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Quantitative T cell subsets profile in peripheral blood from patients with idiopathic inflammatory myopathies: tilting the balance towards proinflammatory and pro-apoptotic subsets
Authors:M. J. Ashbrook  K. L. McDonough  J. J. Pituch  P. L. Christopherson  T. T. Cornell  D. T. Selewski  T. P. Shanley  N. B. Blatt
Affiliation:Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico
Abstract:The role of T cells in idiopathic inflammatory myopathies (IIM) is not yet clear. Some alterations in certain subsets have been reported in inflamed muscle cells. However, a broad quantitative assessment of peripheral T cell subsets has not been evaluated. The aim of this study was to address the quantitative profile of potential pathogenic T cell subsets, namely follicular helper T cells (Tfh), T helper type 17 (Th17), CD28null and regulatory T cells (Tregs) in peripheral blood from IIM patients. Thirty IIM patients and 30 age- and gender-matched healthy donors were included. Peripheral blood mononuclear cells were isolated. T cell subsets were evaluated by flow cytometry, as follows: Tfh (CD4+CXCR5+) and its subsets Tfh1 (CXCR3+CCR6), Tfh2 (CXCR3CCR6), Tfh17 (CXCR3CCR6+), Th17 (CD4+IL17A+), CD28null (CD4+CD28CD244+) and Tregs (CD4+CD25highforkhead box protein 3 (FoxP3+); CD8+CD25highFoxP3+). Percentage, absolute numbers and mean fluorescence intensity were analysed. We found increased numbers of total Tfh cells (28 ± 8·16 versus 6·64 ± 1·29, P = 0·031) in IIM patients when compared to healthy controls. Moreover, this increment was dependent upon Tfh2 and Tfh17 (Tfh2:9·49 ± 2·19 versus 1·66 ± 0·46, P = 0·005; Tfh17 9·48 ± 2·83 versus 1·18 ± 0·21, P = 0·014). Also, IIM patients showed higher numbers of Th17 cells (30·25 ± 6·49 versus 13·46 ± 2·95, P = 0·031) as well as decreased number of Tregs (5·98 ± 1·61 versus 30·82 ± 8·38, P = 0·009). We also found an expansion of CD28null cells (162·88 ± 32·29 versus 64 ± 17·35, P = 0·015). Our data suggest that IIM patients are characterized by an expansion of peripheral proinflammatory T cells, such as Tfh and Th17, as well as pro-apoptotic CD28 null cells and a deficiency of suppressor populations of Tregs (CD4+ and CD8+).
Keywords:CD28null cells   idiopathic inflammatory myopathies   regulatory T cells   Tfh cells   Th17 cells
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