Signaling by intrathymic cytokines, not T cell antigen receptors, specifies CD8 lineage choice and promotes the differentiation of cytotoxic-lineage T cells

Nat Immunol. 2010 Mar;11(3):257-64. doi: 10.1038/ni.1840. Epub 2010 Jan 31.


Immature CD4(+)CD8(+) (double-positive (DP)) thymocytes are signaled via T cell antigen receptors (TCRs) to undergo positive selection and become responsive to intrathymic cytokines such as interleukin 7 (IL-7). We report here that cytokine signaling is required for positively selected thymocytes to express the transcription factor Runx3, specify CD8 lineage choice and differentiate into cytotoxic-lineage T cells. In DP thymocytes genetically engineered to be cytokine responsive, IL-7 signaling induced TCR-unsignaled DP thymocytes to express Runx3 and to differentiate into mature CD8(+) T cells, completely circumventing positive selection. We conclude that TCR-mediated positive selection converts DP cells into cytokine-responsive thymocytes, but it is subsequent signaling by intrathymic cytokines that specifies CD8 lineage choice and promotes differentiation into cytotoxic-lineage T cells.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Cell Count
  • Cell Differentiation / immunology
  • Cell Lineage
  • Core Binding Factor Alpha 3 Subunit / immunology
  • Cytokines / immunology*
  • Flow Cytometry
  • Interleukin-7 / immunology
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • STAT5 Transcription Factor / immunology
  • Signal Transduction
  • T-Lymphocytes, Cytotoxic / immunology*


  • Core Binding Factor Alpha 3 Subunit
  • Cytokines
  • Interleukin-7
  • Runx3 protein, mouse
  • STAT5 Transcription Factor