Identification of a novel subset of human circulating memory CD4+ T cells that produce both IL-17A and IL-4.

Abstract Background: IL-17A has been suggested to play a pathogenic role in bronchial asthma and other allergic disorders. Objective: Study of the relationship between human IL-17A–producing CD4 TH cells (TH17) and IL-4–producing CD4 TH (TH2) cells. Methods: T-cell clones generated from the CCR6CD161 fraction of human circulating CD4 T cells, which contains virtually all TH17 cells, as well as circulating CD4 T cells from both healthy subjects and patients with asthma, were assessed by flow cytometry for their cytokine production profile. Results: A small proportion of CCR6CD161CD4 T-cell clones showed the ability to produce both IL-17A and IL-4 (TH17/TH2). TH17/TH2 clones also produced IL-5, IL-8, IL-9, IL-13, IL-21, and IL-22 and displayed the ability to induce the in vitro secretion of IgE. A very few TH17/TH2 cells were found among circulating CD4 T cells from normal subjects, but their proportions were significantly increased in the circulation of patients with chronic asthma. TH17/TH2 cells could not be derived from naive umbilical cord blood CD4 T cells under any experimental condition. However, when circulating memory CCR6CD161CD4 T cells were cloned under appropriate polarizing conditions, TH17/TH2 clones originated in the presence of IL-4, suggesting that an IL-4–rich microenvironment may induce the shifting of memory TH17 cells into TH17/TH2 cells. Conclusion: Because of its peculiar functional properties and the increased numbers in the circulation of patients with bronchial asthma, this previously unknown population of TH17/TH2 cells may play some role in the pathogenesis of this disease. (J Allergy Clin Immunol 2010;125:222-230.) Questo articolo è stato selezionato dall'Editor della rivista per un'editoriale.