Expression of co-stimulatory TNFR2 induces resistance of CD4+FoxP3+ conventional T cells to suppression by CD4+FoxP3+T regulatory cells

UM > Institute of Chinese Medical Sciences

Status	已發表Published
	Expression of co-stimulatory TNFR2 induces resistance of CD4+FoxP3+ conventional T cells to suppression by CD4+FoxP3+T regulatory cells
	Chen, X.; Hamano, R.; Subleski, J.; Hurwitz, A.; Howard, O.; Oppenheim, J.
	2010-07-01
Source Publication	Journal of Immunology
ISSN	0022-1767
Pages	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.
Keyword	TNF TGF-BETA GROWTH-FACTOR ACTIVATION INDUCTION REJECTION RECEPTOR IL-2 P75 PROLIFERATION
URL	View the original
Language	英語English
The Source to Article	PB_Publication
PUB ID	34764
Document Type	Journal article
Collection	Institute of Chinese Medical Sciences
Corresponding Author	Chen, X.
Recommended Citation GB/T 7714	Chen, X.,Hamano, R.,Subleski, J.,et al. Expression of co-stimulatory TNFR2 induces resistance of CD4+FoxP3+ conventional T cells to suppression by CD4+FoxP3+T regulatory cells[J]. Journal of Immunology, 2010, 174-182.
APA	Chen, X.., Hamano, R.., Subleski, J.., Hurwitz, A.., Howard, O.., & Oppenheim, J. (2010). Expression of co-stimulatory TNFR2 induces resistance of CD4+FoxP3+ conventional T cells to suppression by CD4+FoxP3+T regulatory cells. Journal of Immunology, 174-182.
MLA	Chen, X.,et al."Expression of co-stimulatory TNFR2 induces resistance of CD4+FoxP3+ conventional T cells to suppression by CD4+FoxP3+T regulatory cells".Journal of Immunology (2010):174-182.

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