First Author | Jeon MS | Year | 2004 |
Journal | Immunity | Volume | 21 |
Issue | 2 | Pages | 167-77 |
PubMed ID | 15308098 | Mgi Jnum | J:93595 |
Mgi Id | MGI:3487197 | Doi | 10.1016/j.immuni.2004.07.013 |
Citation | Jeon MS, et al. (2004) Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction. Immunity 21(2):167-77 |
abstractText | 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. |