The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Natural and Induced CD4+CD25+ Cells Educate CD4+CD25− Cells to Develop Suppressive Activity: The Role of IL-2, TGF-β, and IL-10
Open accessAbstract
Thymus-derived, natural CD4+CD25+ regulatory T cells can educate peripheral CD4+CD25− cells to develop suppressive activity by poorly understood mechanisms. TGF-β has IL-2-dependent costimulatory effects on alloactivated naive, human CD4+ T cells and induces them ex vivo to become potent contact-dependent, cytokine-independent suppressor cells. In this study, we report that CD4+CD25+ cells are the targets of the costimulatory effects of IL-2 and TGF-β. These cells do not divide, but, instead, greatly increase the numbers of CD4+CD25− cells that become CD25+ cytokine-independent suppressor cells. These CD4+CD25+ regulatory cells, in turn, induce other alloactivated CD4+CD25− cells to become potent suppressor cells by mechanisms that, surprisingly, require both cell contact and TGF-β and IL-10. The suppressive effects of these secondary CD4+CD25+ cells depend upon TGF-β and IL-10. Moreover, both the naive CD4+ cells induced by IL-2 and TGF-β to become suppressor cells, and the subsequent CD4+CD25− cells educated by them to become suppressors express FoxP3. We suggest that the long-term effects of adoptively transferred natural-like CD4+CD25+ regulatory cells induced ex vivo are due to their ability to generate new cytokine-producing CD4+ regulatory T cells in vivo.
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Citations
Cites
Control of Regulatory T Cell Development by the Transcription Factor Foxp3
Hori, S., Nomura, T., & Sakaguchi, S. (2003) · Science · doi:10.1126/science.1079490 · Cited by 8,187
Foxp3 programs the development and function of CD4+CD25+ regulatory T cells
Fontenot, J. D., Gavin, M. A., & Rudensky, A. Y. (2003) · Nature Immunology · doi:10.1038/ni904 · Cited by 7,745
Abe, M., Harpel, J. G., Metz, C. N., Nunes, I., Loskutoff, D. J., & Rifkin, D. B. (1994) · Analytical Biochemistry · doi:10.1006/abio.1994.1042 · Cited by 757
Cited by
Differentiation of Effector CD4 T Cell Populations
Zhu, J., Yamane, H., & Paul, W. E. (2010) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101212 · Cited by 3,452
Regulatory T cells: mechanisms of differentiation and function
Josefowicz, S. Z., Lu, L.-F., & Rudensky, A. Y. (2012) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141623 · Cited by 2,866
Malek, T. R. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090357 · Cited by 1,079
TGF-β1 maintains suppressor function and Foxp3 expression in CD4+CD25+ regulatory T cells
Marie, J. C., Letterio, J. J., Gavin, M., & Rudensky, A. Y. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042276 · Cited by 985
Benson, M. J., Pino-Lagos, K., Rosemblatt, M., & Noelle, R. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070719 · Cited by 847
Metadata
- Authors
- Zheng, S. G., Wang, J. H., Gray, J. D., Soucier, H., & Horwitz, D. A.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-05-01
- Volume
- 172
- Issue
- 9
- Pages
- 5213-5221
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1787048953
- Cited by
- 652
- References
- 3
- FWCI
- 21.35
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Natural and Induced CD4+CD25+ Cells Educate CD4+CD25− Cells to Develop Suppressive Activity: The Role of IL-2, TGF-β, and IL-10. https://app.cochat.ai/papers/10.4049/jimmunol.172.9.5213
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- Zheng, S. G., Wang, J. H., Gray, J. D., Soucier, H., & Horwitz, D. A. (2004). Natural and Induced CD4+CD25+ Cells Educate CD4+CD25− Cells to Develop Suppressive Activity: The Role of IL-2, TGF-β, and IL-10. The Journal of Immunology. https://doi.org/10.4049/jimmunol.172.9.5213
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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