# Tissue Regulatory T Cells in Mucosal Infection

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $549,799

## Abstract

PROJECT SUMMARY/ABSTRACT
Regulatory T cells (Tregs) are a subset of CD4 T cells that are essential for the maintenance of peripheral
tolerance, yet their precise roles during infections remain an active area of investigation. It is well-documented
that following certain infections, Tregs are required to attenuate an overly robust immune response to prevent
collateral damage to self-tissues. However, we have demonstrated that removal of Tregs prior to infection with
Herpes Simplex Virus, type 2 (HSV-2), among other infections, results in delayed clearance of the pathogen,
suggesting that the presence of Tregs can be critical to facilitating an appropriately robust and protective immune
response. These differing results emphasize that the role played by Tregs during infections is context-dependent,
and thus we propose here to focus on the location of the cells and the time post-infection as key factors that
influence the role that Tregs play during mucosal virus infection.
Recent evidence suggests that there exists a distinct subset of Tregs known as tissue Tregs. These cells have
been best-characterized in skin and visceral adipose tissue, where they function to limit inflammation, though it
has been suggested that tissue Tregs in other locations function to prevent autoimmunity, to promote fetal and
graft tolerance, and to impair anti-tumor immune responses in various non-lymphoid tissues. However, despite
the hypothesized role of tissue Tregs in controlling local inflammation to prevent autoimmunity and
immunopathology, local immune responses are routinely and beneficially generated against mucosal infections,
often without excessive tissue destruction at the infection site, and we thus hypothesize that tissue Tregs are
involved in mediating this balance. Additionally, as effector T cell immune memories remain following infection
clearance, we hypothesize that regulatory memory also persists such that these tissue memory T cell
responses can be controlled under both homeostatic conditions as well as upon pathogen re-encounter to
promote local tissue integrity. Therefore, we propose to extend our investigations of the role of Tregs during
mucosal virus infection, now with a focus on the presence and consequences of tissue Tregs on anti-viral
immune responses in mice and humans. Tissue-resident memory T cells have been intensely studied in recent
years, and are now the basis for a promising new vaccine platform, so it is imperative that we understand how
such tissue T cell responses might be regulated in order to support tissue protection in the face of a robust
immune response.

## Key facts

- **NIH application ID:** 9819767
- **Project number:** 5R01AI141435-02
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Jennifer M Lund
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $549,799
- **Award type:** 5
- **Project period:** 2018-11-07 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9819767

## Citation

> US National Institutes of Health, RePORTER application 9819767, Tissue Regulatory T Cells in Mucosal Infection (5R01AI141435-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9819767. Licensed CC0.

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