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

• Published in: Arthritis research & therapy 2008-01, Vol.10 (2), p.R36-R36, Article R36
• Main Authors: Brennan, Fionula M, Smith, Nicola M G, Owen, Sally, Li, Ching, Amjadi, Parisa, Green, Patricia, Andersson, Anna, Palfreeman, Andrew C, Hillyer, Philippa, Foey, Andrew, Beech, Jonathan T, Feldmann, Marc
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; Arthritis, Rheumatoid - immunology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - immunology; Cell Lineage - immunology; Cells, Cultured; Cytokines - immunology; Cytokines - metabolism; Flow Cytometry; Humans; Immunologic Memory; Lymphocyte Activation - immunology; Monocytes - immunology; Monocytes - metabolism; Phenotype; Synovial Membrane - immunology; T-Lymphocyte Subsets - cytology; T-Lymphocyte Subsets - immunology
• ISSN: 1478-6354; 1478-6362; 1478-6354
• DOI: 10.1186/ar2390

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. 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. 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. 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.