Journal
ANNALS OF THE RHEUMATIC DISEASES
Volume 68, Issue 12, Pages 1908-1915Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/ard.2008.100768
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Funding
- Margareta af Ugglas, Alex
- Wallstrom
- Borje Dahlin
- Tore Nilsson
- Magn. Bergvall
- Nanna Svartz
- Ake Wiberg
- King Gustaf the V:s 80 year Foundation
- Swedish Association
- Swedish Medical Association
- Swedish Research Council
- EU [LSHB CT-006-018661, LSHB CT-006-018662]
- Leukemia Research Fund
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Objective: To analyse the distribution of FOXP3+CD25+CD4+ regulatory T cells (Treg) in peripheral blood, synovial fluid and tissue of patients with rheumatic disease during relapse and after local treatment. Methods: FOXP3 expression was assessed by flow cytometry, immunohistochemistry, immunofluorescence and real-time polymerase chain reaction (RT-PCR). The functional suppressive capacity of Treg was analysed after co-culture with effector CD4+CD25-T cells through assessment of proliferation and cytokine secretion. Results: It was shown that FOXP3 protein and mRNA expression in synovial fluid T cells was not confined solely to CD25(bright) T cells as seen in blood, but included CD25(intermediate) and even CD25(neg) T cells. Indeed, synovial fluid CD25(high) T cells showed similar suppressive capacity as CD25(bright) T cells, indicating the presence of functional Treg in T cells with lower intensity of CD25. In synovial tissue, FOXP3+ cells were present in low numbers within T-cell infiltrates and decreased further after intra-articular glucocorticosteroid administration, in parallel with the general reduction in inflammation. Conclusions: Identification of synovial fluid FOXP3+ Treg with varying intensities of CD25 opens up possibilities for thorough characterisation of this important T-cell subset in the inflammatory compartment. However, only scarce synovial membrane expression of FOXP3 was found even in the absence of overt inflammation, suggesting that the synovial membrane is a site that would benefit therapeutically from Treg expansion.
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