Open Access

ARTICLE

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

Ursula Azizi-Semrad^1,*, Dagmar Krenbek^2,*, Günther Hofbauer¹, Georgios Karanikas³, Eduardo Maldonado-Gonzalez¹, Peter Pietschmann¹, Martin Willheim^1,4

1 Department of Pathophysiology, Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Austria
2 Institute of Pathology and Bacteriology, SMZ Otto Wagner Spital, Vienna, Austria
3 Department of Nuclear Medicine, Medical University of Vienna, Austria
4 Department of Laboratory Medicine, Wilhelminenspital Vienna

* Corresponding Author: M. Willheim,

European Cytokine Network 2010, 21(2), 105-115. https://doi.org/10.1684/ecn.2010.0190

Accepted 05 February 2010;

Abstract

The number of functional subsets of CD4+ T lymphocytes distinguished by their cytokine produc-tion has been extended in the last decade. The in vitro generation of a T cell subset characterized by IL-6production has resurrected the question of cytokine co-expression patterns in T cells. In order to delineatethese cells as a specific functional subpopulation in vivo, we profiled the cytokine production pattern of humanperipheral blood CD4+ T lymphocytes across established subsets. We provide evidence for a new T cell subsetTh6, 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 selectedtranscription factors, were determined in CD4+ T lymphocytes. Co-expression of two of these signaturecytokines used for the definition of functional subsets, e.g. IL-4, IFN-γ, IL-17 and IL-6 were observed, butnearly excluded the production of a third (or fourth) signature cytokine. In this respect, Th1 (key cytokineIFN-γ), Th2 (IL-4), Th6 (IL-6) and Th17 (IL-17) subsets can be defined, along with overlaps of any two ofthem. In contrast, TNF-α and IL-2 are not signature cytokines, but their absence or expression in single cellsintroduces further divisions across established subsets. Our study supports the concept of a further functionalT cell Th6 subset, and contributes to the reference cytokine profiles of healthy individuals relevant to furtherstudies in a variety of disease states.

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