Interleukin-17 facilitates the immune suppressor capacity of high-grade glioma-derived CD4 (+) CD25 (+) Foxp3 (+) T cells via releasing transforming growth factor beta

Scand J Immunol. 2014 Aug;80(2):144-50. doi: 10.1111/sji.12185.

Abstract

High-grade glioma is a malignant tumour; the pathogenesis is to be further investigated. Interleukin (IL)-17 is an inflammatory cytokine. Chronic inflammation is a pathological feature of cancer. This study aimed to characterize the glioma-derived IL-17(+) regulatory T cells (Treg). In this study, single cells were isolated from surgically removed high-grade glioma tissue and examined by flow cytometry. The immune suppressor effect of IL-17(+) Tregs on CD8(+) T cells was assessed in vitro. The results showed that abundant IL-17(+) Tregs were found in high-grade glioma tissue. The immune suppressor molecule, transforming growth factor (TGF)-beta, was detected in the IL-17(+) Tregs. The proliferation of CD8(+) T cells was suppressed by culturing with the IL-17(+) Tregs, which was partially abrogated by neutralizing antibodies of either TGF-beta or IL-17 and completely abrogated by neutralizing antibodies against both TGF-beta and IL-17. In conclusion, IL-17(+) Tregs exist in the high-grade glioma tissue; this subset of T cells can suppress CD8(+) T cell activities via releasing TGF-beta and IL-17.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Neutralizing / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Child
  • Female
  • Forkhead Transcription Factors / biosynthesis
  • Glioblastoma / immunology*
  • Glioblastoma / surgery
  • Humans
  • Immunosuppressive Agents
  • Inflammation / immunology
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Receptors, Interleukin-17 / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / immunology*
  • Transforming Growth Factor beta / metabolism
  • Young Adult

Substances

  • Antibodies, Neutralizing
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL2RA protein, human
  • Immunosuppressive Agents
  • Interleukin-17
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Interleukin-17
  • Transforming Growth Factor beta