OX40 costimulation turns off Foxp3+ Tregs.
In: Blood, Jg. 110 (2007-10-01), Heft 7, S. 2501-10
Online
academicJournal
Zugriff:
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-gamma 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.
Titel: |
OX40 costimulation turns off Foxp3+ Tregs.
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Autor/in / Beteiligte Person: | Vu, MD ; Xiao, X ; Gao, W ; Degauque, N ; Chen, M ; Kroemer, A ; Killeen, N ; Ishii, N ; Li, XC |
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Zeitschrift: | Blood, Jg. 110 (2007-10-01), Heft 7, S. 2501-10 |
Veröffentlichung: | 2021- : [New York] : Elsevier ; <i>Original Publication</i>: New York, Grune & Stratton [etc.], 2007 |
Medientyp: | academicJournal |
ISSN: | 0006-4971 (print) |
DOI: | 10.1182/blood-2007-01-070748 |
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