# Development and function of CD4+ memory T cells during malaria

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $466,500

## Abstract

PROJECT SUMMARY
Plasmodium infections and the disease malaria remain global health emergencies. Plasmodium parasites
replicate within and cause the destruction of host red blood cells, which triggers inflammation and causes the
symptoms of malarial disease. Parasite-specific antibody responses that develop following infection are critical
for controlling parasite burden and limiting disease severity. CD4+ helper T cells are essential for coordinating
these protective antibody responses. However, sterilizing anti-Plasmodium immunity rarely develops, even
following repeated infection. We hypothesize this is due to deficient Plasmodium-specific effector and memory
CD4+ T cell development and function. One of the most critical challenges to developing new immune-based
therapies or vaccines against Plasmodium is understanding the mechanisms by which long-lived Plasmodium-
specific memory CD4+ T cells develop, function and persist following infection.
 In the continuation of this project, we apply powerful new cellular and molecular genetic approaches that
enable direct, high-resolution analyses of Plasmodium-specific memory CD4+ T cells. These new approaches
facilitate our long-term goal to understand the mechanisms governing the development and function of
Plasmodium-specific memory CD4+ T cell responses. Our goal is addressed by three specific aims that have
evolved to test: 1) how hemozoin, a parasite-derived product of hemoglobin degradation, influences the induction
and maintenance of Plasmodium-specific memory CD4+ T cell populations; 2) how constraints on host cellular
metabolism shape memory CD4+ T cell formation and function; and 3) how specific epigenetic regulators govern
the differentiation and function of CD4+ memory T cells. Our innovative conceptual and technical advances and
mechanistic approaches enable us to establish additional new paradigms for understanding and enhancing
CD4+ T cell-dependent anti-Plasmodium immunity. Understanding immune memory formation following
Plasmodium infection will enable us to identify and develop new immune-based strategies to limit Plasmodium
pathogenesis and disease burden.

## Key facts

- **NIH application ID:** 10783024
- **Project number:** 5R01AI125446-08
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Noah Sullivan Butler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $466,500
- **Award type:** 5
- **Project period:** 2016-06-15 → 2028-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10783024

## Citation

> US National Institutes of Health, RePORTER application 10783024, Development and function of CD4+ memory T cells during malaria (5R01AI125446-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10783024. Licensed CC0.

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