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Jones-Mason ME , Zhao XD , Kappes D , Lasorella A , Iavarone A , Zhuang Y
E Protein Transcription Factors Are Required for the Development of CD4(+) Lineage T Cells
Immunity. 2012 Mar;36(3) :348-361
AbstractThe double-positive (DP) to single-positive (SP) transition during T cell development is initiated by downregulation of the E protein transcription factors HEB and E2A. Here, we have demonstrated that in addition to regulating the onset of this transition, HEB and E2A also play a separate role in CD4(+) lineage choice. Deletion of HEB and E2A in DP thymocytes specifically blocked the development of CD4(+) lineage T cells. Furthermore, deletion of the E protein inhibitors Id2 and Id3 allowed CD4(+) T cell development but blocked CD8(+) lineage development. Analysis of the CD4(+) lineage transcriptional regulators ThPOK and Gata3 placed HEB and E2A upstream of CD4(+) lineage specification. These studies identify an important role for E proteins in the activation of CD4(+) lineage differentiation as thymocytes undergo the DP to SP transition.
NotesJones-Mason, Mary Elizabeth Zhao, Xudong Kappes, Dietmar Lasorella, Anna Iavarone, Antonio Zhuang, Yuan Nih[r01gm059638] We thank Q.-J. Li and Y.-Y. Lin for critical reading of the manuscript; Y.-W. He for providing OT-II transgenic mice and constructs used to generate the Id2hCD5 allele; R. Bosselut and Y. Xiong for technical advice on Gata3 intracellular staining; A. Singer for providing Cd4 transgenic mice; Q.-J. Li for providing Rag2-/- congenic mice; P. Zhang for assistance with Id3RFP genotyping; Y. Wan and Y. Wang for providing Gata3f/+Cd4cre samples; M. Dai for assistance with genotyping and i.v. injection; I. Belle for assistance with Id2f/fId3f/fCd4cre mice; M. Kondo and M. Krangel for advice and reagents; the Duke University transgenic facility for assistance with generating gene-targeted mice; the Duke Comprehensive Cancer Center Flow Cytometry facility for cell sorting; and the NIH tetramer facility for mouse CD1d tetramers. This work was supported by funding from NIH (R01GM059638) to Y.Z. 44 Cell press Cambridge 915st Nezra r, 1990, cell, v61, p49