[PDF][PDF] Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction

MS Jeon, A Atfield, K Venuprasad, C Krawczyk… - Immunity, 2004 - cell.com
MS Jeon, A Atfield, K Venuprasad, C Krawczyk, R Sarao, C Elly, C Yang, S Arya…
Immunity, 2004cell.com
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 …
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 PLCγ-1 phosphorylation. Our results show a critical role for Cbl-b in the regulation of peripheral tolerance and anergy of T cells.
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