ORCID
- Foey, Andrew: 0000-0003-0419-2268
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-, CD49dhigh 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-alpha 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-alpha 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.
DOI
10.1186/ar2390
Publication Date
2008-01-01
Publication Title
Arthritis Res Ther
Volume
10
Issue
2
Organisational Unit
School of Biomedical Sciences
Keywords
Antigens, CD, Arthritis, Rheumatoid, CD4-Positive T-Lymphocytes, Cell Lineage, Cells, Cultured, Cytokines, Flow Cytometry, Humans, Immunologic Memory, Lymphocyte Activation, Monocytes, Phenotype, Synovial Membrane, T-Lymphocyte Subsets
Recommended Citation
Brennan, F. M., Smith, N., Owen, S., Li, C., Amjadi, P., Green, P., Andersson, A., Palfreeman, A., Hillyer, P., Foey, A., Beech, J., & Feldmann, M. (2008) 'Resting CD4+ effector memory T cells are precursors of bystander-activated effectors: a surrogate model of rheumatoid arthritis synovial T-cell function.', Arthritis Res Ther, 10(2). Available at: https://doi.org/10.1186/ar2390
