Notch Activity Influences the Alphabeta Versus Gammadelta T Cell Lineage Decision

Cell. 1997 Mar 21;88(6):833-43. doi: 10.1016/s0092-8674(00)81929-7.

Abstract

The choice between the alphabeta or gammadelta T cell fates is influenced by the production of functional, in-frame rearrangements of the TCR genes, but the mechanism that controls the lineage choice is not known. Here, we show that T cells that are heterozygous for a mutation of the Notch1 gene are more likely to develop as gammadelta T cells than as alphabeta T cells, implying that reduced Notch activity favors the gammadelta T cell fate over the alphabeta T cell fate. A constitutively activated form of Notch produces a reciprocal phenotype and induces thymocytes that have functional gammadeltaTCR gene rearrangements to adopt the alphabeta T cell fate. Our data indicate that Notch acts together with the newly formed T cell antigen receptor to direct the alphabeta versus gammadelta T cell lineage decision.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / physiology
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / cytology*
  • CD8-Positive T-Lymphocytes / physiology
  • Cell Differentiation / physiology
  • Cell Lineage / physiology
  • Female
  • Flow Cytometry
  • Gene Dosage
  • Gene Rearrangement
  • Hematopoietic Stem Cells / immunology
  • Heterozygote
  • Male
  • Membrane Proteins / genetics*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Notch
  • Recombinant Fusion Proteins / immunology
  • Signal Transduction / immunology
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Transgenes / immunology

Substances

  • Membrane Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • Receptors, Notch
  • Recombinant Fusion Proteins