title: Transplantation of CD6-depleted peripheral blood stem cells after DLA-haploidentical bone marrow transplantation contributes to engraftment and tolerance in a preclinical model of stem cell transplantation.
abstract: Human leukocyte antigen (HLA)-haploidentical stem cell transplantation is an opportunity for nearly all patients lacking an HLA matched stem cell donor. However, graft rejection and graft-versus-host disease (GvHD) as well as infectious complications still result in high treatment-related mortality. Here, we used the dog as a preclinical model for the study of tolerance induction with the aim to optimize and to improve a clinical protocol of haploidentical stem cell transplantation. For this purpose CD6-depleted peripheral blood stem cells (PBSCs) were transfused 6d after transplantation of unmodified bone marrow from dog leukocyte antigen (DLA)-haploidentical littermate donors in order to induce immune tolerance. Besides hematopoietic stem cells CD6-depleted PBSC contain, NK cells and a minority of suppressive CD8-positive cells that may suppress activated T lymphocytes. Recipients were conditioned with, cyclophosphamide and antithymocyte globulin (ATG) preceded by a transfusion of donor buffy coat and either 1, 2 or 3 × 3.3 Gy total body irradiation (TBI). Postgrafting immunosuppression was limited to 30 d of cyclosporine and methotrexate. The additional administration of CD6-depleted PBSCs after unmodified marrow could not prevent GvHD, but it may improve engraftment and chimerism after conditioning with 2 × 3.3 Gy TBI. Reasons for incomplete suppression and possible improvements for clinical applications are discussed.
authors.affiliation: Helmholtz Zentrum München - National Research Center for Environmental Health, Institute of Molecular Immunology, Clinical Cooperation Group Hematopoietic Cell Transplantation, Marchioninistrasse 25, D-81377 Munich, Germany. julia.zorn@helmholtz-muenchen.de
authors.forename: Julia
authors.initials: J
authors.lastname: Zorn
authors.forename: Sabine
authors.initials: S
authors.lastname: Schwamberger
authors.forename: Werner
authors.initials: W
authors.lastname: Panzer
authors.forename: Heiko
authors.initials: H
authors.lastname: Adler
authors.forename: Hans-Jochem
authors.initials: HJ
authors.lastname: Kolb
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000379:methods / Q000662:veterinary*; D046528:Chimerism / Q000662:veterinary; D003114:Colony-Forming Units Assay / Q000662:veterinary; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000662:veterinary*; D008297:Male
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen