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J Allergy Clin Immunol. 2010 Jan;125(1):209-16. doi: 10.1016/j.jaci.2009.10.023.

Defect of regulatory T cells in patients with Omenn syndrome.

Author information

1
Fondazione Humanitas per la Ricerca, Rozzano (MI), Italy.

Abstract

BACKGROUND:

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.

OBJECTIVE:

Here, we have addressed the role of peripheral tolerance in the disease pathogenesis.

METHODS:

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(+) CD25(high) peripheral blood T cells in 2 of these patients.

RESULTS:

We have observed that CD4(+)CD25(high)T 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.

CONCLUSION:

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.

PMID:
20109747
DOI:
10.1016/j.jaci.2009.10.023
[Indexed for MEDLINE]

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