Defective activation and survival of T cells lacking the Ets-1 transcription factor

• Published in: Nature (London) 1995-10, Vol.377 (6550), p.639-642
• Main Authors: Muthusamy, Natarajan, Barton, Kevin, Leiden, Jeffrey M.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - physiology; Biological and medical sciences; CD3 Complex - biosynthesis; CD4 Antigens - biosynthesis; CD8 Antigens - biosynthesis; Cell Division - physiology; Cell Line; Cell Survival - physiology; Cellular biology; Chimera; DNA-Binding Proteins; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes; Humanities and Social Sciences; Immunobiology; letter; Lymphocyte Activation - physiology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Mice; multidisciplinary; Mutation; Proteins - physiology; Proto-Oncogene Protein c-ets-1; Proto-Oncogene Proteins - deficiency; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Proto-Oncogene Proteins c-ets; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; Science; Science (multidisciplinary); Sequence Deletion; Spleen - cytology; Stem Cells; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Transcription Factors - deficiency; Transcription Factors - genetics; Transcription Factors - physiology
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/377639a0

THE Ets-1 proto-oncogene 1 is a member of the Ets family of eukaryotic transcription factors 2á¤-7 . Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals 4,5,8,9 . Ets-1 is preferentially expressed at high levels in B and T cells of adult mice 10,11 and is regulated during both thymocyte development 11 and T-cell activation *12, 13 . To study the role of Ets-1 in T-cell development and function we have used the RAG-2 -/- complementation system 14 and murine embryonic stem (ES) cells containing homozygous deletions in the Ets-1 gene ( Ets-1 -/- ). Ets-1 -/- - RAG-2 -/- chimaeric mice displayed markedly decreased numbers of mature thymocytes and peripheral T cells. Ets-1 -/- T cells expressed normal levels of CD3 and T-cell antigen receptor (TCR)-α/β. However, they displayed a severe proliferative defect in response to multiple activational signals and demonstrated increased rates of spontaneous apoptosis in vitro . These findings demonstrate that Ets-1 is required for the normal survival and activation of murine T cells.