title: Quantitative T cell subsets profile in peripheral blood from patients with idiopathic inflammatory myopathies: tilting the balance towards proinflammatory and pro-apoptotic subsets.
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), CD28(null) 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 (CXCR3(-) CCR6(-) ), Tfh17 (CXCR3(-) CCR6(+) ), Th17 (CD4(+) IL17A(+) ), CD28(null) (CD4(+) CD28(-) CD244(+) ) and Tregs (CD4(+) CD25(high) forkhead box protein 3 (FoxP3(+) ); CD8(+) CD25(high) FoxP3(+) ). 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 CD28(null) 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(+) ).
authors.affiliation: Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición, Salvador Zubirán, Mexico City, Mexico.
authors.forename: F
authors.initials: F
authors.lastname: Espinosa-Ortega
authors.forename: D
authors.initials: D
authors.lastname: Gómez-Martin
authors.forename: K
authors.initials: K
authors.lastname: Santana-De Anda
authors.forename: J
authors.initials: J
authors.lastname: Romo-Tena
authors.forename: P
authors.initials: P
authors.lastname: Villaseñor-Ovies
authors.forename: J
authors.initials: J
authors.lastname: Alcocer-Varela
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000276:immunology* / Q000473:pathology; D009220:Myositis / Q000276:immunology*; D054399:Receptors, CCR6 / Q000378:metabolism; D054367:Receptors, CXCR3 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D015703:Antigens, CD; C106311:CCR6 protein, human; C515187:CXCR3 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D054399:Receptors, CCR6; D054367:Receptors, CXCR3
keywords: CD28null cells; Tfh cells; Th17 cells; idiopathic inflammatory myopathies; regulatory T cells