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Deenick, E.K.* ; Po, L.* ; Chapatte, L.* ; Murakami, K.* ; Lu, Y.C.* ; Elford, A.R.* ; Saibil, S.D.* ; Ruland, J. ; Gerondakis, S.* ; Mak, T.W.* ; Ohashi, P.S.*

c-Rel phenocopies PKCθ but not Bcl-10 in regulating CD8⁺ T-cell activation versus tolerance.

Eur. J. Immunol. 40, 867-877 (2010)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Anergy; CD8+ T cells; NF-kB pathway; Tolerance
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Quellenangaben Band: 40, Heft: 3, Seiten: 867-877 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed