Pre-T cell receptor (TCR) and TCR-controlled checkpoints in T cell differentiation are set by Ikaros

J Exp Med. 1999 Oct 18;190(8):1039-48. doi: 10.1084/jem.190.8.1039.

Abstract

T cell differentiation relies on pre-T cell receptor (TCR) and TCR signaling events that take place at successive steps of the pathway. Here, we show that two of these T cell differentiation checkpoints are regulated by Ikaros. In the absence of Ikaros, double negative thymocytes can differentiate to the double positive stage without expression of a pre-TCR complex. Subsequent events in T cell development mediated by TCR involving transition from the double positive to the single positive stage are also regulated by Ikaros. Nonetheless, in Ikaros-deficient thymocytes, the requirement of pre-TCR expression for expansion of immature thymocytes as they progress to the double positive stage is still maintained, and the T cell malignancies that invariably arise in the thymus of Ikaros-deficient mice are dependent on either pre-TCR or TCR signaling. We conclude that Ikaros regulates T cell differentiation, selection, and homeostasis by providing signaling thresholds for pre-TCR and TCR.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / immunology
  • Cell Lineage / immunology
  • DNA-Binding Proteins*
  • Flow Cytometry
  • Ikaros Transcription Factor
  • Mice
  • Mice, Inbred Strains
  • Receptors, Antigen, T-Cell / immunology*
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology*
  • Transcription Factors / genetics
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • Receptors, Antigen, T-Cell
  • Transcription Factors
  • Zfpn1a1 protein, mouse
  • Ikaros Transcription Factor