title: Human immune disorder arising from mutation of the alpha chain of the interleukin-2 receptor.
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 interleukin-2 receptor alpha chain (CD25), a subunit of the tripartite high-affinity receptor for interleukin 2. This immunodeficiency is characterized by decreased numbers of peripheral T cells displaying abnormal proliferation but normal B cell development. 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. While displaying normal development of CD2, CD3, CD4, and CD8 expression, CD25-deficient cortical thymocytes do not express CD1, and furthermore they fail to normally down-regulate levels of the anti-apoptotic protein bcl-2.
authors.affiliation: Department of Pediatrics, University of Toronto, ON, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Sharfe
authors.forename: H K
authors.initials: HK
authors.lastname: Dadi
authors.forename: M
authors.initials: M
authors.lastname: Shahar
authors.forename: C M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D015375:Receptors, Interleukin-2