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Rheumatology Advance Access originally published online on April 4, 2008
Rheumatology 2008 47(6):795-803; doi:10.1093/rheumatology/ken089
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© The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Increased IL-4+ CD8+ T cells in peripheral blood and autoreactive CD8+ T cell lines of patients with inflammatory arthritis

H. J. Baek1,2, L. Zhang2,3, L. B. Jarvis2 and J. S. H. Gaston2

1Department of Internal Medicine, Gachon University of Medicine and Science Gil Medical Center, 1198 Kuwol-dong, Namdong-gu, Incheon 405-760, South Korea, 2Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK and 3Department of Rheumatology and Immunology, Changzheng Hospital, Shanghai 200003, China.

Correspondence to: J. S. H. Gaston, Department of Medicine, Box 157, Level 5, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK. E-mail: jshg2{at}medschl.cam.ac.uk


  Abstract

Objective. To measure the frequencies of IL-4+ CD8+ T cells from patients with AS and RA, and to assess their clinical relevance and properties.

Methods. Peripheral blood (PB) and clinical data were obtained from 37 AS, 36 RA patients and 37 healthy controls. We also generated IL-4-producing CD8+ T cell lines and clones by co-culture with autologous dendritic cells. Using flow cytometry, we evaluated intracellular cytokine expression by T cells following stimulation with PMA and calcium ionophore. The phenotype and ability of the IL-4-producing CD8+ T cell clones to suppress IFN-{gamma} production were examined.

Results. The percentages of IL-4+ CD8+ T cells were higher in PB of patients with AS and RA than controls (medians 0.90 and 0.84% vs 0.30%). In RA, patients with active inflammation had an increased percentage of IL-4+ CD8+ T cells. Higher frequencies of IL-4+ CD8+ T cells were also found in CD8+ T cell lines established from patients with arthritis. Interestingly, most IL-4+ CD8+ T cells produced TNF-{alpha}. Cloning the CD8+ T cell lines yielded more IL-4-producing clones from AS (23%) and RA patients (14%) than from controls (7%). The ability to suppress IFN-{gamma} production was observed in 56% (AS) and 85% (RA) of IL-4-producing clones. Suppressive IL-4+ CD8+ T cell clones from RA patients showed a similar regulatory phenotype to the clones previously isolated from AS patients.

Conclusions. Expansion of IL-4+ CD8+ T cells, which may include precursors of a regulatory CD8+ T cell subset, may represent a general response to chronic joint inflammation.

KEY WORDS: CD8+ T cell, Interleukin-4, Tumour necrosis factor-{alpha}, Regulatory, Inflammatory arthritis, Ankylosing spondylitis, Rheumatoid arthritis

Submitted 24 August 2007; revised version accepted 5 February 2008.
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