# Transcriptional Regulation of CD4+ T Cell Differentiation and Diversified Memory

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $507,907

## Abstract

Project Summary
 T follicular helper (Tfh) cells are essential for germinal center (GC) responses and long-term
humoral immunity. However, the complex regulation that determines the differentiation of Tfh cells, in
particular, the initial CXCR5– versus CXCR5+ CD4+ T cell differentiation, the developmental progression
of CXCR5+CD4+ T cells to become GC-Tfh cells, and the generation of follicular helper-like memory
CD4+ T cells expressing CXCR5, are still not fully understood. Our proposal aims to fill in these
knowledge gaps with long-term goals to identify novel genes/pathways underlying the CD4+ T cell
differentiation.
 In our preliminary studies, we have discovered a novel network engaging various
factors/pathways that fine-tunes CXCR5+ versus CXCR5– CD4+ T cell differentiation and regulates the
generation of cytotoxic CD4+ T cells in the early stage of CD4+ T cell response. By combining RNA-seq,
ATAC-seq, and single cell RNA-seq, our preliminary data also suggest that the PD-1+CXCR5+ pre-Tfh
cells undergo substantial further differentiation to become PD-1hiCXCR5hi GC-Tfh cells. Additionally, we
have generated novel “fate-mapping” reporter mice that will allow us to track the varied CXCR5– and
CXCR5+ memory CD4+ T cells. Thus, in this application, we aim to dissect the molecular underpinning
of the early stage CXCR5+ versus CXCR5– CD4+ T cell differentiation as well as to elucidate the
mechanisms underlying the pre- to GC-Tfh differentiation and the generation of diversified CD4+ T cell
memory.
 Our work will have a profound impact on the field of CD4+ T cell differentiation. The research will
not only shed new light on our understanding of the mechanisms underlying the multiple steps of Tfh
cell differentiation but also establish new model systems for memory CD4+ T cell studies. This proposal
has the potential to provide important knowledge on how to control both the humoral and the cellular
arms of the CD4+ T cell response to aid vaccine development for new pandemic threats and help the
treatment of infectious diseases and autoimmune disorders.

## Key facts

- **NIH application ID:** 10884495
- **Project number:** 5R01AI177467-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Hui Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $507,907
- **Award type:** 5
- **Project period:** 2023-07-07 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884495

## Citation

> US National Institutes of Health, RePORTER application 10884495, Transcriptional Regulation of CD4+ T Cell Differentiation and Diversified Memory (5R01AI177467-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10884495. Licensed CC0.

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