Severe combined immunodeficiency. A model disease for molecular immunology and therapy.
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.
Fischer
Alain
A
INSERM U429, Hôpital Necker-Enfants Malades, Paris, France. alain.fischer@nck.ap-hop-paris.fr
Le Deist
Françoise
F
Hacein-Bey-Abina
Salima
S
André-Schmutz
Isabelle
I
Basile
Geneviève de Saint
Gde S
de Villartay
Jean-Pierre
JP
Cavazzana-Calvo
Marina
M
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