Resolution and relapse of osteopetrosis in mice transplanted with myeloid tissue of variable histocompatibility

Abstract

Osteopetrotic microphthalmic mice (mi/mi) were treated by injections of suspensions of myeloid tissue, newborns i.p., and weanlings i.v. Donated syngeneic material effected permanent cure of oteopetrosis provided that the dose was large enough (10(8) cells of bone marrow). H-2-compatible allogeneic bone marrow was initially as effective, but relapse ensued in immunocompetent mice. H-2-incompatible marrow was ineffecitve except in one set of newborn tolerant mice. Total body X-radiation in sublethal doses to recipients allowed permanent cure with H-2-compatible, and, in one circumstance, with H-2-incompatible marrow in smaller doses. The best results were obtained after lethal irradiation and the smaller dose of marrow. Results were checked by chromosome assay demonstrating that cure or relapse was correlated with permanent take or rejection, respectively, of a transplant in a recipient's bone marrow. Retention of donor lymphocytes alone was not associated with effective bony resorption; the candidate cell line for effectiveness remains the haematopoietic stem cell-monocyte-tissue phagocyte.