Relationship between impaired apoptosis of lymphocytes and distribution of dendritic cells in peripheral blood and synovial fluid of children with juvenile idiopathic arthritis.

INTRODUCTION: The pathogenesis of juvenile idiopathic arthritis (JIA) is not fully understood. Recently the present authors described disturbed apoptosis of JIA lymphocytes in both peripheral blood (PB) and synovial fluid (SF) as well as an abnormal distribution of blood dendritic cells (BDCs) between the PB and SF in this disease. Possible relationships between these events during the development of JIA process are assessed here. MATERIALS AND METHODS: Lymphocyte apoptosis and BDC counts were assessed in the PB and SF of untreated JIA children. Lymphocyte apoptosis was analyzed by the Annexin-V/propydium iodide assay. Total DC (TDC) number was based on the sum of three BDC subpopulations determined using a panel of monoclonal antibodies against BDC antigens (BDCA): myeloid type 1 (mDC1, BDCA-1(+)/HLA-DR(+)/CD19(-)), myeloid type 2 (mDC2, BDCA-3(+)/HLA-DR(+)/CD14(-)), and plasmacytoid (pDC, BDCA-2(+)/HLA-DR(+)/CD123(+)). Cells were enumerated by the flow cytometric "single-platform" method. The concentration of tumor necrosis factor (TNF)-alpha and the distribution of particular lymphocyte subtypes in both PB and SF were also investigated. RESULTS: There was significant positive correlation between apoptosis of PB lymphocytes and SF TDC count (p=0.002) as well as SF TNF-alpha concentration (p=0.007). SF TNF-alpha levels also correlated with SF TDC count (p=0.003). Moreover, JIA SF was distinctly enriched with CD4+ and CD8+ T lymphocytes and included CD4(+)/CD25(high) cells as well. There was significant positive correlation between the number of CD4(+)/CD25(high) cells and SF JIA BDC count (p=0.015). CONCLUSIONS: These data suggest a possible link between impaired apoptosis of PB/SF lymphocytes and increased recruitment of PB BDCs to SF and other elements of the immune system in JIA, including regulatory CD4+/CD25high cells.