Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
CD4CD161 Cells with Th1 or Th17/Th1 Profile Accumulate in the Synovial Fluid of Patients with Juvenile Diopathic Arthritis and Correlate with Inflammation Parameters.
Cimaz1, Rolando, Cosmi2, L., Maggi2, L., Santarlasci2, V., Capone2, M., Borriello3, F., Frosali2, F.
A recently described subset of CD4+ T helper (Th) cells, named as type 17 Th (Th17) cells, has been suggested to be pathogenic in chronic inflammatory disorders, including rheumatoid arthritis and juvenile idiopathic arthritis. We wanted to investigate the phenotype and function of CD4+ T cells in synovial fluid (SF) of affected joints from children with juvenile idiopathic arthritis (JIA), and to establish a possible link with disease activity.
CD4+ T cells of peripheral blood (PB) and SF of 37 JIA patients, as well as of PB from 15 healthy children were analyzed for expression of CXCR3, CCR6, CD161 and production of IFNgand IL-17A. Intracellular cytokine production assays, cytokine secretion assays, and cell cultures were performed. CD161+IL-17+IFNg- and CD161+IL-246-IFNg+ cells derived from PB of one healthy donor and the SF of one JIA patient were also cloned. RORC expression was evaluated by real-time quantitative RT-PCR in FACS sorted populations. Spectratyping and clonotypic analyses on different T cell subsets were performed.
Numbers of CD4+CD161+, showing either the Th1 (IFNg-producing) or the Th17/Th1 (producing both IFN-g and IL-17A) phenotype, were higher in SF than in PB from JIA children. The few Th17 cells from SF of JIA spontaneously shifted in vitro to Th1 cells, whereas Th17 cells from PB of healthy children did it only in presence of SF, this effect being neutralized by blocking IL-12 activity. Spectratyping and clonotypic analyses showed a similar skewing of the TCR-BV repertoire in both SF-derived CD161+Th17 and CD161+Th1 cells from the same JIA patient. The frequencies of CD4+CD161+ cells, particularly of those showing the Th17/Th1 phenotype, in SF of JIA positively correlated with levels of erythrocyte sedimentation rate and C-reactive protein.
These findings suggest that a shifting of CD4+CD161+Th17 cells into Th17/Th1 or Th1 cells in the SF from affected joints of JIA can occur, and indicate that the accumulation of these latter correlates with parameters of inflammation, thus supporting the hypothesis that these cells play a role in disease activity.
To cite this abstract, please use the following information:
Cimaz, Rolando, Cosmi, L., Maggi, L., Santarlasci, V., Capone, M., Borriello, F., et al; CD4CD161 Cells with Th1 or Th17/Th1 Profile Accumulate in the Synovial Fluid of Patients with Juvenile Diopathic Arthritis and Correlate with Inflammation Parameters. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :246