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

• Published in: Journal of allergy and clinical immunology 2009-03, Vol.123 (3), p.588-595
• Main Authors: Burgler, Simone, Ouaked, Nadia, Bassin, Claudio, Basinski, Tomasz M, Mantel, Pierre-Yves, Siegmund, Kerstin, Meyer, Norbert, Akdis, Cezmi A, Schmidt-Weber, Carsten B
• Format: Article
• Language: English
• Subjects: CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Differentiation - immunology; Cell Differentiation - physiology; Coculture Techniques; Epithelial Cells - immunology; Epithelial Cells - metabolism; Gene Expression; Humans; Interleukin-17 - immunology; Interleukin-17 - metabolism; Interleukin-1beta - immunology; Interleukin-1beta - metabolism; Interleukin-23 - immunology; Interleukin-23 - metabolism; Interleukin-6 - immunology; Interleukin-6 - metabolism; Natural Killer T-Cells - immunology; Natural Killer T-Cells - metabolism; Nuclear Receptor Subfamily 1, Group F, Member 3; Receptors, Retinoic Acid - immunology; Receptors, Retinoic Acid - metabolism; Receptors, Thyroid Hormone - immunology; Receptors, Thyroid Hormone - metabolism; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Transforming Growth Factor beta - immunology; Transforming Growth Factor beta - metabolism
• ISSN: 1097-6825
• DOI: 10.1016/j.jaci.2008.12.017

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. 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. 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. 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. 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.