title: Human IL-2 receptor alpha chain deficiency.
abstract: Profound cellular immunodeficiency occurs as the result of mutations in proteins involved in both the differentiation and function of mature lymphoid cells. We describe here a novel human immune aberration arising from a truncation mutation of the IL-2 receptor alpha chain (CD25), a subunit of the tripartite high-affinity receptor for IL-2. Decreased numbers of peripheral T cells displaying abnormal proliferation but normal B-cell development characterize this immunodeficiency. Extensive lymphocytic infiltration of tissues, including lung, liver, gut, and bone, is observed, accompanied by tissue atrophy and inflammation. Although mature T cells are present, the absence of CD25 does affect the differentiation of thymocytes. Although displaying normal development of CD2, CD3, CD4, and CD8 expression, CD25-deficient cortical thymocytes do not express CD1. Furthermore, they fail to down-regulate levels of bcl-2 and, subsequently, apoptosis in the thymus is markedly reduced, resulting in expansion of autoreactive clones in multiple tissues.
authors.affiliation: Department of Pediatrics, The Hospital for Sick Children and The University of Toronto, ON, Canada.
authors.forename: C M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000235:genetics; D017209:Apoptosis / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002675:Child, Preschool; D003241:Consanguinity; D017353:Gene Deletion; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D021122:Protein Subunits; D015375:Receptors, Interleukin-2 / Q000172:deficiency* / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000473:pathology
chemical_list: D015703:Antigens, CD; D021122:Protein Subunits; D015375:Receptors, Interleukin-2