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Independent roles for IL-2 and GATA-3 in stimulating naive CD4+ T cells to generate a Th2-inducing cytokine environment
Open accessAbstract
T cell receptor (TCR) signaling plays an important role in early interleukin (IL)-4 production by naive CD4+ T cells. This "antigen-stimulated" early IL-4 is sufficient for in vitro Th2 differentiation. Here, we provide evidence that early IL-4 production by naive CD4+ T cells stimulated with cognate peptide requires TCR-induced early GATA-3 expression and IL-2 receptor signaling, both of which are controlled by the degree of activation of extracellular signal-regulated kinase (ERK). Stimulation of naive CD4+ T cells from TCR transgenic mice with low concentrations of peptide-induced IL-2-dependent STAT5 phosphorylation, IL-4-independent early GATA-3 expression, and IL-4 production. Neutralization of IL-2 abolished early IL-4 production without affecting early GATA-3 expression. In addition, naive CD4+ T cells from GATA-3 conditional KO mice failed to produce early IL-4 in response to TCR/CD28 stimulation. Stimulation with high concentrations of peptide abrogated early GATA-3 expression and IL-2-dependent STAT5 phosphorylation, and resulted in the failure to produce early IL-4. This high concentration-mediated suppression of early IL-4 production was reversed by blockade of the ERK pathway. A MEK inhibition rescued early GATA-3 expression and responsiveness to IL-2; these cells were now capable of producing early IL-4 and undergoing subsequent Th2 differentiation.
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“In fact, GATA3 expression can also be induced by T cell receptor (TCR) signaling [41] and other pathways, such as Notch [42] and WNT signaling [43].”
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Metadata
- Authors
- Yamane, H., Zhu, J., & Paul, W. E.
- Affiliations
- National Institutes of Health (US)
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2005-09-19
- Volume
- 202
- Issue
- 6
- Pages
- 793-804
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2212937
- OpenAlex
- W2128181270
- Cited by
- 285
- References
- 38
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 10 · 2023: 11 · 2022: 11 · 2021: 15 · 2020: 8 · 2019: 10 · 2018: 13 · 2017: 18 · 2016: 13 · 2015: 18 · 2014: 28 · 2013: 16 · 2012: 19
- FWCI
- 3.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- interleukin-2, GATA3, naive CD4+ T cells, Th2 differentiation, IL-4 production, T cell receptor signaling, ERK signaling, STAT5 phosphorylation, MEK inhibition, CD28 costimulation, TCR transgenic mice, cytokine environment
- MeSH terms
- Animals, Butadienes, Cells, Cultured, Dendritic Cells, DNA-Binding Proteins, Fluoresceins, Interferon-gamma, Interleukin-2, Lymphocyte Activation, Mice, Inbred A, Mice, Inbred C57BL, Mice, Transgenic, Milk Proteins, Nitriles, Peptides, Phosphorylation, RNA, Messenger, Succinimides, CD4-Positive T-Lymphocytes, Trans-Activators, Interleukin-4, Cytokines, Mice, Knockout, Th2 Cells, Coculture Techniques, MAP Kinase Kinase Kinases, STAT5 Transcription Factor, GATA3 Transcription Factor, Mice
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