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Human IL2RA null mutation mediates immunodeficiency with lymphoproliferation and autoimmunity
- Source :
- Clinical Immunology (Orlando, Fla.)
- Publication Year :
- 2013
- Publisher :
- Elsevier BV, 2013.
-
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.<br />Highlights ► CD25 deficiency leads to profound immune dysregulation. ► Preferential CD8+ T cell expansion and high cytokine serum levels were present. ► Proliferating CD8+ T cells infiltrated the skin but failed to respond to pathogens. ► CD4+FOXP3+CD127lowCD25null Tregs could be detected. ► Altered IL2 signaling events and failure of IL2 consumption contribute to autoimmunity.
- Subjects :
- T-Lymphocytes
T cell
Immunology
IPEX-like
Tregs
Autoimmunity
chemical and pharmacologic phenomena
Biology
medicine.disease_cause
CD25 deficiency
Article
Cell Line
CD25
Immunodeficiency
IL-2
Immune system
T-Lymphocyte Subsets
medicine
Humans
Immunology and Allergy
IL-2 receptor
Child
Cell Proliferation
Skin
Immunologic Deficiency Syndromes
Interleukin-2 Receptor alpha Subunit
FOXP3
hemic and immune systems
medicine.disease
medicine.anatomical_structure
Mutation
Leukocytes, Mononuclear
Cytokines
Female
CD8
Subjects
Details
- ISSN :
- 15216616
- Volume :
- 146
- Database :
- OpenAIRE
- Journal :
- Clinical Immunology
- Accession number :
- edsair.doi.dedup.....12bfa6b37d1354f528f8fe19f26ffe36