Differentiation and functional analysis of human TH17 cells

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-1 beta expression in primary bronchial epithelial cells. TGF-beta, IL-1 beta, 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. (J Allergy Clin Immunol 2009;123:588-95.)