Human tumor-infiltrating Th17 cells have the capacity to differentiate into IFN-γ+ and FOXP3+ T cells with potent suppressive function

Jian Ye, Xinming Su, Eddy C. Hsueh, Yanping Zhang, Joyce M. Koenig, Daniel F. Hoft, Guangyong Peng

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Accumulating evidence suggests that Th17 cells and Tregs may exhibit development plasticity and that CD4+ Tregs can differentiate into IL-17-producing T cells; however, whether Th17 cells can reciprocally convert into Tregs has not been described. In this study, we generated Th17 clones from tumor-infiltrating T lymphocytes (TILs). We showed that Th17 clones generated from TILs can differentiate into IFN-γ-producing and FOXP3+ cells after in vitro stimulation with OKT3 and allogeneic peripheral blood mononuclear cells. We further demonstrated that T-cell receptor (TCR) engagement was responsible for this conversion, and that this differentiation was due to the epigenetic modification and reprogramming of gene expression profiles, including lineage-specific transcriptional factor and cytokine genes. In addition to expressing IFN-γ and FOXP3, we showed that these differentiated Th17 clones mediated potent suppressive function after repetitive stimulation with OKT3, suggesting that these Th17 clones had differentiated into functional Tregs. We further demonstrated that the Th17-derived Tregs, unlike naturally occurring CD4+CD25+ Tregs, did not reconvert back into Th17 cells even under Th17-biasing cytokine conditions. These results provide the critical evidence that human tumor-infiltrating Th17 cells can differentiate into Tregs and indicate a substantial developmental plasticity of Th17 cells.

Original languageEnglish
Pages (from-to)936-951
Number of pages16
JournalEuropean Journal of Immunology
Volume41
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • IL-17
  • T-cell development
  • Th17
  • Treg

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