Prolonged allogeneic and xenogeneic microchimerism in unmatched primates without immunosuppression by intrathymic implantation of CD34+ donor marrow cells.
Engraftment of stem cell-enriched donor marrow implanted in the thymus of a foreign host might facilitate acceptance of donor-specific organ or tissue grafts. To test this hypothesis, allogeneic and xenogeneic CD34+ marrow cells from unrelated adult male baboons and humans were injected intrathymically in eight infant female baboons, both with and without standard cyclosporine-based immunosuppression. In allogeneic experiments, male (donor) cells, of both T- and B-cell lineages, were detected by PCR in the peripheral blood of all six recipients and persisted for at least 15 months in 2/4 recipients studied longtutudinally. Donor-derived skin grafts survived twice as long as third party grafts in unimmunosuppressed recipients. In xenogeneic protocols, human male (donor) cells were demonstrable for 7 and 15 months, respectively, in two baboon recipients with evidence that implanted human CD34+ cells had produced lymphoid progeny. Survival of donor-specific skin xenografts was prolonged in one of two recipients. These experiments demonstrate that the intrathymic injection of CD34+ marrow cells can result in long-lasting lymphohematopoietic microchimerism in unrelated primates even without immunosuppression and can alter donor-specific skin graft survival.
Allen
M D
MD
Department of Surgery, University of Washington, Seattle, USA.
Weyhrich
J
J
Gaur
L
L
Akimoto
H
H
Hall
J
J
Dalesandro
J
J
Sai
S
S
Thomas
R
R
Nelson
K A
KA
Andrews
R G
RG
D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells / Q000276:immunology; D016026:Bone Marrow Transplantation; D002678:Chimera; D005260:Female; D006082:Graft Enhancement, Immunologic; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007518:Isoantibodies / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D010215:Papio; D016038:Skin Transplantation / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology*; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
D018952:Antigens, CD34; D007074:Immunoglobulin G; D007518:Isoantibodies