# Memory T cell development and survival in T cell responses of older individuals

> **NIH NIH R01** · PALO ALTO VETERANS INSTIT FOR RESEARCH · 2020 · $351,676

## Abstract

PROJECT SUMMARY / ABSTRACT
Older individuals have increased morbidity and mortality from infections. Vaccination holds the promise of a
cost-effective intervention; however, vaccine responses are generally poor in the elderly and at best ameliorate
disease. One major objective of immune aging research therefore is to identify defects in adaptive immune
responses that impair the generation of immune memory and that can be successfully targeted. After
vaccination or infection, antigen-specific T cells follow a typical sequence of events. First, they exponentially
expand and differentiate into effector cells including follicular helper cells that control the activation of B cells
and the generation of antibodies. While most of these effector cells undergo apoptosis, a small subset
constitutes memory T cell precursors that differentiate into long-lived memory cells. We have provided
evidence that reduced survival of effector T cells contributes to defective memory cell generation in older
individuals. We have shown that CD39 identifies effector CD4 T cells that cannot differentiate into long-lived
memory T cells and that generation of CD39+ CD4 T cells is increased in immune responses of older
individuals. CD39 is not only a surrogate marker, but actively contributes to effector cell apoptosis through its
ATP/Dase activity, implicating purinergic signaling in regulating T cell memory generation. Here, we propose to
identify means to interfere with CD39 expression or to target purinergic signaling to improve generation of T
memory cells. Aim 1 will define the gene-regulatory networks that induce CD39 expression in a subset of CD4
T cells after activation and will identify the molecular basis of increased CD39 expression in older individuals.
Aim 2 will examine whether purinergic signaling can be targeted to improve survival of activated CD4 T cell.
While Aims 1 and 2 involve in vitro experiments, Aim 3 will examine the role of CD39 expression and purinergic
signaling on memory T cell generation in vivo in individuals after varicella zoster vaccination.

## Key facts

- **NIH application ID:** 9904524
- **Project number:** 5R01AI129191-04
- **Recipient organization:** PALO ALTO VETERANS INSTIT FOR RESEARCH
- **Principal Investigator:** JORG J GORONZY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $351,676
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9904524

## Citation

> US National Institutes of Health, RePORTER application 9904524, Memory T cell development and survival in T cell responses of older individuals (5R01AI129191-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9904524. Licensed CC0.

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