title: Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity.
abstract: 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.
authors: San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Division of Regenerative Medicine, Stem Cells and Gene Therapy, San Raffaele Scientific Institute, Milan, Italy.
authors: Kevin
authors: K
authors: Goudy
authors: Didem
authors: D
authors: Aydin
authors: Federica
authors: F
authors: Barzaghi
authors: Eleonora
authors: E
authors: Gambineri
authors: Marina
authors: M
authors: Vignoli
authors: Sara
authors: S
authors: Ciullini Mannurita
authors: Claudio
authors: C
authors: Doglioni
authors: Maurilio
authors: M
authors: Ponzoni
authors: Maria Pia
authors: MP
authors: Cicalese
authors: Andrea
authors: A
authors: Assanelli
authors: Alberto
authors: A
authors: Tommasini
authors: Immacolata
authors: I
authors: Brigida
authors: Rosa Maria
authors: RM
authors: Dellepiane
authors: Silvana
authors: S
authors: Martino
authors: Sven
authors: S
authors: Olek
authors: Alessandro
authors: A
authors: Aiuti
authors: Fabio
authors: F
authors: Ciceri
authors: Maria Grazia
authors: MG
authors: Roncarolo
authors: Rosa
authors: R
authors: Bacchetta
mesh_terms: D015551:Autoimmunity / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D002648:Child; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology; D009154:Mutation; D012867:Skin / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D016207:Cytokines; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit