CD3 epsilon-mediated signals rescue the development of CD4+CD8+ thymocytes in RAG-2-/- mice in the absence of TCR beta chain expression.

  • Shinkai Y
  • Alt F
  • 15

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Abstract

Recent studies have shown that TCR beta chain expression can effect the differentiation of CD4-CD8- double-negative (DN) thymocytes to CD4+CD8+ double-positive (DP) thymocytes. The TCR beta chain is expressed on the surface of DP thymocytes in association with CD3 gamma, delta and epsilon chains, suggesting a potential role for CD3 components in this signaling process. We now report detection of a very low level of surface expression of CD3 epsilon on adult DN RAG-2-/- thymocytes. This surface CD3 epsilon was associated with CD3 gamma and delta chains, as detected by anti-CD3 epsilon immunoprecipitation analyses. Significantly, injection of anti-CD3 epsilon mAb into RAG-2-/- mice led to the accumulation of an IL-2R alpha- CD2+ DP cell population and a nearly 100-fold increase in thymic cellularity to essentially normal levels. Together, these data strongly indicate that TCR beta chain-mediated developmental signals are transduced by CD3 components and provide potential insights into mechanisms by which TCR beta chain expression may effect this process.

Author-supplied keywords

  • Animals
  • Antibodies, Monoclonal
  • Antigens, CD3
  • Antigens, CD3: immunology
  • CD4-Positive T-Lymphocytes
  • CD4-Positive T-Lymphocytes: immunology
  • CD8-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes: immunology
  • DNA-Binding Proteins
  • Flow Cytometry
  • Mice
  • Mice, Mutant Strains
  • Proteins
  • Proteins: immunology
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, alpha-beta: immunology
  • Signal Transduction
  • Signal Transduction: immunology
  • Thymus Gland
  • Thymus Gland: cytology

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Authors

  • Y Shinkai

  • F W Alt

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