Severe combined immunodeficiency. A model disease for molecular immunology and therapy

Abstract

Summary: 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.