# Project 1 - Local regulation of T cell differentiation and function in the reproductive mucosa

> **NIH NIH P20** · BROWN UNIVERSITY · 2021 · $377,375

## Abstract

PROJECT SUMMARY
CD8 T cells defend against tumors and intracellular pathogens. The classical immunosurveillance paradigm
assumes that most CD8 T cells survey for infections by constantly circulating through blood, tissues, and lymph.
This view is being significantly revised after the recent discovery that a large fraction of memory CD8 T cells in
barrier mucosal organs do not routinely circulate. This later group of cells, named resident memory T cells (TRM),
have shown to be particularly critical for controlling infections that target mucosal organs like the female
reproductive tract (FRT). As a barrier tissue FRT is a frequent target of number of intractable pathogens including
HIV and Herpes Simplex virus. There is a growing consensus that vaccines against these diseases should strive
to generate both antibody as well as T-cell mediated responses. And as such efforts to increase antiviral T cell
density in reproductive mucosae has been a key driving factor in the field of T cell vaccinology. Success in these
attempts will depend on a complete understanding of mucosal TRM biology. We hypothesize that maintaining
abundant functional TRM in the mucosae is predicated on TRM’s successful adaptation to the local mucosal
environment; a process that is poorly understood. Local tissue-derived factors are thought to be critical regulators
of this process and represent important targets that can be modulated to influence the quantity, quality and
distribution of TRM. We plan to explore two key aspects of mucosal adaptation program of FRT CD8 TRM. Under
the first aim, we will perform transcriptional and epigenetic analysis of T cells at distinct stages as it enters the
FRT and differentiate into mature TRM cells. Our phenotypic characterization has revealed a significant
heterogeneity among the TRM populations and the transcriptional and chromatin landscape analysis at single
cell resolution will allow us to gain deeper insights into the differentiation trajectories of these populations and
molecular regulators that control this process. Under the second aim, we will interrogate molecules that have
been implicated in antiviral CD8 TRM establishment, differentiation and function. Our pilot data indicates
involvement of local sex steroids and transforming growth factor-beta (TGF-b) in FRT TRM differentiation and
function. Understanding the molecular underpinnings of how FRT CD8 TRM differentiation and function are
regulated will reveal critical targets that can be exploited to both improve CD8 T cell quantity and quality in the
reproductive mucosa for vaccination.

## Key facts

- **NIH application ID:** 10271623
- **Project number:** 2P20GM109035-06
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Lalit K Beura
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,375
- **Award type:** 2
- **Project period:** 2016-06-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271623

## Citation

> US National Institutes of Health, RePORTER application 10271623, Project 1 - Local regulation of T cell differentiation and function in the reproductive mucosa (2P20GM109035-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10271623. Licensed CC0.

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