title: Severe combined immunodeficiency. A model disease for molecular immunology and therapy.
abstract: Severe combined immunodeficiencies (SCIDs) consist of genetically determined arrest of T-cell differentiation. Ten different molecular defects have now been identified, which all lead to early death in the absence of therapy. Transplantation of allogeneic hematopoietic stem cells (HSCT) can restore T-cell development, thus saving the lives of SCID patients. In this review, the different characteristics of HSCT are discussed along with the available data regarding the long-term outcome. Transient thymopoiesis caused by an exhaustion of donor progenitor cells and possibly a progressive loss of thymus function can lead to a progressive decline in T-cell functions. The preliminary results of gene therapy show the correction of two SCID conditions. Based on the assumption that long-lasting pluripotent progenitor cells are transduced, these data suggest that gene therapy could overcome the long-term recurrence of the T-cell immunodeficiency. SCID is thus a disease model for experimental therapy in the hematopoietic system.
authors.affiliation: INSERM U429, Hôpital Necker-Enfants Malades, Paris, France. alain.fischer@nck.ap-hop-paris.fr
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Salima
authors.initials: S
authors.lastname: Hacein-Bey-Abina
authors.forename: Isabelle
authors.initials: I
authors.lastname: André-Schmutz
authors.forename: Geneviève de Saint
authors.initials: Gde S
authors.lastname: Basile
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: de Villartay
authors.forename: Marina
authors.initials: M
authors.lastname: Cavazzana-Calvo
mesh_terms: D015316:Genetic Therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007108:Immune Tolerance; D018448:Models, Immunological; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology* / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology