IL-1 beta breaks tolerance through expansion of CD25(+) effector T cells

O'Sullivan, Brendan J., Thomas, Helen E., Pai, Saparna, Santamaria, Pere, Iwakura, Yoichiro, Steptoe, Raymond J., Kay, Thomas W. H. and Thomas, Ranjeny (2006) IL-1 beta breaks tolerance through expansion of CD25(+) effector T cells. Journal of Immunology, 176 12: 7278-7287. doi:10.4049/jimmunol.176.12.7278

Author O'Sullivan, Brendan J.
Thomas, Helen E.
Pai, Saparna
Santamaria, Pere
Iwakura, Yoichiro
Steptoe, Raymond J.
Kay, Thomas W. H.
Thomas, Ranjeny
Title IL-1 beta breaks tolerance through expansion of CD25(+) effector T cells
Journal name Journal of Immunology   Check publisher's open access policy
ISSN 0022-1767
Publication date 2006-06-01
Year available 2006
Sub-type Article (original research)
DOI 10.4049/jimmunol.176.12.7278
Open Access Status Not yet assessed
Volume 176
Issue 12
Start page 7278
End page 7287
Total pages 10
Editor R. Rich
M. Hogan
Place of publication Bethesda
Publisher American Association of Immunologists
Language eng
Subject 320202 Cellular Immunology
730102 Immune system and allergy
Abstract IL-1 is a key proinflammatory driver of several autoimmune diseases including juvenile inflammatory arthritis, diseases with mutations in the NALP/cryopyrin complex and Crohn's disease, and is genetically or clinically associated with many others. IL-1 is a pleiotropic proinflammatory cytokine; however the mechanisms by which increased IL-1 signaling promotes autoreactive T cell activity are not clear. Here we show that autoimmune-prone NOD and IL-1 receptor antagonist-deficient C57BL/6 mice both produce high levels of IL-1, which drives autoreactive effector cell expansion. IL-1 beta drives proliferation and cytokine production by CD4(+)CD25(+)FoxP3(-) effector/memory T cells, attenuates CD4(+)CD25(+)FoxP3(+) regulatory T cell function, and allows escape of CD4(+)CD25(-) autoreactive effectors from suppression. Thus, inflammation or constitutive overexpression of IL-1 beta in a genetically predisposed host can promote autoreactive effector T cell expansion and function, which attenuates the ability of regulatory T cells to maintain tolerance to self.
Keyword Immunology
Transcription Factor Foxp3
Nonobese Diabetic Mice
Tnf-alpha Therapy
Dendritic Cells
Cd40 Ligand
Nod Mouse
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 117 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 14 Aug 2007, 02:16:53 EST