Regulation of alphabeta/gammadelta T cell lineage commitment and peripheral T cell responses by Notch/RBP-J signaling

Immunity. 2004 May;20(5):611-22. doi: 10.1016/s1074-7613(04)00109-8.


RBP-J is a key mediator of Notch signaling that regulates a large spectrum of cell fate determinations. To elucidate the functions of Notch signaling in T cell development, we inactivated RBP-J specifically at two stages of T cell development by crossing RBP-J floxed mice with lck-cre or CD4-cre transgenic mice. The loss of RBP-J at an earlier developmental stage resulted in enhanced generation and accelerated emigration of gammadelta T cells, whereas alphabeta T cell development was arrested at the double-negative 3 stage. The loss of RBP-J at a later stage did not affect the absolute number or the production rate of CD4 or CD8-positive mature T cells but enhanced Th1 cell response and reduced CD4(+) T cell proliferation. Our data demonstrated that Notch/RBP-J signaling regulates gammadelta T cell generation and migration, alphabeta T cell maturation, terminal differentiation of CD4(+) T cells into Th1/Th2 cells, and activation of T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cell Lineage / immunology*
  • Cell Movement / immunology
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / immunology*
  • Flow Cytometry
  • Immune System / growth & development
  • Immunoblotting
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Immunohistochemistry
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Transgenic
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / immunology*
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Notch
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology
  • Thymus Gland / metabolism


  • DNA-Binding Proteins
  • Immunoglobulin J Recombination Signal Sequence-Binding Protein
  • Membrane Proteins
  • Nuclear Proteins
  • Rbpj protein, mouse
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Notch