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

Abstract

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)-α 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-α concentration (p=0.007). SF TNF-α 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 + /CD25 high cells.

Mesenchymal stromal cells for treatment of arthritis

“…In their synovial fluid we find around 5-10 Â 10 6 cells per ml with 1.2e2.4 Â 10 6 CD4þ cells per milliliter and 1.6-3.2 Â 10 6 CD8þ cells per milliliter. This is a little bit lower for CD4þ T-cells but the same for CD8þ cells as has been published before by others who calculated that synovial fluid of their JIA patients contains a median of 8.5 Â 10 6 CD4þ T-cells and 2.4 Â 10 6 CD8þ cells per millilitre [45]. In the synovial fluid (SF) of arthritic knees from 14 JIA patients we found mesenchymal stromal cells at a low rate: a median of 4 CFU-F per million SF cells with a maximum of 81 CFU-F. On the contrary normal (healthy) SF was reported to have 250 CFU-F per 1 million SF cells [7].…”

Th17 Transcription Factor RORC2 Is Inversely Correlated with FOXP3 Expression in the Joints of Children with Juvenile Idiopathic Arthritis

“…This is of interest, given the different patterns of expression of the 2 isoforms, as initially demonstrated in mice by He, et al 32 . The finding of increased RORC2 expression in SF might partly explain the impaired resistance to apoptosis seen in SF lymphocytes of JIA patients 43,44 since RORγt, the equivalent of RORC2 in mice, was shown to protect T cells from activation-induced cell death 32 . An antagonistic immune response between Treg and Th17 in situ in the joints of patients with JIA is in line with recent findings showing that Treg and Th17 cells are reciprocally regulated during differentiation 34 .…”

Identification of dendritic cells in the blood and synovial fluid of children with Juvenile Idiopathic Arthritis

“…Previous research has confirmed the presence of cells expressing CD1a or CD83 in the synovial tissue of patients with arthritis [9,10,29,30]. Smolewska et al confirmed expression of C83 on CD1c positive dendritic cells in the synovial fluid of JIA patients [17]. The CD83 molecule could be important not only when expressed on the cell surface, but also in soluble form.…”