| First Author | Huang F | Year | 2006 |
| Journal | Immunity | Volume | 25 |
| Issue | 4 | Pages | 571-81 |
| PubMed ID | 17045823 | Mgi Jnum | J:114877 |
| Mgi Id | MGI:3690284 | Doi | 10.1016/j.immuni.2006.08.021 |
| Citation | Huang F, et al. (2006) Establishment of the major compatibility complex-dependent development of CD4+ and CD8+ T cells by the Cbl family proteins. Immunity 25(4):571-81 |
| abstractText | Casitas B cell lymphoma (Cbl) proteins are negative regulators for T cell antigen receptor (TCR) signaling. Their role in thymocyte development remains unclear. Here we show that simultaneous inactivation of c-Cbl and Cbl-b in thymocytes enhanced thymic negative selection and altered the ratio of CD4(+) and CD8(+) T cells. Strikingly, the mutant thymocytes developed into CD4(+)- and CD8(+)-lineage T cells independent of the major histocompatibility complex (MHC), indicating that the CD4(+)- and CD8(+)-lineage development programs are constitutively active in the absence of c-Cbl and Cbl-b. The mutant double-positive (DP) thymocytes exhibited spontaneous hyperactivation of nuclear factor-kappa B (NF-kappaB). Additionally, they failed to downregulate the pre-TCR and pre-TCR signaling. Thus, our data indicate that Cbl proteins play a critical role in establishing the MHC-dependent CD4(+) and CD8(+) T cell development programs. They likely do so by suppressing MHC-independent NF-kappaB activation, possibly through downmodulating pre-TCR signaling in DP thymocytes. |
