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Updated: Feb 25, 2026

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Memory-phenotype CD4+ T cells spontaneously generated under steady-state conditions exert innate TH1-like effector
Takeshi Kawabe1,2, Dragana Jankovic2, Shuko Kawabe3
1Cytokine Biology Unit, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. takeshi.kawabe@nih.gov asher@niaid.nih.gov rgermain@niaid.nih.gov.
Pathogen-independent memory-phenotype (MP) CD4+ T cells are generated from naive cells without infection. These MP cells provide innate immunity by producing interferon-gamma, enhancing host defense.
Area of Science:
- Immunology
- Cellular Biology
Background:
- CD4+ T cells include naive, pathogen-specific memory, and pathogen-independent memory-phenotype (MP) cells.
- Mechanisms regulating MP cell generation and function are not well understood.
Purpose of the Study:
- To investigate the homeostatic mechanisms and biological functions of MP cells.
- To elucidate the generation and immune role of MP cells.
Main Methods:
- Studied MP cell generation from peripheral naive cells in vitro.
- Analyzed MP cell subpopulations and their cytokine production.
- Assessed MP cell function in a mouse model of *Toxoplasma gondii* infection.
Main Results:
- MP cells are autonomously generated from naive CD4+ T cells independently of infectious stimulation, requiring T cell receptor (TCR) and CD28 signaling.
- A T-bet(hi) subpopulation of MP cells is continuously generated, driven by interleukin-12 (IL-12), and rapidly produces interferon-gamma (IFN-γ) upon IL-12 stimulation.
- These MP cells confer nonspecific resistance against *Toxoplasma gondii* and augment adaptive CD4+ T cell responses.
Conclusions:
- MP cells are continuously generated from naive precursors in a homeostatic manner.
- MP cells possess a novel innate immune function, providing early T helper 1 (TH1)-like protection against pathogens.
- MP cells bridge innate and adaptive immunity, offering broad host defense capabilities.
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