Eva Guinan, Leo Luzmik, Rupert Handgretinger, Ann Woolfrey

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Presentation transcript:

Preservation of Immune Repertoire by Selective Depletion of Haploidentical Grafts Eva Guinan, Leo Luzmik, Rupert Handgretinger, Ann Woolfrey Biology of Blood and Marrow Transplantation Volume 16, Issue 1, Pages S68-S74 (January 2010) DOI: 10.1016/j.bbmt.2009.11.015 Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Activated T cells are relatively more sensitive to the effects of cyclophosphamide compared to resting T cells. Following nonmyeloablative conditioning, both donor and host T cells are exposed to alloantigens, resulting in activation and proliferation of T cells capable of host-versus-graft and graft-versus-host reactions. Expansion of the alloreactive clones occurs in the first 3 days after transplant, at which point cyclophosphamide is given to deplete activated T cells. Hematopoietic stem cells and resting T cells are relatively resistant to cyclophosphamide, which preserves T cells that recognize viral antigens and enhances immune reconstitution. Biology of Blood and Marrow Transplantation 2010 16, S68-S74DOI: (10.1016/j.bbmt.2009.11.015) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Flow cytometric analysis of CD34+ positively selected stem cells and CD3/19 negatively depleted PBSCs. Although the CD34+ population is homogenous without any contaminating non-T/B-cells, the CD3/19 depleted PBSC's contain large numbers of non- T/B-cells, including CD34+ stem cells, NK cells, and myeloid cells. Biology of Blood and Marrow Transplantation 2010 16, S68-S74DOI: (10.1016/j.bbmt.2009.11.015) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 The NK activity of PBSCs without and with overnight stimulation with IL-2 and IL-15 against the standard target cell line K562 is shown. Biology of Blood and Marrow Transplantation 2010 16, S68-S74DOI: (10.1016/j.bbmt.2009.11.015) Copyright © 2010 American Society for Blood and Marrow Transplantation Terms and Conditions