Research article

Resting CD4⁺ effector memory T cells are precursors of bystander-activated effectors: a surrogate model of rheumatoid arthritis synovial T-cell function

Fionula M Brennan¹ , Nicola MG Smith¹ , Sally Owen¹ , Ching Li¹ , Parisa Amjadi¹ , Patricia Green¹ , Anna Andersson¹ , Andrew C Palfreeman¹ , Philippa Hillyer¹ , Andrew Foey² , Jonathan T Beech¹ and Marc Feldmann¹

¹Kennedy Institute of Rheumatology Division, Imperial College Faculty of Medicine, Aspenlea Road, London, W6 8LH, UK

²School of Biological Sciences, University of Plymouth, Drake Circus, Plymouth, PL4 8AA, UK

author email corresponding author email

Arthritis Research & Therapy 2008, 10:R36doi:10.1186/ar2390

Published:	19 March 2008

Abstract

Background

Previously we described a system whereby human peripheral blood T cells stimulated for 8 days in a cytokine cocktail acquired effector function for contact-dependent induction of proinflammatory cytokines from monocytes. We termed these cells cytokine-activated (Tck) cells and found that the signalling pathways elicited in the responding monocytes were identical whether they were placed in contact with Tck cells or with T cells isolated from rheumatoid arthritis (RA) synovial tissue.

Methods

Here, using magnetic beads and fluorescence-activated cell sorting, we extensively phenotype the Tck effector cells and conclude that effector function resides within the CD4⁺CD45RO⁺, CCR7^-, CD49d^high population, and that these cells are derived from the effector memory CD4⁺ T cells in resting blood.

Results

After stimulation in culture, these cells produce a wide range of T-cell cytokines, undergo proliferation and differentiate to acquire an extensively activated phenotype resembling RA synovial T cells. Blocking antibodies against CD69, CD18, or CD49d resulted in a reduction of tumour necrosis factor-α production from monocytes stimulated with CD4⁺CD45RO⁺ Tck cells in the co-culture assay. Moreover, blockade of these ligands also resulted in inhibition of spontaneous tumour necrosis factor-α production in RA synovial mononuclear cell cultures.

Conclusion

Taken together, these data strengthen our understanding of T-cell effector function, highlight the multiple involvement of different cell surface ligands in cell-cell contact and, provide novel insights into the pathogenesis of inflammatory RA disease.