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International Immunology Advance Access originally published online on June 4, 2007
International Immunology 2007 19(6):713-718; doi:10.1093/intimm/dxm033
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© The Japanese Society for Immunology. 2007. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

CD27–CD70 interactions sensitise naive CD4+ T cells for IL-12-induced Th1 cell development

Michiel F. van Oosterwijk1,2, Hedi Juwana1,2, Ramon Arens1,2, Kiki Tesselaar1,3, Marinus H. J. van Oers2, Eric Eldering1 and René A. W. van Lier1

1 Department of Experimental Immunology
2 Department of Hematology, Academic Medical Centre, Amsterdam, The Netherlands
3 Present address: Department of Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands

Correspondence to: R. A. W. van Lier; E-mail: r.vanlier{at}amc.uva.nl

Stimulation of CD27, a member of the tumour necrosis factor receptor family, by its ligand CD70 induces expansion of IFN{gamma} secreting CD4+ and CD8+ T cells in vivo. We here analysed the mechanisms through which CD27 mediates this effect. CD27 co-stimulation induced cell division but did not directly instruct naive CD4+ T cells to differentiate into IFN{gamma}-producing Th1 cells. Rather, in concert with signals delivered through the TCR–CD3 complex, CD27 co-stimulation enhanced the Th1-specific transcription factor T-bet and caused up-regulation of the IL-12Rbeta2 chain. Consequently, CD27-costimulated T cells yielded vast numbers of IFN{gamma}-secreting cells in response to IL-12. Additionally, CD27 ligation induced a strong up-regulation of Bcl-xL, but not of related anti-apoptotic molecules. Thus, CD27–CD70 interactions may promote Th1 formation by permitting naive T cells to respond to differentiation signals and by promoting survival of activated effector T cells.

Keywords: CD27, CD70, T cell differentiation, TNF-R family members

Transmitting editor: T. Kipps

Received 19 October 2005, accepted 26 February 2007.


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