Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47.
The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis. Here, we provide in vitro and in vivo evidence demonstrating that E47 activity regulates double-positive thymocyte maturation. In the absence of E47 activity, positive selection of both major histocompatibility complex (MHC) class I- and class II-restricted T cell receptors (TCRs) is perturbed. Additionally, development of CD8 lineage T cells in an MHC class I-restricted TCR transgenic background is sensitive to the dosage of E47. Mice deficient for E47 display an increase in production of mature CD4 and CD8 lineage T cells. Furthermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id3, promotes the in vitro differentiation of an immature T cell line. These results demonstrate that E2A functions as a regulator of thymocyte positive selection.
Bain
G
G
Department of Biology, University of California, San Diego, La Jolla, California 92093, USA.
Quong
M W
MW
Soloff
R S
RS
Hedrick
S M
SM
Murre
C
C
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D018628:Gene Dosage; D018257:Helix-Loop-Helix Motifs; D008213:Lymphocyte Activation; D016399:Lymphoma, T-Cell / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000172:deficiency / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051820:TCF Transcription Factors; C544913:Tcf7l1 protein, mouse; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; D001613:beta 2-Microglobulin