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

Julia Zorn, Sabine Schwamberger, Werner Panzer, Heiko Adler, Hans Jochem Kolb

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 6. d 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.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalVeterinary Immunology and Immunopathology
Volume144
Issue number1-2
DOIs
StatePublished - 15 Nov 2011
Externally publishedYes

Keywords

  • Animal model
  • CD6-depletion
  • Dog
  • GvHD
  • Haploidentical stem cell transplantation
  • Tolerance

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