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Updated: Sep 25, 2026

Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets
Published on: April 16, 2015
Cytokines and transcription factors that regulate T helper cell differentiation: new players and new insights
Davide Agnello1, Carla S R Lankford, Jay Bream
1Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Building 10, Room 9N262, 10 Center Drive, MSC 1820, Bethesda, Maryland 20802-1820, USA.
Abstract:
The differentiation of naive CD4+ T cells into subsets of T helper cells is a pivotal process with major implications for host defense and the pathogenesis of immune-mediated diseases. Though the basic paradigm was discovered more than 15 years ago, new discoveries continue to be made that offer fresh insights into the regulation of this process. T helper (TH)1 cells produce interferon (IFN)-gamma, promoting cell-mediated immunity and control of intracellular pathogens. We now know that TH1 differentiation is regulated by transcription factors such as T-bet, Stat1, and Stat4, as well as cytokines such as IL-12, IL-23, IL-27, type I IFNs, and IFN-gamma. In contrast, TH2 cells produce IL-4, which promotes allergic responses and is important in host defense against helminths. The transcription factors Stat6, GATA-3, c-Maf, NFATs, and the cytokine IL-4 promote TH2 differentiation. These key regulators of TH differentiation are the subject of this review.
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