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Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells
Chen X.2; Baumel M.1; Mannel D.N.1; Howard O.M.Z.3; Oppenheim J.J.3
2007-07-01
Source PublicationJournal of Immunology
ISSN00221767
Volume179Issue:1Pages:154-161
AbstractAlthough TNF is a major proinflammatory cytokine, increasing evidence indicates that TNF also has immunosuppressive feedback effects. We have demonstrated in this study that, in both resting and activated states, mouse peripheral CD4CD25 T regulatory cells (Tregs) expressed remarkably higher surface levels of TNFR2 than CD4CD25 T effector cells (Teffs). In cocultures of Tregs and Teffs, inhibition of proliferation of Teffs by Tregs was initially transiently abrogated by exposure to TNF, but longer exposure to TNF restored suppressive effects. Cytokine production by Teffs remained continually suppressed by Tregs. The profound anergy of Tregs in response to TCR stimulation was overcome by TNF, which expanded the Treg population. Furthermore, in synergy with IL-2, TNF expanded Tregs even more markedly up-regulated expression of CD25 and FoxP3 and phosphorylation of STAT5, and enhanced the suppressive activity of Tregs. Unlike TNF, IL-1β and IL-6 did not up-regulate FoxP3-expressing Tregs. Furthermore, the number of Tregs increased in wild-type mice, but not in TNFR2 mice following sublethal cecal ligation and puncture. Depletion of Tregs significantly decreased mortality following cecal ligation and puncture. Thus, the stimulatory effect of TNF on Tregs resembles the reported costimulatory effects of TNF on Teffs, but is even more pronounced because of the higher expression of TNFR2 by Tregs. Moreover, our study suggests that the slower response of Tregs than Teffs to TNF results in delayed immunosuppressive feedback effects.
DOI10.4049/jimmunol.179.1.154
URLView the original
Language英語
Citation statistics
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.National Cancer Institute at Frederick
2.SAIC-Frederick
3.Universitat Regensburg
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GB/T 7714
Chen X.,Baumel M.,Mannel D.N.,et al. Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells[J]. Journal of Immunology,2007,179(1):154-161.
APA Chen X.,Baumel M.,Mannel D.N.,Howard O.M.Z.,&Oppenheim J.J..(2007).Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells.Journal of Immunology,179(1),154-161.
MLA Chen X.,et al."Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4+CD25+ T regulatory cells".Journal of Immunology 179.1(2007):154-161.
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