Interleukin-7 is required for CD4(+) T cell activation and autoimmune neuroinflammation

Clin Immunol. 2015 Dec;161(2):260-9. doi: 10.1016/j.clim.2015.08.007. Epub 2015 Aug 25.

Abstract

IL-7 is known to be vital for T cell homeostasis but has previously been presumed to be dispensable for TCR-induced activation. Here, we show that IL-7 is critical for the initial activation of CD4(+) T cells in that it provides some of the necessary early signaling components, such as activated STAT5 and Akt. Accordingly, short-term in vivo IL-7Rα blockade inhibited the activation and expansion of autoantigen-specific CD4(+) T cells and, when used to treat experimental autoimmune encephalomyelitis (EAE), prevented and ameliorated disease. Our studies demonstrate that IL-7 signaling is a prerequisite for optimal CD4(+) T cell activation and that IL-7R antagonism may be effective in treating CD4(+) T cell-mediated neuroinflammation and other autoimmune inflammatory conditions.

Keywords: EAE; IL-7; Signaling pathways; T cells.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cytokines / immunology
  • Cytokines / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Flow Cytometry
  • Humans
  • Interleukin-7 / deficiency
  • Interleukin-7 / genetics
  • Interleukin-7 / immunology*
  • Lymphocyte Activation / immunology*
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Mice, Transgenic
  • Phosphorylation / immunology
  • Proto-Oncogene Proteins c-akt / immunology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Interleukin-7 / immunology
  • Receptors, Interleukin-7 / metabolism
  • STAT2 Transcription Factor / immunology
  • STAT2 Transcription Factor / metabolism
  • Signal Transduction / immunology

Substances

  • Cytokines
  • Interleukin-7
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-7
  • STAT2 Transcription Factor
  • interleukin-7 receptor, alpha chain
  • Proto-Oncogene Proteins c-akt