title: Human T cell immunodeficiency: when signal transduction goes wrong.
abstract: Severe combined immunodeficiency (SCID) is a heterogeneous group of diseases that are invariably fatal in infancy unless treated by hematopoietic stem cell replacement. For many years we have worked to better manage patients affected by SCID through rapid and accurate diagnosis followed by treatment aimed at achieving long-lasting immune reconstitution. By extensive immunological, biochemical, and genetic studies of patient samples, and with the realization of differences between human and murine T cell development, we have successfully been able to identify some of the molecular defects causing SCID. Among these discoveries, we described the first mutated signal transduction protein in T cells (ZAP-70); the first genetic defect leading to SCID and autoimmune phenomena (IL2R alpha); and, recently, the critical importance of CD3delta in the development of T cells. Our efforts have significantly advanced the understanding of the role of some of the signal-transducing proteins in T cell maturation and function. This review summarizes several of these discoveries and some of their impact on our understanding of T cells development, function, and homeostasis in humans.
authors.affiliation: Division of Immunology/Allergy and the Infection, Immunity, Injury and Repair Program, The Research Institute and The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eyal
authors.initials: E
authors.lastname: Grunebaum
authors.forename: Nigel
authors.initials: N
authors.lastname: Sharfe
authors.forename: Chaim M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000502:physiology; D053616:Janus Kinase 3; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology; D016511:Severe Combined Immunodeficiency / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics*; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000502:physiology*
chemical_list: D007378:Interleukins; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; C507935:Jak3 protein, mouse; D053616:Janus Kinase 3; D051746:ZAP-70 Protein-Tyrosine Kinase