Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- mice

Cell. 1997 Jun 27;89(7):1011-9. doi: 10.1016/s0092-8674(00)80289-5.

Abstract

Signals from cytokine and antigen receptors play crucial roles during lymphocyte development. Mice lacking interleukin-7 receptor are lymphopenic, due to a defect in cell expansion at an early stage of differentiation, and the few mature T cells that develop in IL-7R-/- animals are functionally impaired. Both defects were rescued completely by overexpression of the anti-apoptosis protein Bcl-2. T cell progenitors lacking antigen receptor molecules are also blocked in differentiation and die, presumably because they fail to receive a positive signal via their pre-T cell receptor. Surprisingly, Bcl-2 did not promote survival or differentiation of T cells in rag-1-/- mice. These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / pharmacology
  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Apoptosis / immunology
  • CD4-Positive T-Lymphocytes / chemistry*
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / chemistry*
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • DNA-Binding Proteins / genetics*
  • Gene Expression / immunology
  • Genes, RAG-1 / genetics
  • Homeodomain Proteins*
  • Humans
  • Interleukin-7 / deficiency
  • Interleukin-7 / genetics
  • Lymph Nodes / cytology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitogens / pharmacology
  • Mutagenesis / immunology
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Receptors, Interleukin / genetics*
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-7
  • Signal Transduction / immunology
  • Spleen / cytology
  • Stem Cells / chemistry
  • Stem Cells / immunology
  • Thymus Gland / cytology
  • Transgenes / immunology

Substances

  • Antigens
  • Antigens, CD
  • DNA-Binding Proteins
  • Homeodomain Proteins
  • Interleukin-7
  • Mitogens
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Interleukin
  • Receptors, Interleukin-7
  • RAG-1 protein