# Project 4: Thymic and peripheral Aspects of T cell Aging and Rejuvenation

> **NIH NIH P01** · UNIVERSITY OF ARIZONA · 2020 · $322,747

## Abstract

Naïve T cells (TN) are produced in the thymus, but require peripheral mechanisms to maintain their
homeostasis and function. The premise of this project is that, while thymic involution is a proximal cause of
reduced TN numbers with aging, defects in peripheral maintenance mechanisms in secondary lymphoid
organs (SLO) also significantly contribute to immunosenescence. Surprisingly, the nature and the causes of
these defects that impair peripheral TN cell maintenance with aging remain largely unexplored. This project will
test the hypothesis that defects in the peripheral maintenance of naïve T cells in the SLO must be
understood and corrected to achieve lasting immune rejuvenation. This hypothesis is based on our
recently published and preliminary findings that aging leads to disorganization of lymph node (LN) architecture
resulting in a dysfunctional stromal cell compartment, including the fibroblastic reticular cell (FRC) network in
the T cell zone. These defects consequently led to impairment in production and presentation of key cytokines
essential for optimal cell-cell interactions critical for recruitment and maintenance of TN cells.
 In principle, the age-related changes/defects in TN cell maintenance could be due to changes/defects in
TN cells themselves, or the SLO microenvironment or the circulatory factors surrounding TN and SLO .
Therefore, we will examine how aging impairs maintenance of TN cells over the lifespan at the levels of:
newly produced TN cells (SA1), stromal SLO elements (SA2) and the circulatory milieu (SA3). Once the
defects are dissected, we will formulate interventions that improve peripheral T cell maintenance in aged
organisms. These interventions will be tested by Core D, individually or combined with thymic rejuvenation
treatments coming from P1-3, for the ability to improve protective immunity against infection. This project will
also contribute to the generation of the Immune Aging Timeline, that will correlate age-related changes in
thymus, LN and peripheral T cells in mice to those in humans, providing direct preclinical data that pave the
way for human T cell rejuvenation in older adults.

## Key facts

- **NIH application ID:** 10241203
- **Project number:** 3P01AG052359-04S1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** JANKO Z. NIKOLICH
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $322,747
- **Award type:** 3
- **Project period:** 2017-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241203

## Citation

> US National Institutes of Health, RePORTER application 10241203, Project 4: Thymic and peripheral Aspects of T cell Aging and Rejuvenation (3P01AG052359-04S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241203. Licensed CC0.

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