to confront these uncertainties. Specifically, we will develop a structured population modeling (PDE) approach to use with a fate-mapping system that tracks T cell populations throughout their life-histories. We will then combine the fate mapping system with a DNA labeling method and ODE models to define memory T cell dynamics in detail. Together, these approaches will map the development, structure, and rules of replacement of circulating memory T cell subsets in mice. We will also use data from a novel division-reporter mouse strain to model the emergence and long-term dynamics ofT cell memory to influenza infection. Finally, we will combine modeling with fate-mapping and division-reporter mice to understand how regulatory T cells are maintained, and how they impact both natural and influenza-specific memory populations.

## Key facts

- **NIH application ID:** 10888979
- **Project number:** 5R01AI093870-16
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Andrew Yates
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $487,050
- **Award type:** 5
- **Project period:** 2011-03-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10888979

## Citation

> US National Institutes of Health, RePORTER application 10888979, Modeling the development, structure and regulation of T cell memory (5R01AI093870-16). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10888979. Licensed CC0.

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