The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
CD4+CD25+ Regulatory T Cells Can Mediate Suppressor Function in the Absence of Transforming Growth Factor β1 Production and Responsiveness
Open accessAbstract
CD4+CD25+ regulatory T cells inhibit organ-specific autoimmune diseases induced by CD4+CD25−T cells and are potent suppressors of T cell activation in vitro. Their mechanism of suppression remains unknown, but most in vitro studies suggest that it is cell contact–dependent and cytokine independent. The role of TGF-β1 in CD4+CD25+ suppressor function remains unclear. While most studies have failed to reverse suppression with anti–transforming growth factor (TGF)-β1 in vitro, one recent study has reported that CD4+CD25+ T cells express cell surface TGF-β1 and that suppression can be completely abrogated by high concentrations of anti–TGF-β suggesting that cell-associated TGF-β1 was the primary effector of CD4+CD25+-mediated suppression. Here, we have reevaluated the role of TGF-β1 in CD4+CD25+-mediated suppression. Neutralization of TGF-β1 with either monoclonal antibody (mAb) or soluble TGF-βRII-Fc did not reverse in vitro suppression mediated by resting or activated CD4+CD25+ T cells. Responder T cells from Smad3−/− or dominant-negative TGF-β type RII transgenic (DNRIITg) mice, that are both unresponsive to TGF-β1–induced growth arrest, were as susceptible to CD4+CD25+-mediated suppression as T cells from wild-type mice. Furthermore, CD4+CD25+ T cells from neonatal TGF-β1−/− mice were as suppressive as CD4+CD25+ from TGF-β1+/+ mice. Collectively, these results demonstrate that CD4+CD25+ suppressor function can occur independently of TGF-β1.
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Cites
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CD4+CD25+ Immunoregulatory T Cells
McHugh, R. S., Whitters, M. J., Piccirillo, C. A., Young, D. A., Shevach, E. M., Collins, M., & Byrne, M. C. (2002) · Immunity · doi:10.1016/s1074-7613(02)00280-7 · Cited by 1,395
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Cited by
Veldhoen, M., Hocking, R. J., Atkins, C. J., Locksley, R. M., & Stockinger, B. (2006) · Immunity · doi:10.1016/j.immuni.2006.01.001 · Cited by 3,605
Vignali, D. A. A., Collison, L. W., & Workman, C. J. (2008) · Nature Reviews Immunology · doi:10.1038/nri2343 · Cited by 3,463
Sakaguchi, S. (2004) · Annual Review of Immunology · doi:10.1146/annurev.immunol.21.120601.141122 · Cited by 3,306
The PD‐1 pathway in tolerance and autoimmunity
Francisco, L. M., Sage, P. T., & Sharpe, A. H. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00923.x · Cited by 2,300
A function for interleukin 2 in Foxp3-expressing regulatory T cells
Fontenot, J. D., Rasmussen, J. P., Gavin, M. A., & Rudensky, A. Y. (2005) · Nature Immunology · doi:10.1038/ni1263 · Cited by 1,819
Metadata
- Authors
- Piccirillo, C. A., Letterio, J. J., Thornton, A. M., McHugh, R. S., Mamura, M., Mizuhara, H., & Shevach, E. M.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2002-07-15
- Volume
- 196
- Issue
- 2
- Pages
- 237-246
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2168985658
- Cited by
- 594
- References
- 45
- FWCI
- 21.32
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: CD4+CD25+ Regulatory T Cells Can Mediate Suppressor Function in the Absence of Transforming Growth Factor β1 Production and Responsiveness. https://app.cochat.ai/papers/10.1084/jem.20020590
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- Piccirillo, C. A., Letterio, J. J., Thornton, A. M., McHugh, R. S., Mamura, M., Mizuhara, H., & Shevach, E. M. (2002). CD4+CD25+ Regulatory T Cells Can Mediate Suppressor Function in the Absence of Transforming Growth Factor β1 Production and Responsiveness. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.20020590
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