IL-27 increases the proliferation and effector functions of human naïve CD8+ T lymphocytes and promotes their development into Tc1 cells

Eur J Immunol. 2011 Jan;41(1):47-59. doi: 10.1002/eji.201040804. Epub 2010 Dec 9.

Abstract

IL-27 has been shown to exhibit both pro- and anti-inflammatory properties; it favors mouse naïve CD4(+) T-cell differentiation into Th1 cells to the detriment of Th17 and Th2 skewing and regulates IL-10 and IL-17 production by human CD4(+) T cells. Moreover, IL-27 promotes proliferation and cytotoxic functions of mouse CD8(+) T lymphocytes, but no data are available on human CD8(+) T cells. We investigated the impact of IL-27 on human CD8(+) T cells. In contrast to mouse T cells, the IL-27 receptor (IL-27R), composed of T cell cytokine receptor (TCCR) and gp130, was detected on a greater percentage of human CD8(+) than CD4(+) T cells and these proportions increased upon polyclonal activation. IL-27 induced rapid STAT1 and STAT3 signaling, enhanced STAT1 protein levels, and induced SOCS1 and SOCS3 expression in a STAT1-dependent manner by human CD8(+) T cells. Addition of IL-27 to α-CD3-activated naïve CD8(+) T cells significantly increased T-box transcription factor expression levels, cell proliferation, and IFN-γ and granzyme B production leading to increased CD8(+) T-cell-mediated cytotoxicity. These results demonstrate that IL-27, a rapidly produced cytokine by activated APC, has a profound impact on human naïve CD8(+) T cells, driving them to become highly efficient Tc1 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / analysis
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • CD3 Complex / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Carrier Proteins / analysis
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • Cytokine Receptor gp130 / analysis
  • Cytokine Receptor gp130 / immunology
  • Cytokine Receptor gp130 / metabolism
  • Granzymes / analysis
  • Granzymes / immunology
  • Granzymes / metabolism
  • Humans
  • Interferon-gamma / analysis
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Lymphocyte Activation / immunology*
  • STAT1 Transcription Factor / analysis
  • STAT1 Transcription Factor / immunology
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / analysis
  • STAT3 Transcription Factor / immunology
  • STAT3 Transcription Factor / metabolism
  • STAT5 Transcription Factor / immunology
  • STAT5 Transcription Factor / metabolism
  • T-Box Domain Proteins / analysis
  • T-Box Domain Proteins / immunology
  • T-Box Domain Proteins / metabolism
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Th1 Cells / immunology
  • Th1 Cells / metabolism

Substances

  • Antigens, Neoplasm
  • CD3 Complex
  • Carrier Proteins
  • IL6ST protein, human
  • Interleukin-17
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • STAT5 Transcription Factor
  • T-Box Domain Proteins
  • UBXN11 protein, human
  • Cytokine Receptor gp130
  • Interferon-gamma
  • Granzymes