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Expression of costimulatory TNFR2 induces resistance of CD4+ FoxP3− conventional T cells to suppression by CD4+ FoxP3+ regulatory T cells
Xin Chen1; Ryoko Hamano2,4; Jeffrey J. Subleski3; Arthur A. Hurwitz2; O. M. Zack Howard2; Joost J. Oppenheim2
2010-07
Source PublicationJOURNAL OF IMMUNOLOGY
ISSN0022-1767
Volume185Issue:1Pages:174-182
Abstract

Our previous study showed that TNFR2 is preferentially expressed by CD4+FoxP3+ regulatory T cells (Tregs), and expression of this receptor identified maximally suppressive Tregs. TNFR2 is also expressed by a small fraction of CD4+FoxP3− conventional T cells (Tconvs) in normal mice, and its expression is upregulated by T cell activation. This raises questions about the role of TNFR2 signaling in the function of Tconv cells. In this study, by using FoxP3/gfp knock-in mice, we showed that TNFR2 signaling did not induce FoxP3− CD4 cells to become suppressive. Ki-67, a marker of proliferation, was concomitantly expressed with TNFR2 by CD4 cells, independent of forkhead box P3 expression, in normal mice and Lewis lung carcinoma-bearing mice. TNFR2 is associated with greater suppressive functions when expressed by Tregs and is associated with greater resistance to suppression when expressed by Tconv cells. In mice bearing 4T1 breast tumor or Lewis lung carcinoma, intratumoral Tconv cells expressing elevated levels of TNFR2 acquired the capacity to resist suppression by lymph node-derived Tregs. However, they remained susceptible to inhibition by more suppressive tumor-infiltrating Tregs,which expressed higher levels of TNFR2. Our data indicate that TNFR2 also costimulates Tconv cells. However, intratumoral Tregs expressing more TNFR2 are able to overcome the greater resistance to suppression of intratumoral Tconv cells, resulting in a dominant immunosuppressive tumor environment.

DOI10.4049/jimmunol.0903548
Indexed BySCIE
WOS Research AreaImmunology
WOS SubjectImmunology
WOS IDWOS:000278933800021
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Cited Times [WOS]:77   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorXin Chen
Affiliation1.Basic Science Program, Science Applications International Corporation-Frederick, Inc.
2.Laboratory of Molecular Immunoregulation Cancer Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702
3.Laboratory of Experimental Immunology, Cancer Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702
4.Division of Rheumatology, Kanazawa University, Kanazawa, Ishikawa, Japan
Recommended Citation
GB/T 7714
Xin Chen,Ryoko Hamano,Jeffrey J. Subleski,et al. Expression of costimulatory TNFR2 induces resistance of CD4+ FoxP3− conventional T cells to suppression by CD4+ FoxP3+ regulatory T cells[J]. JOURNAL OF IMMUNOLOGY,2010,185(1):174-182.
APA Xin Chen,Ryoko Hamano,Jeffrey J. Subleski,Arthur A. Hurwitz,O. M. Zack Howard,&Joost J. Oppenheim.(2010).Expression of costimulatory TNFR2 induces resistance of CD4+ FoxP3− conventional T cells to suppression by CD4+ FoxP3+ regulatory T cells.JOURNAL OF IMMUNOLOGY,185(1),174-182.
MLA Xin Chen,et al."Expression of costimulatory TNFR2 induces resistance of CD4+ FoxP3− conventional T cells to suppression by CD4+ FoxP3+ regulatory T cells".JOURNAL OF IMMUNOLOGY 185.1(2010):174-182.
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