期刊
NATURE IMMUNOLOGY
卷 11, 期 3, 页码 240-U8出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1845
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资金
- Cancer Research Institute
- Pew Charitable Trusts
- National Institutes of Health [AI067545, AI072117]
- Leukemia & Lymphoma Society
- University of California San Diego
E proteins are basic helix-loop-helix transcription factors that regulate many key aspects of lymphocyte development. Thymocytes express multiple E proteins that are thought to provide cooperative and compensatory functions crucial for T cell differentiation. Contrary to that, we report here that the E protein HEB was uniquely required at the CD4(+)CD8(+) double-positive (DP) stage of T cell development. Thymocytes lacking HEB showed impaired survival, failed to make rearrangements of variable-alpha (V-alpha) segments to distal joining-alpha (J(alpha)) segments in the gene encoding the T cell antigen receptor alpha-chain (Tcra) and had a profound, intrinsic block in the development of invariant natural killer T cells (iNKT cells) at their earliest progenitor stage. Thus, our results show that HEB is a specific and essential factor in T cell development and in the generation of the iNKT cell lineage, defining a unique role for HEB in the regulation of lymphocyte maturation.
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