Studies on the use of nonhuman primates to determine the DR status of the human hematopoietic stem cell.
Monoclonal antibodies that recognize monomorphic determinants of human DR are potentially useful for the in vitro elimination of malignant cells from marrow for use in autologous transplantation. While DR is expressed on normal hematopoietic progenitor cells and the cells of the majority of the hematologic and lymphoid malignancies, there is the possibility that DR may not be expressed on the hematopoietic stem cells responsible for marrow regeneration after transplantation. To resolve the uncertainty regarding the DR status of the human stem cell, we determined whether antihuman DR monoclonal antibodies recognized analogous antigens on nonhuman primate hematopoietic progenitor cells to determine an appropriate animal transplant model. We used antihuman DR plus C'-mediated lysis of marrow progenitor cells as an indicator of whether the analogous nonhuman primate cells express similar antigens. Using two potent C'-fixing anti-DR monoclonal antibodies separately (5F3, AMG-12), human progenitor cells are reduced by 90%-100%. The range of progenitor cell depletion varied more widely with the nonhuman primates studied: 80%-99% with cells from the chimpanzee, 48%-100% with cells from the orangutan, and 62%-100% with cells from the rhesus monkey. Despite this, the majority of animals yielded results identical to that seen with human cells. We concluded that autologous transplantation with DR-depleted rhesus bone marrow into a lethally irradiated animal would be a practical and expeditious means to determine the DR status of the cell responsible for marrow regeneration, and by inference the DR status of the human hematopoietic stem cell.
D000328:Adult; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology; D006071:Gorilla gorilla / Q000276:immunology; D006684:HLA-DR Antigens; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D006922:Hylobates / Q000276:immunology; D008253:Macaca mulatta; D002679:Pan troglodytes / Q000276:immunology; D011148:Pongo pygmaeus / Q000276:immunology; D011323:Primates / Q000276:immunology*; D013045:Species Specificity
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D003165:Complement System Proteins