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IL-9 production of naive CD4+ T cells depends on IL-2, is synergistically enhanced by a combination of TGF- beta and IL-4, and is inhibited by IFN-gamma.
Abstract
Dense CD4+ T cells isolated from naive mice produce only trace amounts of IL-9 when stimulated by immobilized anti-CD3 in combination with anti-CD28 Abs. In this situation, IL-9 production is significantly stimulated by TGF-beta and further enhanced by the addition of IL-4, which, by itself, has only a minimal influence. IFN-gamma was found to inhibit the enhancing effect of IL-4. However, increasing amounts of IL-4 in the presence of a constant concentration of IFN-gamma could overcome the inhibitory activity of IFN-gamma. The application of CD4+ T cells isolated from IL-2 knockout mice unequivocally revealed that IL-2 is essential for the production of IL-9 by T cells. In addition, the use of T cells from IL-4 knockout mice elucidated that the basic (IL-2 + TGF-beta) mediated IL-9 production is independent of IL-4. Therefore, our results demonstrate that optimal IL-9 production of naive dense CD4+ T cells is positively regulated at different levels: 1) by IL-2, which is essential for IL-9 secretion; 2) followed by TGF-beta, which promotes a considerable increase in IL-9 production above the level induced by IL-2; and 3) finally, by IL-4, which requires the presence of IL-2 and TGF-beta to strongly enhance the production of IL-9. IFN-gamma inhibits the production of IL-9 mainly at the level of IL-4 by neutralizing the effect of this cytokine.
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“reports have described an IL-9-secreting population of T cells27.”
From The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation (2010) · cites this paper as [27]
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Metadata
- Authors
- Schmitt, E., Germann, T., Goedert, S., Hoehn, P., Huels, C., Koelsch, S., Kühn, R., Müller, W., Palm, N., & Rüde, E.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- Institute for Immunology, University of Mainz ,
- University of Cologne (DE)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1994-11-01
- Volume
- 153
- Issue
- 9
- Pages
- 3989-3996
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1532660854
- Cited by
- 299
- References
- 0
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 14 · 2023: 9 · 2022: 12 · 2021: 18 · 2020: 17 · 2019: 11 · 2018: 22 · 2017: 28 · 2016: 29 · 2015: 16 · 2014: 17 · 2013: 16 · 2012: 20
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- 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
- IL-9, naive CD4+ T cells, interleukin-2, TGF-beta, IL-4, interferon-gamma, cytokine synergy, cytokine inhibition, IL-4 knockout mice, T cell activation, anti-CD3/CD28 stimulation
- MeSH terms
- Animals, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Female, Interferon-gamma, Interleukin-2, Male, Mice, Inbred BALB C, CD4-Positive T-Lymphocytes, Interleukin-4, Cytokines, Transforming Growth Factor beta, Interleukin-9, Mice, Knockout, Mice
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