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Open Access Green as soon as Postprint is submitted to ZB.
c-Rel phenocopies PKCθ but not Bcl-10 in regulating CD8⁺ T-cell activation versus tolerance.
Eur. J. Immunol. 40, 867-877 (2010)
Elucidating the signaling events that promote T-cell tolerance versus activation provides important insights for manipulating immunity in vivo. Previous studies have suggested that the absence of PKCtheta results in the induction of anergy and that the balance between the induction of the transcription factors NFAT, AP1 and NF-kappaB plays a key role in determining whether T-cell anergy or activation is induced. Here, we examine whether Bcl-10 and specific family members of NF-kappaB act downstream of PKCtheta to alter CD8(+) T-cell activation and/or anergy. We showed that T cells from mice deficient in c-Rel but not NF-kappaB1 (p50) have increased susceptibility to the induction of anergy, similar to T cells from PKCtheta-deficient mice. Surprisingly T cells from Bcl-10-deficient mice showed a strikingly different phenotype to the PKCtheta-deficient T cells, with a severe block in TCR-mediated activation. Furthermore, we have also shown that survival signals downstream of NF-kappaB, are uncoupled from signals that mediate T-cell anergy. These results suggest that c-Rel plays a critical role downstream of PKCtheta in controlling CD8(+) T-cell anergy induction.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Anergy; CD8+ T cells; NF-kB pathway; Tolerance
ISSN (print) / ISBN
0014-2980
e-ISSN
1521-4141
Journal
European Journal of Immunology
Quellenangaben
Volume: 40,
Issue: 3,
Pages: 867-877
Publisher
Wiley
Publishing Place
Hoboken
Reviewing status
Peer reviewed