Interleukins 7 and 15 Maintain Human T Cell Proliferative Capacity through STAT5 Signaling

PLoS One. 2016 Nov 17;11(11):e0166280. doi: 10.1371/journal.pone.0166280. eCollection 2016.

Abstract

T lymphocytes require signals from self-peptides and cytokines, most notably interleukins 7 and 15 (IL-7, IL-15), for survival. While mouse T cells die rapidly if IL-7 or IL-15 is withdrawn, human T cells can survive prolonged withdrawal of IL-7 and IL-15. Here we show that IL-7 and IL-15 are required to maintain human T cell proliferative capacity through the STAT5 signaling pathway. T cells from humanized mice proliferate better if stimulated in the presence of human IL-7 or IL-15 or if T cells are exposed to human IL-7 or IL-15 in mice. Freshly isolated T cells from human peripheral blood lose proliferative capacity if cultured for 24 hours in the absence of IL-7 or IL-15. We further show that phosphorylation of STAT5 correlates with proliferation and inhibition of STAT5 reduces proliferation. These results reveal a novel role of IL-7 and IL-15 in maintaining human T cell function, provide an explanation for T cell dysfunction in humanized mice, and have significant implications for in vitro studies with human T cells.

MeSH terms

  • Animals
  • Cell Proliferation
  • Humans
  • Interleukin-15 / metabolism*
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • Interleukin-7 / metabolism*
  • Lymphocyte Activation
  • Lymphocyte Count
  • Mice
  • Phosphorylation
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction*
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / metabolism*
  • Up-Regulation

Substances

  • Interleukin-15
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-7
  • STAT5 Transcription Factor