Open AccessEvidence of the transient nature of the Th17 phenotype of CD4+CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis
Author(s) -
Cosmi Lorenzo,
Cimaz Rolando,
Maggi Laura,
Santarlasci Veronica,
Capone Manuela,
Borriello Francesco,
Frosali Francesca,
Querci Valentina,
Simonini Gabriele,
Barra Giusi,
Piccinni Marie Pierre,
Liotta Francesco,
De Palma Raffaele,
Maggi Enrico,
Romagnani Sergio,
Annunziato Francesco
Publication year - 2011
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.30332
Subject(s) - erythrocyte sedimentation rate , synovial fluid , arthritis , immunology , phenotype , immunophenotyping , medicine , cxcr3 , interleukin 17 , c c chemokine receptor type 6 , juvenile , inflammation , flow cytometry , biology , pathology , gene , biochemistry , alternative medicine , chemokine , chemokine receptor , osteoarthritis , genetics
Objective To investigate the phenotype and function of CD4+ T cells in synovial fluid (SF) from the affected joints of children with oligoarticular‐onset juvenile idiopathic arthritis (JIA), and to establish a possible link with disease activity. Methods CD4+ T cells were obtained from the peripheral blood (PB) and SF of 23 children with oligoarticular‐onset JIA, as well as from the PB of 15 healthy children. The cells were analyzed for the expression of CXCR3, CCR6, and CD161 and for the production of interferon‐γ and interleukin‐17A (IL‐17A). Spectratyping and clonotype analyses were performed to assess different T cell subsets. Results The numbers of CD4+CD161+ cells showing either the Th1 or the Th17/Th1 phenotype were higher in the SF than in the PB of children with JIA. The few Th17 cells from JIA SF underwent a spontaneous shift to the Th1 phenotype in vitro, whereas Th17 cells from the PB of healthy children shifted only in the presence of JIA SF; this effect was neutralized by antibody blockade of IL‐12 activity. Spectratyping and clonotype analyses showed a similar skewing of the T cell receptor V β repertoire in both CD161+ Th17 cells and CD161+ Th1 cells derived from the SF of the same JIA patient. The frequencies of CD4+CD161+ cells, particularly the Th17/Th1 cells, in the JIA SF positively correlated with the erythrocyte sedimentation rate and levels of C‐reactive protein. Conclusion These findings suggest that a shifting of CD4+CD161+ T cells from Th17 to the Th17/Th1 or Th1 phenotype can occur in the SF of children with oligoarticular‐onset JIA, and indicate that the accumulation of these cells is correlated with parameters of inflammation. Thus, the results support the hypothesis that these cells may play a role in JIA disease activity.