Quantitative T cell subsets profile in peripheral blood from patients with idiopathic inflammatory myopathies: tilting the balance towards proinflammatory and pro-apoptotic subsets

Clin Exp Immunol. 2015 Mar;179(3):520-8. doi: 10.1111/cei.12475.

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(+) ).

Keywords: CD28null cells; Tfh cells; Th17 cells; idiopathic inflammatory myopathies; regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • Apoptosis / immunology
  • Female
  • Forkhead Transcription Factors / metabolism
  • Homeostasis
  • Humans
  • Immunophenotyping
  • Inflammation / immunology*
  • Male
  • Middle Aged
  • Muscles / immunology*
  • Muscles / pathology
  • Myositis / immunology*
  • Receptors, CCR6 / metabolism
  • Receptors, CXCR3 / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Regulatory / immunology*
  • Th17 Cells / immunology*

Substances

  • Antigens, CD
  • CCR6 protein, human
  • CXCR3 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptors, CCR6
  • Receptors, CXCR3