Since its description roughly 30 years ago, the parent-into-F1 model of graft-vs.-host disease has provided insights into the mechanisms of in vivo T cell activation and the pathogenesis of autoimmune conditions. A new and emerging role for the P-->F1 model is one of identifying agents with immunomodulatory activity and defining in vivo mechanisms that promote cell mediated or antibody mediated immune responses. Because F1 mice are not irradiated prior to donor cell transfer, the P-->F1 model has in the past not been strictly analogous to human hematopoetic stem cell transplantation. However with the advent of newer non-myeloablative conditioning regimens, the model may assume more relevance. In this article, we first provide a review of relevant earlier fundamental observations followed by a summary of recent work from our laboratory in which acute and chronic GVHD in this model have been used not only to study normal T cell responses in vivo but also to define mechanisms important in the pathogenesis of autoimmunity and immunomodulation.
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