IL-7 downregulates IL-7Rα expression in human CD8 T cells by two independent mechanisms

Immunol Cell Biol. 2013 Feb;91(2):149-58. doi: 10.1038/icb.2012.69. Epub 2012 Dec 4.

Abstract

Interleukin (IL)-7 is an essential nonredundant cytokine, and throughout the lifespan of a T-cell signaling via the IL-7 receptor influences cell survival, proliferation and differentiation. It is therefore no surprise that expression of the IL-7 receptor alpha-chain (CD127) is tightly regulated. We have previously shown that IL-7 downregulates expression of CD127 at the cell surface and now elucidate the kinetics of that suppression and demonstrate that IL-7 downregulates CD127 transcripts and surface protein in primary human CD8 T cells by two separate pathways. We show that IL-7 induces the initial reduction in cell-surface CD127 protein independent of transcriptional suppression, which is delayed by 40-60 min. Although IL-7-mediated downregulation of CD127 transcripts is dependent on Janus kinase (JAK)/STAT5, the early downregulation of surface CD127 protein is independent of JAK activity. The data further illustrate that low levels of IL-7 induce smaller and transient decreases in CD127 transcripts and surface protein, whereas higher concentrations induce more profound and sustained suppression. Such flexibility in receptor expression likely allows for fine-tuned immune responses in human CD8 T cells in different microenvironments and in response to different immunological challenges.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / enzymology
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Dose-Response Relationship, Immunologic
  • Down-Regulation / drug effects*
  • Humans
  • Interleukin-7 / pharmacology*
  • Janus Kinases / metabolism
  • Jurkat Cells
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin-7 / genetics*
  • Receptors, Interleukin-7 / metabolism
  • STAT3 Transcription Factor / metabolism
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Time Factors
  • Transcription, Genetic / drug effects

Substances

  • Interleukin-7
  • RNA, Messenger
  • Receptors, Interleukin-7
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • interleukin-7 receptor, alpha chain
  • Phosphatidylinositol 3-Kinases
  • Janus Kinases