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Immunity. 2004 Aug;21(2):167-77.

Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction.

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  • 1Division of Cell Biology, La Jolla Institute for Allergy and Immunology, San Diego, California 92121, USA.

Abstract

Antigen-specific immunotolerance limits the expansion of self-reactive T cells involved in autoimmune diseases. Here, we show that the E3 ubiquitin ligase Cbl-b is upregulated in T cells after tolerizing signals. Loss of Cbl-b in mice results in impaired induction of T cell tolerance both in vitro and in vivo. Importantly, rechallenge of Cbl-b mutant mice with the tolerizing antigen results in massive lethality. Moreover, ablation of Cbl-b resulted in exacerbated autoimmunity. Mechanistically, loss of Cbl-b rescues reduced calcium mobilization of anergic T cells, which was attributed to Cbl-b-mediated regulation of PLCgamma-1 phosphorylation. Our results show a critical role for Cbl-b in the regulation of peripheral tolerance and anergy of T cells.

PMID:
15308098
[PubMed - indexed for MEDLINE]
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