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

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2020 · $381,250

## Abstract

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 formation. One of the most critical challenges to developing new immune-based therapies or
vaccines against Plasmodium is understanding how or whether long-lived Plasmodium-specific memory CD4+
T cells develop, function and persist following infection. In this project we have developed powerful new
cellular, genetic and biochemical approaches that enable direct, high-resolution analyses of bona fide
Plasmodium-specific memory CD4+ T cells. These new approaches facilitate our long-term goal to understand
the quantity and quality of Plasmodium-specific memory CD4+ T cell responses. Our goal is addressed by
three specific aims that test: 1) the phenotype, function and numerical stability of Plasmodium-specific effector
and memory CD4+ T cell populations and their impact on protective humoral immunity; 2) how parasite- and
host-specific factors regulate the formation of long-lived memory CD4+ T cell responses; and 3) the effector
mechanisms and pathways that memory CD4+ T cells use to orchestrate long-lived anti-Plasmodium immunity.
Our innovative 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:** 9934100
- **Project number:** 5R01AI125446-06
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Noah Sullivan Butler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,250
- **Award type:** 5
- **Project period:** 2016-06-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934100

## Citation

> US National Institutes of Health, RePORTER application 9934100, Development and function of CD4+ memory T cells during malaria (5R01AI125446-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934100. Licensed CC0.

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