# T cell Memory to Viruses

> **NIH NIH R01** · EMORY UNIVERSITY · 2020 · $561,600

## 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
restore function in exhausted CD8 T cells. We have recently identified a novel population of 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). These stem-like LCMV specific CD8 T cells are found in the lymphoid tissues
where they reside predominantly in the T cell zones along with naïve CD8 T cells. They act as stem cells by
undergoing a slow self-renewal and can also differentiate to give rise to the terminally differentiated CD8 T
cells that are found at the major sites of infection in lymphoid as well as non-lymphoid tissues. Most
importantly, the proliferative burst of T cells that is seen after PD-1 blockade comes almost exclusively from
this stem-like CD8 T cell subset. Our studies have been confirmed and extended by others who have found
similar CD8 T cells in other chronic viral infections of mice and also in chronic infections of non-human
primates and humans. The studies proposed in the application are now 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. The
following specific aims are proposed to achieve these goals: Specific aim 1: To understand how the generation
and maintenance of virus specific stem-like CD8 T cells is regulated during chronic viral infection. Specific aim
2: To develop strategies for enhancing virus specific stem-like CD8 T cells and optimizing PD-1 directed
immunotherapy.

## Key facts

- **NIH application ID:** 9870869
- **Project number:** 5R01AI030048-27
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Rafi Ahmed
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $561,600
- **Award type:** 5
- **Project period:** 1990-07-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870869

## Citation

> US National Institutes of Health, RePORTER application 9870869, T cell Memory to Viruses (5R01AI030048-27). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9870869. Licensed CC0.

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