Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity

Kevin Goudy, Didem Aydin, Federica Barzaghi, Eleonora Gambineri, Marina Vignoli, Sara Ciullini Mannurita, Claudio Doglioni, Maurilio Ponzoni, Maria Pia Cicalese, Andrea Assanelli, Alberto Tommasini, Immacolata Brigida, Rosa Maria Dellepiane, Silvana Martino, Sven Olek, Alessandro Aiuti, Fabio Ciceri, Maria Grazia Roncarolo, Rosa Bacchetta

Research output: Contribution to journalArticlepeer-review


Cell-surface CD25 expression is critical for maintaining immune function and homeostasis. As in few reported cases, CD25 deficiency manifests with severe autoimmune enteritis and viral infections. To dissect the underlying immunological mechanisms driving these symptoms, we analyzed the regulatory and effector T cell functions in a CD25 deficient patient harboring a novel IL2RA mutation. Pronounced lymphoproliferation, mainly of the CD8+ T cells, was detected together with an increase in T cell activation markers and elevated serum cytokines. However, Ag-specific responses were impaired in vivo and in vitro. Activated CD8+STAT5+ T cells with lytic potential infiltrated the skin, even though FOXP3+ Tregs were present and maintained a higher capacity to respond to IL-2 compared to other T-cell subsets. Thus, the complex pathogenesis of CD25 deficiency provides invaluable insight into the role of IL2/IL-2RA-dependent regulation in autoimmunity and inflammatory diseases.

Original languageEnglish
Pages (from-to)248-261
Number of pages14
JournalClinical Immunology
Issue number3
Publication statusPublished - Mar 2013


  • Autoimmunity;
  • CD25;
  • IL-2
  • Immunodeficiency;
  • IPEX-like;
  • Tregs;

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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