Cytolytic Pathways Used by Effector Cells Derived from Recipient Naive and Memory T Cells and Natural Killer Cells in Resistance to Allogeneic Hematopoietic.

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Presentation transcript:

Cytolytic Pathways Used by Effector Cells Derived from Recipient Naive and Memory T Cells and Natural Killer Cells in Resistance to Allogeneic Hematopoietic Cell Transplantation Zachary Zimmerman, Monica Jones, Alwi Shatry, Masanobu Komatsu, Michele Mammolenti, Robert Levy Biology of Blood and Marrow Transplantation Volume 11, Issue 12, Pages 957-971 (December 2005) DOI: 10.1016/j.bbmt.2005.07.006 Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Summary of parameters that affect the outcome of engraftment after allogeneic hematopoietic cell transplantation. Factors such as the nature of pretransplantation conditioning, prior sensitization to donor alloantigen, and the genetic disparity between the donor and the recipient can affect the cellular constituency of the host immune barrier to alloengraftment. This barrier could be mediated by the induction of apoptosis or other effector pathways. Ab indicates antibody; PC, progenitor cell. Biology of Blood and Marrow Transplantation 2005 11, 957-971DOI: (10.1016/j.bbmt.2005.07.006) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 Lytic pathways that could contribute to resistance against allogeneic hematopoietic stem/progenitor cells. The primary cell-mediated lytic pathways (ie, perforin/granzyme and fasL-fas), as well as recently discovered death ligand/receptor pairs that could be expressed by effector and progenitor cells. Biology of Blood and Marrow Transplantation 2005 11, 957-971DOI: (10.1016/j.bbmt.2005.07.006) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 Potential barrier composition in women after allogeneic HSPCT. Depending on the genetic disparity between donor and recipient and the potential presence of anti-donor reactive T memory cells, the cellular constituency of the immune-mediated barrier to alloengraftment may be composed of multiple cell populations in the recipient. For example, sensitization to paternally derived alloantigens during pregnancy is one setting in which anti-donor alloantigen-reactive memory T cells could be generated. Biology of Blood and Marrow Transplantation 2005 11, 957-971DOI: (10.1016/j.bbmt.2005.07.006) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 A proposed model for the involvement of cytotoxic effector pathways in immune-mediated resistance to allogeneic hematopoietic stem/progenitor cell engraftment. The model presents the hypothesis that depending on the source of the effector cells that are generated in recipients after transplantation, the contribution of cytotoxic pathways will differ. For example, if effector cells are derived from naive host CD8+ T cells (or NK cells), cytolytic activity via perforin- or fasL-dependent pathways is critical for generation of a strong barrier to engraftment. In contrast, effector cells derived from host CD8+ memory T cells mediate potent barrier activity independently of these 2 pathways. Biology of Blood and Marrow Transplantation 2005 11, 957-971DOI: (10.1016/j.bbmt.2005.07.006) Copyright © 2005 American Society for Blood and Marrow Transplantation Terms and Conditions