PMID- 21784536 OWN - NLM STAT- MEDLINE DCOM- 20120217 LR - 20111024 IS - 1873-2534 (Electronic) IS - 0165-2427 (Linking) VI - 144 IP - 1-2 DP - 2011 Nov 15 TI - 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. PG - 27-35 LID - 10.1016/j.vetimm.2011.06.036 [doi] AB - 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 x 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 x 3.3 Gy TBI. Reasons for incomplete suppression and possible improvements for clinical applications are discussed. CI - Copyright (c) 2011 Elsevier B.V. All rights reserved. FAU - Zorn, Julia AU - Zorn J AD - Helmholtz Zentrum Munchen - 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 FAU - Schwamberger, Sabine AU - Schwamberger S FAU - Panzer, Werner AU - Panzer W FAU - Adler, Heiko AU - Adler H FAU - Kolb, Hans-Jochem AU - Kolb HJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110702 PL - Netherlands TA - Vet Immunol Immunopathol JT - Veterinary immunology and immunopathology JID - 8002006 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, T-Lymphocyte) RN - 0 (CD6 antigen) SB - IM MH - Animals MH - Antigens, CD/immunology MH - Antigens, Differentiation, T-Lymphocyte/immunology MH - Bone Marrow Transplantation/methods/*veterinary MH - Chimerism/veterinary MH - Colony-Forming Units Assay/veterinary MH - Disease Models, Animal MH - Dogs MH - Female MH - Graft vs Host Disease/immunology/prevention & control/veterinary MH - Hematopoietic Stem Cell Transplantation/methods/*veterinary MH - Male EDAT- 2011/07/26 06:00 MHDA- 2012/02/18 06:00 CRDT- 2011/07/26 06:00 PHST- 2011/02/15 00:00 [received] PHST- 2011/06/05 00:00 [revised] PHST- 2011/06/27 00:00 [accepted] PHST- 2011/07/26 06:00 [entrez] PHST- 2011/07/26 06:00 [pubmed] PHST- 2012/02/18 06:00 [medline] AID - S0165-2427(11)00234-0 [pii] AID - 10.1016/j.vetimm.2011.06.036 [doi] PST - ppublish SO - Vet Immunol Immunopathol. 2011 Nov 15;144(1-2):27-35. doi: 10.1016/j.vetimm.2011.06.036. Epub 2011 Jul 2.