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): R36, 2008.
Article
in En
| MEDLINE
| ID: mdl-18353171
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arthritis, Rheumatoid
/
Synovial Membrane
/
CD4-Positive T-Lymphocytes
/
T-Lymphocyte Subsets
/
Cell Lineage
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Arthritis Res Ther
Journal subject:
REUMATOLOGIA
Year:
2008
Document type:
Article
Affiliation country:
United kingdom