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

Nature. 1995 Oct 19;377(6550):639-42. doi: 10.1038/377639a0.

Abstract

The Ets-1 proto-oncogene is a member of the Ets family of eukaryotic transcription factors. Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals. Ets-1 is preferentially expressed at high levels in B and T cells of adult mice and is regulated during both thymocyte development and T-cell activation. To study the role of Ets-1 in T-cell development and function we have used the RAG-2-/- complementation system 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)-alpha/beta. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • CD3 Complex / biosynthesis
  • CD4 Antigens / biosynthesis
  • CD8 Antigens / biosynthesis
  • Cell Division / physiology
  • Cell Line
  • Cell Survival / physiology*
  • Chimera
  • DNA-Binding Proteins*
  • Lymphocyte Activation / physiology*
  • Mice
  • 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
  • Sequence Deletion
  • Spleen / cytology
  • Stem Cells
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*
  • Transcription Factors / deficiency
  • Transcription Factors / genetics
  • Transcription Factors / physiology*

Substances

  • CD3 Complex
  • CD4 Antigens
  • CD8 Antigens
  • DNA-Binding Proteins
  • ETS1 protein, human
  • Ets1 protein, mouse
  • Proteins
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • Transcription Factors
  • V(D)J recombination activating protein 2