Details

Autor(en) / Beteiligte

• Cosmi, Lorenzo, MD
• Maggi, Laura, PhD
• Santarlasci, Veronica, PhD
• Capone, Manuela, BSc
• Cardilicchia, Elisa, BSc
• Frosali, Francesca, BSc
• Querci, Valentina, BSc
• Angeli, Roberta, PhD
• Matucci, Andrea, MD
• Fambrini, Massimiliano, MD
• Liotta, Francesco, MD
• Parronchi, Paola, MD
• Maggi, Enrico, MD
• Romagnani, Sergio, MD
• Annunziato, Francesco, PhD

Titel

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

Ist Teil von

• Journal of allergy and clinical immunology, 2010, Vol.125 (1), p.222-230.e4

Ort / Verlag

New York, NY: Elsevier Inc

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 (TH 17) and IL-4–producing CD4+ TH (TH 2) cells. Methods T-cell clones generated from the CCR6+ CD161+ fraction of human circulating CD4+ T cells, which contains virtually all TH 17 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 CCR6+ CD161+ CD4+ T-cell clones showed the ability to produce both IL-17A and IL-4 (TH 17/TH 2). TH 17/TH 2 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 TH 17/TH 2 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. TH 17/TH 2 cells could not be derived from naive umbilical cord blood CD4+ T cells under any experimental condition. However, when circulating memory CCR6+ CD161+ CD4+ T cells were cloned under appropriate polarizing conditions, TH 17/TH 2 clones originated in the presence of IL-4, suggesting that an IL-4–rich microenvironment may induce the shifting of memory TH 17 cells into TH 17/TH 2 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 TH 17/TH 2 cells may play some role in the pathogenesis of this disease.