Here, we have addressed the role of peripheral tolerance in the disease pathogenesis.
We have analyzed forkhead box protein P3 (FOXP3) expression in peripheral blood T cells of 4 patients with OS and in lymphoid organs of 8 patients with OS and have tested the suppressive activity of sorted CD4+ CD25high peripheral blood T cells in 2 of these patients.
We have observed that CD4+CD25highT cells isolated ex vivo from patients with OS failed to suppress proliferation of autologous or allogenic CD4+ responder T cells. Moreover, despite individual variability in the fraction of circulating FOXP3+ CD4 cells in patients with OS, the immunohistochemical analysis of FOXP3 expression in lymph nodes and thymus of patients with OS demonstrated a severe reduction of this cell subset compared with control tissues.
Overall, these results suggest a defect of regulatory T cells in OS leading to a breakdown of peripheral tolerance, which may actively concur to the development of autoimmune manifestations in the disease.