Objectives (1) To compare the absolute T-cell numbers in bone marrow (BM) isolated from patients with rheumatoid arthritis (RA) and osteoarthritis (OA); (2) to measure the levels of soluble interleukin 15 (IL-15) and IL-7; (3) to analyse the expression of activation markers on T cells; (4) to analyse influence of IL-15 stimulation on T-cell proliferation.
Methods BM samples were obtained from patients undergoing joint replacement surgery. Concentrations of IL-15 and IL-7 were measured using specific ELISAs. The absolute number of T lymphocytes, their activation status and proliferation were evaluated by flow cytometry.
Results BM from patients with RA contained double the number of CD3 T cells in comparison with OA (6.1 vs 2.7 × 106 cells/ml, p<0.008). Ratio CD3CD4:CD3CD8 was increased in RA BM, clearly indicating accumulation of CD3CD4 cells. T cells obtained from patients with RA expressed higher level of early activation markers than from OA. Elevated levels of IL-15 were found in BM plasma from patients with RA in comparison with patients with OA (1304.5±956.3 pg/ml and 760±238.7 pg/ml respectively, p<0.01). These data were confirmed by immunohistochemistry of RA BM from regions proximal and distal to the joint. Although both CD3CD4 and CD3CD8 cells proliferated after IL-15 stimulation in vitro, CD3CD4 cells from patients with RA proliferated more vigorously than those from patients with OA, reflecting the composition of T-cell subsets in BM.
Conclusion These results suggest that locally overproduced IL-15 may be responsible for the activation and proliferation of T cells in situ, reflected by significantly increased number of activated T cells in RA BM, possibly contributing to the pathogenesis of RA.
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Funding European Community FP6 Project LSHB-CT-018661 AutoCure; grant No 2P05A 176 29 from the Polish Ministry of Science.
Patient consent Obtained.
Ethics approval This study was conducted with the approval of the Institute of Rheumatology Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.