Cutting edge: an alternative pathway of CD4+ T cell differentiation is induced following activation in the absence of gamma-chain-dependent cytokine signals

J Immunol. 2006 Feb 15;176(4):2059-63. doi: 10.4049/jimmunol.176.4.2059.


This report addresses the role of gamma-chain cytokine signals in regulating CD4(+) T cell differentiation following activation. Using murine CD4(+) T cells lacking the Jak3 tyrosine kinase, we show that activation of these cells in the absence of gamma-chain-dependent cytokine signals induces an alternative pathway of T cell differentiation. Specifically, activated Jak3(-/-) CD4(+) T cells produce IL-10, TGF-beta, and IFN-gamma, but not IL-2 or IL-4, and are unable to proliferate in vitro. In addition, Jak3(-/-) CD4(+) T cells express high levels of programmed death-1 and lymphocyte activation gene-3 and modestly suppress the proliferation of wild-type CD4(+) T cells in coculture assays. Together, these features demonstrate a striking similarity between Jak3(-/-) CD4(+) T cells and the regulatory T cells that have been shown to suppress immune responses in vitro and in vivo. We conclude that Jak3 is a critical component of signaling pathways that regulate T cell differentiation into effector vs regulatory lineages.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation*
  • Cell Proliferation
  • Cells, Cultured
  • Cytokines / chemistry*
  • Cytokines / immunology
  • Cytokines / physiology*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Homeostasis
  • Janus Kinase 3
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Protein-Tyrosine Kinases / deficiency
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism


  • Cytokines
  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • Protein-Tyrosine Kinases
  • Jak3 protein, mouse
  • Janus Kinase 3