# Tissue-specific adaptions to promote localized T cell memory

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $616,391

## Abstract

SUMMARY
CD8 T cells are a critical component of the immune response to intracellular infections and malignancies given
their ability to directly kill target cells in tissues. After the resolution of an acute infection, a small proportion of
antigen-specific T cells persists as long-lived memory cells and provides protection upon re-infection. Memory
CD8 T cell populations show a spectrum of phenotypic, functional, and recirculation capacities as well as the
potential for secondary memory formation. Memory T cells have traditionally been studied in blood and
secondary lymphoid organs, with central memory cells found recirculating between the blood and lymphoid
tissues and effector memory T cells found in blood and tissues. It is now understood that long-lived, tissue-
resident memory CD8 T cells (TRM) comprise a significant portion of the memory immune response, mediating
host protection at sites of potential reinfection and, in some cases, causing immunopathology associated with
chronic infection and autoimmunity. We find that the transition of immune cells from a itinerant, recirculating
pattern to established residence in a specific tissue is accompanied by significant changes in gene expression
and genome accessibility. These T cell adaptations to the unique tissue environment mediate formation, survival,
and function of TRM populations. The transcriptional repressor Hic1 has recently been identified as a critical
regulator of the small intestine (SI) TRM population generated in response to acute viral infection. These findings
raise many new questions, such as (1) Which cues and cellular interactions regulate these adaptations? (2) How
are transcriptional circuits controlling tissue residency, immune function, and memory potential integrated? And
(3) What are the specific targets of Hic1 and its mechanisms of action? In this proposal, we will address the
underlying mechanisms of Hic1 activity in establishing TRM, its role in the transcriptional network governing SI
residency, and its importance in TRM secondary memory potential. We propose the following: Aim 1: Define the
role of Hic1 in the regulation of TRM differentiation and maintenance and the signals that induce Hic1 expression
in infection; Aim 2: Elucidate the role of Hic1 in the transcriptional network governing CD8 T residency in the
small intestine, and Aim 3: Determine the tissue-specific regulation of TRM fates and the potential for proliferation
and contribution to memory responses. These studies will inform efforts to induce “tissue-tailored” immune
responses to improve vaccine efficacy.

## Key facts

- **NIH application ID:** 10779305
- **Project number:** 1R01AI179952-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Ananda W Goldrath
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $616,391
- **Award type:** 1
- **Project period:** 2023-11-08 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10779305

## Citation

> US National Institutes of Health, RePORTER application 10779305, Tissue-specific adaptions to promote localized T cell memory (1R01AI179952-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10779305. Licensed CC0.

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