title: 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(+) T(H) cells (T(H)17) and IL-4-producing CD4(+) T(H) (T(H)2) cells.
  
  
  METHODS
  T-cell clones generated from the CCR6(+)CD161(+) fraction of human circulating CD4(+) T cells, which contains virtually all T(H)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 (T(H)17/T(H)2). T(H)17/T(H)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 T(H)17/T(H)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. T(H)17/T(H)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, T(H)17/T(H)2 clones originated in the presence of IL-4, suggesting that an IL-4-rich microenvironment may induce the shifting of memory T(H)17 cells into T(H)17/T(H)2 cells.
  
  
  CONCLUSIONS
  Because of its peculiar functional properties and the increased numbers in the circulation of patients with bronchial asthma, this previously unknown population of T(H)17/T(H)2 cells may play some role in the pathogenesis of this disease.
authors.affiliation: Centre of Excellence DENOthe, University of Florence, Florence, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cosmi
authors.forename: Laura
authors.initials: L
authors.lastname: Maggi
authors.forename: Veronica
authors.initials: V
authors.lastname: Santarlasci
authors.forename: Manuela
authors.initials: M
authors.lastname: Capone
authors.forename: Elisa
authors.initials: E
authors.lastname: Cardilicchia
authors.forename: Francesca
authors.initials: F
authors.lastname: Frosali
authors.forename: Valentina
authors.initials: V
authors.lastname: Querci
authors.forename: Roberta
authors.initials: R
authors.lastname: Angeli
authors.forename: Andrea
authors.initials: A
authors.lastname: Matucci
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fambrini
authors.forename: Francesco
authors.initials: F
authors.lastname: Liotta
authors.forename: Paola
authors.initials: P
authors.lastname: Parronchi
authors.forename: Enrico
authors.initials: E
authors.lastname: Maggi
authors.forename: Sergio
authors.initials: S
authors.lastname: Romagnani
authors.forename: Francesco
authors.initials: F
authors.lastname: Annunziato
mesh_terms: D001249:Asthma / Q000276:immunology / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002999:Clone Cells; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism; D054399:Receptors, CCR6 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism
chemical_list: C106311:CCR6 protein, human; D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17; C527203:KLRB1 protein, human; D055651:NK Cell Lectin-Like Receptor Subfamily B; D054399:Receptors, CCR6; D015847:Interleukin-4