| First Author | Ludwinski MW | Year | 2009 |
| Journal | J Clin Invest | Volume | 119 |
| Issue | 6 | Pages | 1706-13 |
| PubMed ID | 19411758 | Mgi Jnum | J:150453 |
| Mgi Id | MGI:3850791 | Doi | 10.1172/JCI37619 |
| Citation | Ludwinski MW, et al. (2009) Critical roles of Bim in T cell activation and T cell-mediated autoimmune inflammation in mice. J Clin Invest 119(6):1706-13 |
| abstractText | Bim, the B cell lymphoma 2-interacting (Bcl2-interacting) mediator, maintains immunological tolerance by deleting autoreactive lymphocytes through apoptosis. We report here that Bim is also, paradoxically, required for the activation of autoreactive T cells. Deletion of Bim in hematopoietic cells rendered mice resistant to autoimmune encephalomyelitis and diabetes, and Bim-deficient T cells had diminished cytokine production. Upon T cell receptor activation, Bim-deficient T cells exhibited severe defects in both calcium release and dephosphorylation of nuclear factor of activated T cells (NFAT) but maintained normal levels of activation of NF-kappaB and MAPKs. The defective calcium signaling in Bim-deficient T cells was associated with a significant increase in the formation of an inhibitory complex containing Bcl2 and the inositol triphosphate receptor (IP3R). Thus, in addition to mediating the death of autoreactive T cells, Bim also controlled T cell activation through the IP3R/calcium/NFAT pathway. These results indicate that a single protein is used to control both the activation and apoptosis of autoreactive T cells and may explain why Bim-deficient mice do not reject their own organs despite lacking thymic negative selection. |
