A novel, dual cytokine-secretion assay for the purification of human Th22 cells that do not co-produce IL-17A

Allergy. 2016 Jan;71(1):47-57. doi: 10.1111/all.12768. Epub 2015 Nov 4.

Abstract

Background: Interleukin-22 is produced by certain T helper cells subsets (Th17, Th22) and at lower levels by γ-δ T cells, NKT and innate lymphoid cells. Th22 cells are unique immune cells that regulate tissue responses by IL-22 production. The exact discrimination between Th17 cells that co-produce IL-22 and single IL-22-producing Th22 cells has not been possible until the present study. Isolation of pure Th22 cells without co-expression of cytokines of other T-cell subsets is essential to better understand their function in humans. The aim of this study is the isolation and characterization of viable, human IL-22-producing CD4+ T cells that do not produce IL-17A.

Methods: Isolation of viable Th22 cells was performed with the combination of two cytokine secretion assays detecting IL-17A- and IL-22-producing cells in a single purification step.

Results: The newly developed cytokine secretion assay consists of anti-IL-22 and anti-IL-17A catch antibodies, which via biotin-streptavidin interaction are bound to the biotinylated surface of the target cell, and anti-IL-22 and IL-17A detection antibody labelled with a fluorescent dye, which detects cytokines bound to these catch antibodies. A unique population of human Th22 cells, which do not produce IL-17A, was sorted, and cytokine expression pattern was confirmed by quantitative PCR analysis and ELISA. The presented technique allows the detection and isolation of pure human Th22 cells.

Conclusions: This technique may allow the purification of any single cytokine-producing cell subset, and the combination of several different cytokine secretion assays can be used to purify and characterize novel and unique cell subsets.

Keywords: Interleukin-17A; Interleukin-22; cytokine-secretion assay; human Th17 cells; human Th22 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Surface / metabolism
  • Cell Separation* / methods
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Gene Expression
  • Humans
  • Interleukin-17 / biosynthesis
  • Interleukin-22
  • Interleukins / biosynthesis
  • Interleukins / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • T-Lymphocyte Subsets / metabolism*

Substances

  • Antigens, Surface
  • Cytokines
  • Interleukin-17
  • Interleukins
  • RNA, Messenger