Abstract: 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-gamma 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(beta) 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.

Evidence of the transient nature of the Th17 phenotype of CD4+CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis / L.Cosmi; R.Cimaz; L.Maggi; V.Santarlasci; M.Capone; F.Borriello; F.Frosali; V.Querci; G.Simonini; G.Barra; MP.Piccinni; F.Liotta; R.De Palma; E.Maggi; S.Romagnani; F.Annunziato.. - In: ARTHRITIS AND RHEUMATISM. - ISSN 0004-3591. - STAMPA. - 63:(2011), pp. 2504-2515. [10.1002/art.30332]

Evidence of the transient nature of the Th17 phenotype of CD4+CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis.

COSMI, LORENZO;CIMAZ, ROLANDO;MAGGI, LAURA;SANTARLASCI, VERONICA;CAPONE, MANUELA;FROSALI, FRANCESCA;QUERCI, VALENTINA;SIMONINI, GABRIELE;PICCINNI, MARIE-PIERRE;LIOTTA, FRANCESCO;MAGGI, ENRICO;ROMAGNANI, SERGIO;ANNUNZIATO, FRANCESCO
2011

Abstract

Abstract: 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-gamma 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(beta) 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.
2011
63
2504
2515
L.Cosmi; R.Cimaz; L.Maggi; V.Santarlasci; M.Capone; F.Borriello; F.Frosali; V.Querci; G.Simonini; G.Barra; MP.Piccinni; F.Liotta; R.De Palma; E.Maggi; S.Romagnani; F.Annunziato.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/495684
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