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

摘要: Bone marrow transplantation in human X-linked severe combined immunodeficiency (XSCID) without pretransplant conditioning results engraftment of donor T cells and reconstitution T-cell function but few, if any, B poor humoral immune function. Since bone remains the most effective treatment XSCID patients, better strategies are necessary to achieve optimum long-term results. Canine XSCID, like is due mutations common gamma chain (gamma c) gene has clinical immunologic features identical those making it a true homolog disease. We have successfully performed three dogs conditioning, using untreated from mixed lymphocyte culture-nonreactive normal littermates. Unlike experience all engrafted both attained full Normal percentages mitogenic responses were by 3 months posttransplant. CD3+ after expressed CD45RA isoform indicating that recent thymic emigrants derived immature progenitors. Serum IgG levels within range 5 Immunization with T-dependent antigen, bacteriophage phiX174, demonstrated antibody titers, memory, class-switching. Polymerase reaction (PCR) analysis c locus showed 100% circulating 30% 50% donor-derived. None developed clinically evident graft-versus-host disease (GVHD). Thus, canine provides model determine optimal conditions for develop test somatic therapy.