Cited by 783T-cell and B-cell ImmunologyPsoriasis: Treatment and PathogenesisCytokine Signaling Pathways and Interactions

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T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells

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Lighvani, Andre A., Frucht, David M., Jankovic, Dragana, Yamane, Hidehiro, Aliberti, Julio, Hissong, Bruce D., Nguyen, Bai V., Gadina, Massimo, Sher, Alan, Paul, William E., O'Shea, John J.·2001·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.261570598PMC PMC64996

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Abstract

Differentiation of naive CD4 + T cells into IFN-γ-producing T helper 1 (T H 1) cells is pivotal for protective immune responses against intracellular pathogens. T-bet, a recently discovered member of the T-box transcription factor family, has been reported to play a critical role in this process, promoting IFN-γ production. Although terminal T H 1 differentiation occurs over days, we now show that challenge of mice with a prototypical T H 1-inducing stimulus, Toxoplasma gondii soluble extract, rapidly induced IFN-γ and T-bet; T-bet induction was substantially lower in IFN-γ-deficient mice. Naive T cells expressed little T-bet, but this transcription factor was induced markedly by the combination of IFN-γ and cognate antigen. Human myeloid antigen-presenting cells showed T-bet induction after IFN-γ stimulation alone, and this induction was antagonized by IL-4 and granulocyte/macrophage colony-stimulating factor. Although T-bet was induced rapidly and directly by IFN-γ, it was not induced by IFN-α, lipopolysaccharide, or IL-1, indicating that this action of IFN-γ was specific. Moreover, T-bet induction was dependent on Stat1 but not Stat4. These data argue for a model in which IFN-γ gene regulation involves an autocrine loop, whereby the cytokine regulates a transcription factor that promotes its own production. These findings substantially alter the current view of T-bet in IFN-γ regulation and promotion of cell-mediated immune responses.

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Subsets of intestinal dendritic cells and their role in orally-induced immune responses
Westlund, J. (2013) · Gothenburg University Publications Electronic Archive (Gothenburg University)

Authors: Lighvani, A. A., Frucht, D. M., Jankovic, D., Yamane, H., Aliberti, J., Hissong, B. D., Nguyen, B. V., Gadina, M., Sher, A., Paul, W. E., & O'Shea, J. J.
Affiliations: National Institutes of Health (US)
Lymphocyte Cell Biology Section, Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Immunobiology Section, Laboratory of Parasitic Diseases, and Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; and Cell Biology Laboratory, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
Corresponding author: Frucht, David M.
ORCID: Frucht, David M.
Jankovic, Dragana
Yamane, Hidehiro
Gadina, Massimo
Sher, Alan
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2001-12-18
Volume: 98
Issue: 26
Pages: 15137-15142
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.261570598
PMC: PMC64996
OpenAlex: W2011754426
Cited by: 783
References: 23
Citations by year: 2026: 14 · 2025: 20 · 2024: 17 · 2023: 30 · 2022: 25 · 2021: 25 · 2020: 23 · 2019: 18 · 2018: 26 · 2017: 20 · 2016: 23 · 2015: 24 · 2014: 43 · 2013: 34 · 2012: 40
FWCI: 13.58
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
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: T-bet, interferon-gamma, Toxoplasma gondii, STAT1, autocrine loop, IL-4, GM-CSF, myeloid antigen-presenting cells, naive CD4+ T cells, T-box transcription factor, cell-mediated immunity
MeSH terms: T-bet Transcription Factor, Animals, Antibodies, Monoclonal, Base Sequence, Cell Differentiation, Cells, Cultured, Dendritic Cells, Female, Humans, Interferon-gamma, Macrophages, Mice, Inbred C57BL, Transcription Factors, CD4-Positive T-Lymphocytes, Up-Regulation, DNA Primers, T-Box Domain Proteins, Mice

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T-bet is rapidly induced by interferon-γ in lymphoid and myeloid cells

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