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Regulatory IL4+CD8+ T cells in patients with ankylosing spondylitis and healthy controls
  1. L Zhang1,2,
  2. L B Jarvis2,
  3. H-J Baek2,3,
  4. J S Hill Gaston2
  1. 1
    Department of Rheumatology and Immunology, Changzheng Hospital, Shanghai, China
  2. 2
    Department of Medicine, University of Cambridge Clinical School, Addenbrooke’s Hospital, Cambridge, UK
  3. 3
    Department of Internal Medicine, Gachon University of Medicine and Science, Gil Medical Center, Namdong-gu, Incheon, South Korea
  4. 4
    lbd20@medschl.cam.ac.uk
  1. Professor J S H Gaston, Department of Medicine, Box 157, Level 5, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 2QQ, UK; jshg2{at}medschl.cam.ac.uk

Abstract

Objectives: Interleukin (IL)4+CD8+ regulatory T cells (Treg) obtained from peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) by coculture with autologous dendritic cells (DC) have been previously described. In the present work, the proportions of IL4+CD8+ T cells in PB from patients with AS and controls are examined; in addition the conditions required for the generation of IL4+CD8+ Treg cells and their frequency in T cell lines from patients with AS and controls are investigated.

Methods: CD8+ T cells were either stimulated non-specifically ex vivo and intracellular cytokines examined, or cocultured with DC and other stimuli, for 2 weeks. The resulting lines were analysed for cytokine expression. Clones derived from these lines were tested for regulatory function.

Results: PBMCs from patients with AS and from human leukocyte antigen (HLA)-B27+ healthy controls contained a higher frequency of IL4+CD8+ T cells than those from HLA-B27− controls. Likewise, CD8+ T cell lines obtained by coculture with DC contained a higher ratio of IL4+ to interferon (IFN)γ+ cells when obtained from patients with AS or HLA-B27+ controls. T cell clones obtained from these lines showed regulatory activity. Outgrowth of IL4+ CD8+ T cells required contact with DC, but not maturation with lipopolysaccharide (LPS); allogeneic DC were also effective. Coculture with lymphoblastoid cells, or anti-CD3/CD28 microbeads, produced only expansion of IFNγ-producing CD8+ T cells.

Conclusions: The higher proportion of CD8+ cells which can produce IL4 in PB and in expanded CD8+ T cell lines suggests an altered pattern of CD8+ T cell differentiation in AS and in HLA-B27+ healthy individuals. This predisposition to generate IL4+CD8+ T cells may play a role in pathogenesis of spondyloarthritis.

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Footnotes

  • Competing interests: None.

  • Funding: This work was supported by the Henry Smith’s Charity and by funding provided to the NIHR Cambridge Biomedical Research Centre.

  • Ethics approval: Ethics approval was given by Addenbrooke’s Hospital Local Research Ethical Committee.

  • ▸ Additional data (Supplementary figs 1–3 and supplementary information) are published online only at http://ard.bmj.com/content/vol68/issue8

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