Human Th17 cells comprise heterogeneous subsets including IFN-gamma-producing cells with distinct properties from the Th1 lineage

J Immunol. 2010 Jul 1;185(1):679-87. doi: 10.4049/jimmunol.1000366. Epub 2010 May 28.

Abstract

Th17 cells have been named after their signature cytokine IL-17 and accumulating evidence indicates their involvement in the induction and progression of inflammatory diseases. In addition to IL-17 single-producing T cells, IL-17/IFN-gamma double-positive T cells are found in significantly elevated numbers in inflamed tissues or blood from patients with chronic inflammatory disorders. Because IFN-gamma is the classical Th1-associated cytokine, the origin and roles of these subsets remain elusive. In this paper, we show that not only IL-17(+)/IFN-gamma(+) but also IFN-gamma(+) (IL-17(-)) cells arise under Th17-inducing condition and have distinct properties from the Th1 lineage. In fact, these populations displayed characteristics reminiscent to IL-17 single-producing cells, including production of IL-22, CCL20, and induction of antimicrobial gene expression from epithelial cells. Live sorted IL-17(+) and Th17-IFN-gamma(+) cells retained expression of IL-17 or IFN-gamma after culture, respectively, whereas the IL-17(+)/IFN-gamma(+) population was less stable and could also become IL-17 or IFN-gamma single-producing cells. Interestingly, these Th17 subsets became "Th1-like" cells in the presence of IL-12. These results provide novel insights into the relationship and functionality of the Th17 and Th1 subsets and have direct implications for the analysis and relevance of IL-17 and/or IFN-gamma-producing T cells present in patients' peripheral blood and inflamed tissues.

Publication types

  • Comparative Study

MeSH terms

  • Cell Lineage / immunology*
  • Cell Separation
  • Cells, Cultured
  • Cytokines / biosynthesis
  • Cytokines / blood
  • Cytokines / metabolism
  • Gene Expression Profiling
  • Humans
  • Immunophenotyping
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Inflammation Mediators / physiology
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / blood
  • Interferon-gamma / physiology
  • Interleukin-12 / blood
  • Interleukin-12 / metabolism
  • Interleukin-12 / physiology
  • Interleukin-17 / biosynthesis*
  • Interleukin-17 / blood
  • Interleukin-17 / physiology
  • T-Lymphocyte Subsets / classification
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Th1 Cells / classification
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism

Substances

  • Cytokines
  • Inflammation Mediators
  • Interleukin-17
  • Interleukin-12
  • Interferon-gamma