Graft vs. host disease (GVHD) represents the major obstacle to more widespread clinical application of allogeneic hematopoietic cell transplants and experimentally provides perhaps the most important model for immunologists to study the significance and regulation of allogeneic T cell responses in situ. The sensitivity of induction to donor T cell numbers, the target tissues attacked in the host and the clinical sequelae associated with the pathogenesis of GVHD in the mouse remarkably parallel that which occurs in humans and thus has provided an extremely useful tool to dissect the underlying cells and mechanisms involved in this complex disorder. This review describes the general features of GVHD followed by a description of the three stages which define this response. Approaches being developed to regulate experimental as well as clinical GVHD during these different stages are then discussed. We conclude that advances towards the targeting of each stage of the process are raising hope that clinicians will one day be able to control both the light and dark sides of GVHD. The challenge to refine and implement such approaches at the bedside necessitates continued interactions and collaborative efforts between laboratories dedicated to applying the underlying cellular and molecular biology of hematolymphoid cells to transplantation together with clinician scientists motivated by the goal to perform hematopoietic cell transplants without fear of complications.
Keywords: lymphohematopoeitic compartment, effector T cells, malignancy, host anti-donor (HVG), knockout mice, Inducible costimulator (ICOS), sphingosine-1-phosphate receptor agonist
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