IL-7 signaling must be intermittent, not continuous, during CD8⁺ T cell homeostasis to promote cell survival instead of cell death

Nat Immunol. 2013 Feb;14(2):143-51. doi: 10.1038/ni.2494. Epub 2012 Dec 16.


The maintenance of naive CD8(+) T cells is necessary for lifelong immunocompetence but for unknown reasons requires signaling via both interleukin 7 (IL-7) and the T cell antigen receptor (TCR). We now report that naive CD8(+) T cells required IL-7 signaling to be intermittent, not continuous, because prolonged IL-7 signaling induced naive CD8(+) T cells to proliferate, produce interferon-γ (IFN-γ) and undergo IFN-γ-triggered cell death. Homeostatic engagement of the TCR interrupted IL-7 signaling and thereby supported the survival and quiescence of CD8(+) T cells. However, CD8(+) T cells with insufficient TCR affinity for self ligands received prolonged IL-7 signaling and died during homeostasis. In this study we identified regulation of the duration of IL-7 signaling by homeostatic engagement of the TCR as the basis for in vivo CD8(+) T cell homeostasis.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Death / immunology
  • Cell Proliferation
  • Cell Survival / immunology
  • Gene Expression Regulation
  • Homeostasis / immunology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-7 / genetics*
  • Interleukin-7 / immunology
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics*
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction / immunology*
  • Time Factors


  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • interleukin-7, mouse
  • Interferon-gamma