# Regulation of CD4+ T cell responses during chronic viral infection

> **NIH NIH R21** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2020 · $292,500

## Abstract

PROJECT SUMMARY
Immunity to infectious disease and cancer is dependent on a robust T cell response to clear the pathogen or
compromised cells and establish a memory population to protect against future challenge. Understanding T cell
biology including T cell activation, differentiation, and memory formation can thus guide future studies on the
development of novel therapies to augment this response and impact immunological memory. Although studies
demonstrate the contributions of both CD4+ and CD8+ T cells to the effector response and memory formation
with pathogenic infection, many are focused on the CD8+ T cell compartment and fail to appreciate the
contribution(s) of CD4+ T cells. Our studies recently identified PSGL-1 as an inhibitory receptor expressed on T
cells and showed that deletion of PSGL-1 led to reduced exhaustion in both the CD4+ and CD8+ T cell
compartments in the context of chronic virus infection with LCMV clone 13 (Cl13). This is evidenced by the ability
of PSGL-1-deficient mice to clear LCMV Cl13 infection much earlier than their wildtype counterparts. However,
this ability to clear the chronic infection is lost upon CD4+ T cell depletion, demonstrating the importance of this
population in the immune response necessary for the resolution of infection. We also found that CD4+ T cells,
like CD8+ T cells, display greatly enhanced effector responses to acute infection with LCMV Armstrong, with
greater persistence of functional memory cells. The goal of the studies presented in this proposal is to further
elucidate the contribution(s) of CD4+ T cells in both acute and chronic infection and memory generation and to
further understand how PSGL-1-deficiency confers the capability to clear infection. To this end, the contribution
of PSGL-1 deficient CD4+ T cells will be assessed using adoptive transfer of antigen-specific PSGL-1 deficient
CD4+ T cells. As the CD4+ T cells population forms a more heterogenous population that is known to change
with the temporal progression of infection, single-cell sequencing will be used to identify changes in CD4+ T cells.
PSGL-1-deficient mice are capable of clearing LCMV Cl13 which otherwise establishes a chronic infection in
wildtype mice; the mechanism(s) by which this occurs will be interrogated by studying changes in motility with
PSLG-1-deficiency and the impact of antigen load. As PSGL-1 has been demonstrated to affect T cell activation
and function, it represents a therapeutic target for altering T cell differentiation and memory formation; conditional
deletion and antibody mediated modulation of PSGL-1 signaling will be studied in both acute and chronic models
of infection to further elucidate the role PSGL-1 plays in the T cell compartment. The studies presented here
offer a means to understand how modulation of PSGL-1 signaling could augment T cell function and memory
generation and impact on the ability of CD4+T cells to augment CD8+ T cell responses that could be used in
context of infec...

## Key facts

- **NIH application ID:** 10073378
- **Project number:** 1R21AI154916-01
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** Linda Mac Pherson Bradley
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $292,500
- **Award type:** 1
- **Project period:** 2020-06-18 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073378

## Citation

> US National Institutes of Health, RePORTER application 10073378, Regulation of CD4+ T cell responses during chronic viral infection (1R21AI154916-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10073378. Licensed CC0.

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