Related Experiment Video
Updated: Nov 11, 2025
07:12
Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
53.5K
Two sequential activation modules control the differentiation of protective T helper-1 (Th1) cells
Peter D Krueger1, Michael F Goldberg1, Sung-Wook Hong1
1Center for Immunology, Department of Microbiology and Immunology, University of Minnesota Medical School, Minneapolis, MN 55455 USA.
Immunity
|March 27, 2021
Summary
In vivo, both Salmonella and influenza infections generate T follicular helper (Tfh) and poorly differentiated Th1 cells. Phagosomal pathogen infections, like Salmonella, then amplify Th1 cells via IL-12 for enhanced pathogen control.
Area of Science:
- Immunology
- Cellular Biology
- Microbiology
Background:
- CD4+ T helper-1 (Th1) cells producing Interferon-γ (IFN-γ) are crucial for combating intracellular pathogens.
- Existing knowledge of Th1 cell differentiation primarily stems from in vitro studies.
- Understanding in vivo Th1 cell dynamics during infection is essential.
Purpose of the Study:
- To investigate Th1 cell differentiation and function in vivo during microbial infections.
- To compare Th1 cell generation during infection with a phagosomal pathogen (Salmonella enterica) versus a non-phagosomal pathogen (influenza A virus).
- To elucidate the role of Interleukin-12 (IL-12) in Th1 cell amplification and pathogen control.
Main Methods:
- Tracking antigen-specific CD4+ T cells in vivo during Salmonella enterica (Se) and influenza A virus (IAV) infections.
- Analyzing the induction of T follicular helper (Tfh) and Th1 cell populations.
- Assessing the impact of IL-12 signaling on Th1 cell differentiation and expansion.
- Evaluating the functional capacity of differentiated Th1 cells, including IFN-γ production and cytotoxicity.
Main Results:
- Both Se and IAV infections induced Tfh cells and IL-12-independent Th1 cells.
- During Se infection, Th1 cells subsequently outgrew Tfh cells through an IL-12-dependent pathway.
- Se-induced Th1 cells exhibited enhanced IFN-γ production, ZEB2-dependent cytotoxicity, and improved control of Salmonella infection.
- A distinct IL-12-dependent amplification module for Th1 cells was identified during phagosomal pathogen infections.
Conclusions:
- Infections typically induce a Tfh and basic Th1 cell generation module.
- Phagosomal pathogen infections activate a subsequent IL-12-dependent Th1 cell amplification module.
- This amplification module is critical for effective control of intracellular bacterial infections like Salmonella.
Related Concept Videos
01:22T Cell Activation and Clonal Selection
13.9K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
13.9K
01:24B Cell Activation and Differentiation
15.0K
The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
15.0K
01:24T Cell Types and Functions
1.7K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
1.7K
01:23Cells of the Adaptive Immune Response
7.3K
The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
7.3K
01:40Cell-mediated Immune Responses
79.5K
Overview
79.5K
01:20Special Features of Adaptive Immunity
1.7K
The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
The primary cell types involved in adaptive immunity are T cells and B cells. Each type has a unique role in defending the body against pathogens. T cells are responsible for cell-mediated immunity. They identify and eliminate infected cells directly,...
1.7K