ANTIBODY-FACILITATED CHIMERAS

Abstract

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; they have been produced in (BALB/cCr .fwdarw. BALB/cCR .times. C3H/HeJ)F1 and DBA/2J .fwdarw. (DBA/2J .times. C3H/HeJ)F1 [mouse] 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 mAb directed toward class I (anti-H-2Kk) or classII (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 > 1 yr without graft-vs.-host disease. The effect of anti-MHC mAb on pluripotential stem cells was evaluated by the (colony-forming units-spleen) (CFU-S [pluripotential stem cells]) 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 vivo administration of anti-H-2Kk or anti-H-2I-Ak mAb resulted in a marked decrease in the CFU-S capacity of relevant strain mice. The target of the in vivo mAb treatment may be pluripotential stem cells, or perhaps the hemopoietic microenvironment.