Defect of regulatory T cells in patients with Omenn syndrome

Barbara Cassani, Pietro Luigi Poliani, Daniele Moratto, Cristina Sobacchi, Veronica Marrella, Laura Imperatori, Donatella Vairo, Alessandro Plebani, Silvia Giliani, Paolo Vezzoni, Fabio Facchetti, Fulvio Porta, Luigi D. Notarangelo, Anna Villa, Raffaele Badolato

Research output: Contribution to journalArticlepeer-review


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+ CD25high peripheral blood T cells in 2 of these patients. Results: 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. 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.

Original languageEnglish
Pages (from-to)209-216
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Issue number1-3
Publication statusPublished - Jan 2010


  • anergy and tolerance
  • FOXP3
  • Immunodeficiency
  • Omenn syndrome
  • regulatory T cells
  • thymus and the development of T lymphocytes
  • V(D)J recombination

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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