title: Predominance of activated, clonally expanded T helper type 17 cells within the CD4+ T cell population in psoriatic lesions.
abstract: Recent evidence points to the T helper type 17 (Th17) subset as key in the pathogenesis of psoriasis, but cells of this type in lesions remain to be fully characterized. Here we isolated, enumerated, functionally tested and clonotyped the CD4(+) Th cell population ex vivo from lesional biopsies and paired peripheral blood samples from psoriasis patients. Th17 cells were over-represented dramatically in lesions from all patients, representing 49-93% of CD4(+) Th cells compared with 3-18% in blood. Most lesional Th17 cells produced interleukin (IL)-17A ex vivo without further stimulation and expressed the CD45RO(+) phenotype characteristic of activated or memory cells. There was no increase in 'natural' [CD25(hi) forkhead box protein 3 (FoxP3(+))] regulatory T cells in lesions versus peripheral blood, but there was enrichment of 'induced' IL-10(+) regulatory T cell numbers in biopsies from some patients. The lesional Th17 cells exhibited a bias in T cell receptor Vβ chain usage, suggestive of specific expansion by antigen. The therapeutic challenge is to overcome the dominance of overwhelming numbers of such antigen-specific Th17 cells in psoriatic lesions.
authors.affiliation: Section of Immunology and Infection, Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, UK. b.j.lewis@abdn.ac.uk
authors.forename: B J
authors.initials: BJ
authors.lastname: Lewis
authors.forename: S
authors.initials: S
authors.lastname: Rajpara
authors.forename: A M
authors.initials: AM
authors.lastname: Haggart
authors.forename: H M
authors.initials: HM
authors.lastname: Wilson
authors.forename: R N
authors.initials: RN
authors.lastname: Barker
authors.forename: A D
authors.initials: AD
authors.lastname: Ormerod
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D001769:Blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D007156:Immunologic Memory; D020381:Interleukin-17 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009928:Organ Specificity; D011565:Psoriasis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D012867:Skin / Q000276:immunology / Q000473:pathology; D037182:T-Cell Antigen Receptor Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D020381:Interleukin-17; D017493:Leukocyte Common Antigens