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J Allergy Clin Immunol. 2009 Mar;123(3):588-95, 595.e1-7. doi: 10.1016/j.jaci.2008.12.017.

Differentiation and functional analysis of human T(H)17 cells.

Author information

1
Swiss Institute for Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.

Abstract

BACKGROUND:

T(H)17 cells are of pathologic relevance in autoimmune disorders and presumably also in allergy and asthma. Regulatory T (Treg) cells, in contrast, suppress inflammatory and allergen-driven responses. Despite these disparate functions, both T-cell subsets have been shown to be dependent on TGF-beta for their development.

OBJECTIVE:

The aim of the study was to analyze the differentiation and function of human T(H)17 cells in comparison with other T(H) cell subsets.

METHODS:

Naive human CD4(+) T cells were differentiated in vitro, and gene expression was analyzed by means of quantitative real-time PCR, ELISA, and immunofluorescence. The function of T(H) cell subsets was assessed by monitoring the response of primary bronchial epithelial cells in coculture experiments.

RESULTS:

In vitro differentiated T(H)17 cells differ from Treg and other T(H) cells in their potency to induce IL-6 and IL-1beta expression in primary bronchial epithelial cells. TGF-beta, IL-1beta, IL-6, and IL-23 are necessary during T(H)17 cell differentiation to acquire these functions, including IL-17 production. In contrast, TGF-beta alone is necessary and sufficient to induce the transcription factor RORC2. This transcription factor, previously thought to be specific for T(H)17 cells, is also expressed in Treg cells, CD25(+) cells, cytotoxic T cells, and natural killer T cells.

CONCLUSION:

This study demonstrates mechanisms of differentiation to human T(H)17 cells, a subset that effectively and uniquely modulates the function of primary bronchial epithelial cells.

PMID:
19178935
DOI:
10.1016/j.jaci.2008.12.017
[Indexed for MEDLINE]

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