UM
TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4-1BB and OX40
Hamano R.1,4; Huang J.2; Yoshimura T.1; Oppenheim J.J.1; Chen X.3
2011-07-01
Source PublicationEuropean Journal of Immunology
ISSN00142980 15214141
Volume41Issue:7Pages:2010-2020
Abstract

TNF is a pleiotropic cytokine with intriguing biphasic pro-inflammatory and anti-inflammatory effects. Our previous studies demonstrated that TNF up-regulated FoxP3 expression and activated and expanded CD4FoxP3 regulatory T cells (Tregs) via TNFR2. Furthermore, TNFR2-expressing Tregs exhibited maximal suppressive activity. In this study, we show that TNF, in concert with IL-2, preferentially up-regulated mRNA and surface expression of TNFR2, 4-1BB and OX40 on Tregs. Agonistic antibodies against 4-1BB and OX40 also induced the proliferation of suppressive Tregs. Thus, TNF amplifies its stimulatory effect on Tregs by inducing TNF receptor superfamily (TNFRSF) members. In addition, administration of neutralizing anti-TNF Ab blocked LPS-induced expansion of splenic Tregs and up-regulation of TNFR2, OX40 and 4-1BB receptors on Tregs in vivo, indicating that the expansion of Tregs expressing these co-stimulatory TNFRSF members in response to LPS is mediated by TNF. Altogether, our novel data indicate that TNF preferentially up-regulates TNFR2 on Tregs, and this is amplified by the stimulation of 4-1BB and OX40, resulting in the optimal activation of Tregs and augmented attenuation of excessive inflammatory responses. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KeywordCo-stimulation Immune Regulation Tnf Tregs
DOI10.1002/eji.201041205
URLView the original
Indexed BySCI
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000293131200022
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Cited Times [WOS]:53   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Laboratory of Molecular Immunoregulation, Cancer Inflammation Program, Center for CancerResearch, NCI-Frederick, Frederick, MD, USA
2.SABiosciences Corporation, AQIAGENCompany, Frederick, MD, USA
3.Basic Science Program, SAIC-Frederick, Inc., NCI-Frederick, Frederick, MD, USA
4.Division of Rheumatology, Department of Internal Medicine, Kanazawa University GraduateSchool of Medicine, Kanazawa, Ishikawa, Japan
Recommended Citation
GB/T 7714
Hamano R.,Huang J.,Yoshimura T.,et al. TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4-1BB and OX40[J]. European Journal of Immunology,2011,41(7):2010-2020.
APA Hamano R.,Huang J.,Yoshimura T.,Oppenheim J.J.,&Chen X..(2011).TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4-1BB and OX40.European Journal of Immunology,41(7),2010-2020.
MLA Hamano R.,et al."TNF optimally activatives regulatory T cells by inducing TNF receptor superfamily members TNFR2, 4-1BB and OX40".European Journal of Immunology 41.7(2011):2010-2020.
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