Antibody-facilitated chimeras. Stem cell allotransplantation using antihost major histocompatibility complex monoclonal antibodies instead of lethal irradiation for host conditioning.
Complete hemopoietic takeover between semiallogeneic adults can be accomplished by the administration of antihost major histocompatibility complex (MHC) monoclonal antibody (mAb) and donor stem cells. The recipients of such treatment are termed antibody-facilitated chimeras, and they have been produced in (BALB/cCr----(BALB/cCr X C3H/HeJ)F1 and DBA/2J----(DBA/2J X C3H/HeJ)F1 strain combinations. Donor stem cells can be derived from spleen, bone marrow, or T-cell-depleted bone marrow. Engraftment by donor hemopoietic cells can be facilitated by mAbs directed toward class I (anti-H-2Kk) or class II (anti-H-2I-Ak) MHC antigens of the host. By monitoring isozymes of glucose phosphate isomerase, it can be shown that the establishment of donor hemopoiesis is stable, persisting for more than a year without graft-versus-host disease. The effect of anti-MHC mAb on pluripotential stem cells was evaluated by the (colony-forming units-spleen) (CFU-S) assay. The number of CFU-S in target (H-2k) bone marrow was reduced by in vitro pretreatment with anti-H-2Kk mAb, but not with anti-H-2I-Ak mAb. In contrast, in vivo administration of either anti-H-2Kk or anti-H-2I-Ak mAb resulted in a marked decrease in the CFU-S capacity of relevant strain mice. These observations suggest that the target of the in vivo mAb treatment may be pluripotential stem cells--or perhaps the hemopoietic microenvironment.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002678:Chimera; D003114:Colony-Forming Units Assay; D006183:H-2 Antigens / Q000276:immunology; D008285:Major Histocompatibility Complex; D051379:Mice; D008815:Mice, Inbred Strains; D033581:Stem Cell Transplantation; D013997:Time Factors
D000911:Antibodies, Monoclonal; D006183:H-2 Antigens