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Xu M , Sharma A , Hossain MZ , Wiest DL , Sen JM
Sustained Expression of Pre-TCR Induced beta-Catenin in Post-beta-Selection Thymocytes Blocks T Cell Development
Journal of Immunology. 2009 Jan;182(2) :759-765
PMID: ISI:000262390600004    PMCID: PMC 2701226   
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Pre-TCR and IL-7R signals regulate beta-selection of thymocytes and then must be down-regulated for further development. However, the molecular events that control down-regulation remain unknown. We and others have previously shown that beta-catenin in cooperation with TCF regulates beta-selection. In this paper, we demonstrate that beta-catenin expression is stringently regulated by intrathymic signals, it is expressed at the highest levels in the pre-TCR signaled thymocytes, and is down-regulated in post-beta-selection thymocytes. Pre-TCR-induced beta-catenin regulates initial stages of pre-TCR signaling including expression of early growth response (Egr) genes but must be down-regulated to express ROR gamma t, which is essential for maturation to the CD4(+)CD8(+) double positive (DP) stage. Sustained expression of beta-catenin results in the generation of IL-7R-, Egr-, and TGF beta-expressing pre-DP thymocytes that are blocked in development. These data are consistent with a model in which post-beta-selection, pre-TCR-induced beta-catenin expression must return to background levels for efficient transition to the DP stage. The Journal of Immunology, 2009, 182: 759-765.
Xu, Mai Sharma, Archna Hossain, M. Zulfiquer Wiest, David L. Sen, Jyoti Misra 49 AMER ASSOC IMMUNOLOGISTS; 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA 393RO