Defect of regulatory T cells in patients with Omenn syndrome.

[omenn syndrome]

Omenn syndrome (OS ) is an autosomal-recessive disorder characterized by severe immunodeficiency and T -cell-mediated autoimmunity . The disease is caused by hypomorphic mutations in recombination-activating genes that hamper the process of Variable (V ) Diversity (D ) Joining (J ) recombination , leading to the generation of autoreactive T cells . We have previously shown that in OS the expression of autoimmune regulator , a key factor governing central tolerance , is markedly reduced .Here , we have addressed the role of peripheral tolerance in the disease pathogenesis .We have analyzed forkhead box protein P 3 (FOXP 3 ) 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 CD 4 (+) CD 2 5 (high ) peripheral blood T cells in 2 of these patients .We have observed that CD 4 (+)CD 2 5 (high )T cells isolated ex vivo from patients with OS failed to suppress proliferation of autologous or allogenic CD 4 (+) responder T cells . Moreover , despite individual variability in the fraction of circulating FOXP 3 (+) CD 4 cells in patients with OS , the immunohistochemical analysis of FOXP 3 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 .

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Diseases presenting "which may actively concur to the development of autoimmune manifestations in the disease" symptom

omenn syndrome

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