Ikaros sets thresholds for T cell activation and regulates chromosome propagation

Immunity. 1999 Mar;10(3):333-43. doi: 10.1016/s1074-7613(00)80033-3.


T cell activation involves the sustained accumulation of T cell receptor (TCR) and IL-2 receptor (IL-2R) mediated signaling events that promote cell cycle entry and progression. The Ikaros family of nuclear factors regulate this process by providing thresholds overcome by receptor signaling. T cells with reduced levels of Ikaros activity require fewer TCR engagement events for activation, exhibit a greater proliferative response to IL-2, and are less sensitive to inhibitors of TCR and IL-2R signaling. Upon T cell activation, Ikaros proteins localize in a higher-order chromatin structure where they colocalize with components of the DNA replication machinery. Proliferating T cells with reduced Ikaros activity display chromosome abnormalities. We propose that participation of Ikaros in higher-order chromatin structures controls cell cycle transitions and restricts DNA replication.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle / immunology*
  • Cell Cycle Proteins / physiology
  • Cell Division / genetics
  • Cell Division / immunology
  • Cell Nucleus / metabolism
  • Chromosome Aberrations / immunology
  • Chromosomes / physiology*
  • DNA-Binding Proteins*
  • Ikaros Transcription Factor
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation* / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mutation / immunology
  • S Phase / genetics
  • S Phase / immunology
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Interleukin-2
  • Transcription Factors
  • Zfpn1a1 protein, mouse
  • Ikaros Transcription Factor