title: E protein transcription factors are required for the development of CD4(+) lineage T cells.
abstract: The 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.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Mary Elizabeth
authors.initials: ME
authors.lastname: Jones-Mason
authors.forename: Xudong
authors.initials: X
authors.lastname: Zhao
authors.forename: Dietmar
authors.initials: D
authors.lastname: Kappes
authors.forename: Anna
authors.initials: A
authors.lastname: Lasorella
authors.forename: Antonio
authors.initials: A
authors.lastname: Iavarone
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D015704:CD4 Antigens / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D051797:Inhibitor of Differentiation Protein 2 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051796:Inhibitor of Differentiation Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054400:Receptors, CCR7 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015704:CD4 Antigens; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D053699:Interleukin-7 Receptor alpha Subunit; D054400:Receptors, CCR7; C515371:Ccr7 protein, mouse; C497452:Idb2 protein, mouse; C489532:Tcf12 protein, mouse; C075668:Tcf3 protein, mouse; C067679:Idb3 protein, mouse