The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
OX40 costimulation turns off Foxp3+ Tregs
Open accessAbstract
OX40 is a recently identified T-cell costimulatory molecule that belongs to the TNF/TNFR superfamily. OX40 can be expressed by both activated T effector cells and Foxp3+ Tregs. It is well known that OX40 delivers a potent costimulatory signal to T effector cells, but very little is known about the role of OX40 in regulating the suppressor properties of Foxp3+ Tregs and the de novo generation of new inducible Foxp3+ Tregs from T effector cells. In the present study, we found, by using a newly created foxp3gfp knockin model, that OX40 was dispensable for the genesis and suppressor functions of naturally arising CD4+Foxp3+ Tregs, but stimulating OX40 on the Foxp3+ Tregs abrogated their ability to suppress T effector cell proliferation, IFN-γ production, and T effector cell-mediated allograft rejection. OX40 costimulation did not significantly affect proliferation and survival of the naturally arising Foxp3+ Tregs, but profoundly inhibited Foxp3 gene expression. Importantly, OX40 costimulation to T effector cells prevented the induction of new inducible Foxp3+ Tregs from T effector cells. Our study identified OX40 as a key negative regulator of Foxp3+ Tregs and may have important clinical implications in models of transplantation and autoimmunity.
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Cites
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Cited by
Regulatory T cells: mechanisms of differentiation and function
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Molecular mechanism and function of CD40/CD40L engagement in the immune system
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Clinical relevance of host immunity in breast cancer: from TILs to the clinic
Savas, P., Salgado, R., Denkert, C., Sotiriou, C., Darcy, P. K., Smyth, M. J., & Loi, S. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2015.215 · Cited by 890
Depleting tumor-specific Tregs at a single site eradicates disseminated tumors
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Eradication of spontaneous malignancy by local immunotherapy
Sagiv-Barfi, I., Czerwinski, D. K., Levy, S., Alam, I. S., Mayer, A. T., Gambhir, S. S., & Levy, R. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aan4488 · Cited by 361
Metadata
- Authors
- Vu, M. D., Xiao, X., Gao, W., Degauque, N., Chen, M., Kroemer, A., Killeen, N., Ishii, N., & Chang Li, X.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-10-01
- Volume
- 110
- Issue
- 7
- Pages
- 2501-2510
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2137524068
- Cited by
- 428
- References
- 49
- FWCI
- 9.87
- Type
- journal article
- Language
- en
- Open access
- green
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- Vu, M. D., Xiao, X., Gao, W., Degauque, N., Chen, M., Kroemer, A., Killeen, N., Ishii, N., & Chang Li, X. (2007). OX40 costimulation turns off Foxp3+ Tregs. Blood. https://doi.org/10.1182/blood-2007-01-070748
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