# Adrenergic Control of Memory T Cells by Circadian Rhythms

> **NIH NIH R21** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $202,500

## Abstract

PROJECT SUMMARY – ABSTRACT
This application seeks to understand how circadian rhythms control immune function through signals delivered
by the sympathetic nervous system. Circadian rhythms are biological clocks that are entrained by light/dark
cycles, and in mammals, those rhythms are synchronized systemically throughout the body via signals delivered
by sympathetic and parasympathetic neurons. Our recent studies uncovered an unexpected role for the
sympathetic nervous system in the generation and development of memory CD8+ T cells in response to a virus
infection. CD8+ T cells lacking the b2-adrenergic receptor (ADRB2) expanded and developed into primary
effectors during early responses to virus, but their progeny failed to develop into a stable pool of memory cells.
This defect correlated with a profound dysregulation of genes involved in circadian rhythms during the early
stages of T cell priming. This proposal will test the hypothesis that the signaling through the ADRB2 in CD8+
T cells regulates circadian rhythm genes, and that those genes are required for memory T cell development.
Aim 1 will measure the periodic oscillations of core clock gene and protein expression in the absence or
presence of the Adrb2 in CD8+ T cells. Aim 2 will determine the intrinsic role of clock genes in regulating
memory CD8+ T cell development. This proposal tests a very straight-forward hypothesis, which if supported,
will be the first demonstration that immunologic memory is controlled by the sympathetic nervous system
through circadian rhythms. The implications of such a discovery will have a far-reaching impact on infectious
diseases, vaccination, and cancer immunotherapy.

## Key facts

- **NIH application ID:** 9828065
- **Project number:** 5R21AI143248-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** John David FARRAR
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $202,500
- **Award type:** 5
- **Project period:** 2018-11-21 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828065

## Citation

> US National Institutes of Health, RePORTER application 9828065, Adrenergic Control of Memory T Cells by Circadian Rhythms (5R21AI143248-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9828065. Licensed CC0.

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