# Does the senescent environment contribute to age-related changes in T cell function?

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2020 · $205,000

## Abstract

PROJECT SUMMARY
CD4 T cells are critical for generating high quality, robust immune responses to influenza infection. Age-related
changes, however, compromise the ability of CD4 T cells to differentiate into functional subsets resulting in a
multitude of dysregulated responses including delayed viral clearance and prolonged inflammation during
influenza infection. The Haynes laboratory has shown that aged naïve CD4 T cells exhibit numerous intrinsic
defects including significantly reduced proliferation and production of IL-2 in response to antigenic stimulation.
Moreover, the ability of aged influenza-specific CD4 T cells to differentiate into highly functional T follicular
helper (Tfh) and type 1 helper (Th1) cells is also significantly impaired. Apart from T cell intrinsic changes, it is
clear that extrinsic factors in the aged microenvironment are a major contributor to impaired T cell function
during aging. Using an adoptive transfer approach, we have shown that the aged environment significantly
impacts young T cell proliferation, expansion and differentiation. In addition, young CD4 T cells transferred into
aged hosts express higher levels of the regulatory T cell (Treg) associated transcription factor Foxp3 when
compared to those transferred into young hosts. It is therefore critical that we examine factors within the aged
environment that may contribute to functional defects in CD4 T cells.
 One of the hallmarks of aging is the accumulation of senescent cells. In this project, we will explore the
impact of the senescent environment on CD4 T cell function. Cellular senescence refers to the irreversible
growth arrest that occurs when cells experience potentially oncogenic insults. Most importantly, the number of
senescent cells increases with chronological aging as accumulation surpasses the rate of elimination by
phagocytic cells. Factors secreted by senescent cells can have a direct impact on surrounding cells driving
dysfunction and age-related pathologies. Interestingly, many of these factors are cytokines that drive type 2
helper (Th2), memory, and regulatory CD4 T cell differentiation. The impact of senescent cells on immune
cell function in this context has not yet been studied. It has been shown, however, that deletion of these
cells attenuates the progression of many age related-disorders. Thus, the goal of this proposal will be to
examine the effects of senescent cells on CD4 T cell effector functions. Our overall hypothesis is that
senescent cells alter CD4 T cell helper subset differentiation and effector function. Furthermore, we predict that
ablation of senescent cells in aged mice will significantly improve these age-related CD4 T cell decrements and
promote a more robust effector CD4 T helper cell response to influenza infection.

## Key facts

- **NIH application ID:** 9864045
- **Project number:** 5R21AG060707-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Laura Haynes
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $205,000
- **Award type:** 5
- **Project period:** 2019-02-15 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864045

## Citation

> US National Institutes of Health, RePORTER application 9864045, Does the senescent environment contribute to age-related changes in T cell function? (5R21AG060707-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864045. Licensed CC0.

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