Distinct Effects of T-bet in T H 1 Lineage Commitment and IFN-γ Production in CD4 and CD8 T Cells
Abstract
T-bet is a member of the T-box family of transcription factors that appears to regulate lineage commitment in CD4 T helper (TH) lymphocytes in part by activating the hallmark TH1 cytokine, interferon-gamma (IFN-gamma). IFN-gamma is also produced by natural killer (NK) cells and most prominently by CD8 cytotoxic T cells, and is vital for the control of microbial pathogens. Although T-bet is expressed in all these cell types, it is required for control of IFN-gamma production in CD4 and NK cells, but not in CD8 cells. This difference is also apparent in the function of these cell subsets. Thus, the regulation of a single cytokine, IFN-gamma, is controlled by distinct transcriptional mechanisms within the T cell lineage.
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STAT signals are involved in induction of subset-specific transcription factors: T-bet for Th1; GATA3 for Th2; RORγt for Th17.
“STAT signals have been shown to be involved in the induction of subset-specific transcription factors: T-box expressed in T-cells (T-bet) for Th1; GATA-binding protein-3 (GATA3) for Th2; and retinoic acid receptor-related orphan receptor γt (RORγt) for Th17 cells [12–15].”
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- Authors
- Szabo, S. J., Sullivan, B. M., Stemmann, C., Satoskar, A. R., Sleckman, B. P., & Glimcher, L. H.
- Affiliations
- Harvard University (US)
- The Ohio State University (US)
- Washington University in St. Louis (US)
- Corresponding author
- Glimcher, Laurie H.
- Venue
- Science
- Published
- 2002-01-11
- Volume
- 295
- Issue
- 5553
- Pages
- 338-342
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2128475635
- Cited by
- 1,172
- References
- 0
- Citations by year
- 2026: 7 · 2025: 22 · 2024: 21 · 2023: 28 · 2022: 24 · 2021: 30 · 2020: 36 · 2019: 28 · 2018: 36 · 2017: 42 · 2016: 41 · 2015: 42 · 2014: 66 · 2013: 64 · 2012: 69
- FWCI
- 26.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- T-bet, interferon-gamma, CD4+ T cells, CD8+ T cells, natural killer cells, transcription factors, cytokine regulation, T cell differentiation, cytotoxic T lymphocytes
- MeSH terms
- T-bet Transcription Factor, Animals, Cell Differentiation, Cell Line, Cytotoxicity, Immunologic, Immunoglobulin G, Immunization, Interferon-gamma, Killer Cells, Natural, Mice, Inbred BALB C, Mice, Inbred C57BL, T-Lymphocytes, Cytotoxic, Transcription Factors, CD4-Positive T-Lymphocytes, Interleukin-4, Interleukin-5, Leishmaniasis, Cutaneous, Leishmania major, Gene Targeting, Th1 Cells, Cell Lineage, T-Box Domain Proteins, Mice
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