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Cytokine profiling of human peripheral blood CD4+ Tlymphocytes reveals a new Th-subpopulation (Th6) characterized by IL-6


European Cytokine Network. Volume 21, Number 2, 105-15, June 2010, research article

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Author(s) : Ursula Azizi-Semrad, Dagmar Krenbek, Günther Hofbauer, Georgios Karanikas, Eduardo Maldonado-Gonzalez, Peter Pietschmann, Martin Willheim

Summary : The number of functional subsets of CD4+ T lymphocytes distinguished by their cytokine production has been extended in the last decade. The in vitro generation of a T cell subset characterized by IL-6 production has resurrected the question of cytokine co-expression patterns in T cells. In order to delineate these cells as a specific functional subpopulation in vivo, we profiled the cytokine production pattern of human peripheral blood CD4+ T lymphocytes across established subsets. We provide evidence for a new T cell subset Th6, with an IL-6 signature. Freshly isolated PBMC were analyzed using intracellular cytokine detection (IDC). Cytokine co-expression patterns of up to three cytokines, as well as their correlation with selected transcription factors, were determined in CD4+ T lymphocytes. Co-expression of two of these signature cytokines used for the definition of functional subsets, e.g. IL-4, IFN-γ, IL-17 and IL-6 were observed, but nearly excluded the production of a third (or fourth) signature cytokine. In this respect, Th1 (key cytokine IFN-γ), Th2 (IL-4), Th6 (IL-6) and Th17 (IL-17) subsets can be defined, along with overlaps of any two of them. In contrast, TNF-α and IL-2 are not signature cytokines, but their absence or expression in single cells introduces further divisions across established subsets. Our study supports the concept of a further functional T cell Th6 subset, and contributes to the reference cytokine profiles of healthy individuals relevant to further studies in a variety of disease states.

Keywords : intracellular cytokine detection, flow cytometry, IL-2, IL-6, TNF-α, GATA-3

 

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