Full Immunologic Reconstitution Following Nonconditioned Bone Marrow Transplantation for Canine X-Linked Severe Combined Immunodeficiency

Bone marrow transplantation in human X-linked severe Normal percentages of T cells and T-cell mitogenic recombined immunodeficiency (XSCID) without pretransplant sponses were attained by 3 months posttransplant. CD3 T conditioning results in engraftment of donor T cells and recells after transplantation expressed the CD45RA isoform constitution of T-cell function but engraftment of few, if any, indicating that the cells were recent thymic emigrants dedonor B cells and poor reconstitution of humoral immune rived from immature progenitors. Serum IgG levels were function. Since bone marrow transplantation remains the within normal range by 5 months posttransplant. Immunizamost effective treatment of XSCID patients, better strategies tion with the T-dependent antigen, bacteriophage fX174, are necessary to achieve optimum long-term results. Canine demonstrated normal antibody titers, immunologic memXSCID, like human XSCID, is due to mutations in the comory, and class-switching. Polymerase chain reaction (PCR) mon g chain (gc) gene and has clinical and immunologic analysis of the gc locus showed that 100% of circulating T features identical to those of human XSCID, making it a true cells and 30% to 50% of circulating B cells were donor-dehomolog of the human disease. We have successfully perrived. None of the dogs developed clinically evident graftformed bone marrow transplantation in three XSCID dogs versus-host disease (GVHD). Thus, canine XSCID provides a without pretransplant conditioning, using untreated bone model to determine the optimal conditions for bone marrow marrow cells from mixed lymphocyte culture–nonreactive transplantation in human patients, and to develop and test normal littermates. Unlike the experience in human XSCID strategies for somatic gene therapy. patients, all three dogs engrafted both donor B and T cells q 1997 by The American Society of Hematology. and attained full reconstitution of immunologic function.