# Protective CD4+ T Cells

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2021 · $467,388

## Abstract

Project Summary/Abstract
People lacking CD4+ T cells due to acquired or primary immunodeficiency usually become ill due to infection
with microbes such as Mycobacteria, Salmonella, and Cryptococcus that persist in the phagosomes of
phagocytes. Phagosomal pathogens are normally controlled by IFN-γ-producing Th1 cells in granulomas that
form at the initial site of infection. For unknown reasons, however, the Th1 cells can not eliminate the microbes
from the granulomas. The regulatory mechanisms that allow Th1 cells to control these infections in granulomas
without eliminating them are not understood. This knowledge gap has prevented the development of effective
vaccines for phagosomal pathogens that now afflict billions of people.
The goal of this project is to close this gap by using state of the art cell tracking and mouse genetic techniques
to study how Th1 cells specific for peptides from the prototypical phagosomal pathogen Salmonella enterica
and associated granulomas develop during infection. We will build on our finding that S. enterica infection
drives the formation of two types of Th1 cells expressing different chemokine receptors by testing the idea that
persistent infection and thymic production of new T cells drives a cycle in which one Th1 population generates
the senescent and cytotoxic other one. We will use fluorescent bacteria to determine whether these Th1
populations kill the bacteria in phagocytes or kill the phagocytes that harbor the bacteria. We will also
determine whether these processes occur in macrophage-rich granulomas and what role Th1 cells play in
granuloma formation by manipulating the Th1 cells and granuloma macrophages. The potential payoff from
this project is an understanding of this unusual form of non-sterilizing microbial control that protects
immunocompetent individuals from some of the deadliest pathogens but has been impossible to harness via
vaccination.

## Key facts

- **NIH application ID:** 10112150
- **Project number:** 5R01AI103760-09
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Marc Kevin Jenkins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $467,388
- **Award type:** 5
- **Project period:** 2013-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10112150

## Citation

> US National Institutes of Health, RePORTER application 10112150, Protective CD4+ T Cells (5R01AI103760-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10112150. Licensed CC0.

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