# T Cell Memory to Viruses

> **NIH NIH R01** · EMORY UNIVERSITY · 2024 · $620,693

## Abstract

Chronic viral infections are characterized by a state of T cell dysfunction that is associated with expression of
the PD-1 (programmed cell death 1) inhibitory receptor. A better understanding of the mechanisms that regulate
CD8 T cell responses during chronic viral infection is required to improve immunotherapies that will increase T
cell function and reduce viral load. We have recently identified a novel population of PD-1+ TCF-1+ virus specific
CD8 T cells that act as stem cells to maintain T cell responses during chronic infection of mice with lymphocytic
choriomeningitis virus (LCMV). The studies proposed in the application are focused on understanding how these
virus specific stem-like CD8 T cells are generated and maintained during chronic infection and how this
information can be used to develop rational approaches for optimizing PD-1 directed immunotherapy. In
particular, we ask the following questions: 1) How do these cells maintain their quiescence and the stem-like
state while living in a sea of antigen and getting TCR signals? 2) Are there any novel inhibitory pathways that
are selectively expressed by the stem-like CD8 T cells to maintain their lifestyle during chronic infection? 3) How
can we increase the number of these crucial stem-like CD8 T cells? 4) What are the most optimal PD-1
combination therapies for harnessing the full potential of the stem-like CD8 T cells? The following specific aims
are proposed to address these questions: Specific Aim 1: Determine the role of inhibitory molecules selectively
expressed by virus-specific stem-like CD8 T cells in regulating their quiescence and effector cell output. Specific
Aim 2: Harnessing the potential of PD-1+ stem-like CD8 T cells for optimal immunotherapy in chronic viral
infection.

## Key facts

- **NIH application ID:** 11000069
- **Project number:** 1R01AI186330-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rafi Ahmed
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $620,693
- **Award type:** 1
- **Project period:** 2024-06-12 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11000069

## Citation

> US National Institutes of Health, RePORTER application 11000069, T Cell Memory to Viruses (1R01AI186330-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11000069. Licensed CC0.

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