Effect of Inflammation on Costimulation Blockade-Resistant Allograft Rejection |
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Authors: | Katsuyoshi Habiro Hiroaki Shimmura Sakiko Kobayashi Motoko Kotani Yasuo Ishida Kazunari Tanabe Hiroshi Toma Ryo Abe |
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Affiliation: | Division of Immunobiology, Research Institute for Biological Sciences, Tokyo University of Science, Noda City, Japan;Department of Urology, Tokyo Women's Medical University, Tokyo, Japan;Department of Surgical Pathology, Teikyo University, School of Medicine, Ichihara Hospital, Ichihara City, Japan;Genome and Drug Research Center, Tokyo University of Science, Noda City, Japan |
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Abstract: | Previously, we reported that allogeneic skin grafts were rapidly rejected by CD28 and CD40 ligand double deficient mice mediated by CD8+ T cells. These results indicated that some elements in addition to CD28- and CD40-mediated costimulation provide stimulatory signals for the activation of donor-specific CD8+ T cells. In this report, we investigated the role of inflammation associated with transplantation on costimulation-independent priming of CD8+ T cell during graft rejection. B6 RAG1 KO mice were transplanted with BALB/c-skin and adoptively transferred with syngeneic CD8+ T cells the same day or 50 days after transplantation. When blockade of CD28- and CD40-mediated costimulation failed to prevent acute rejection of freshly transplanted skin grafts, it efficiently delayed rejection of well-healed skin grafts. These results showed that factors associated with transplantation have essential roles in inducing costimulation blockade-resistant allograft rejection. Costimulation blockade failed to prevent acute graft-infiltration of NK cells and increasing expression of intragraft IL-12 and IL-15. These factors may trigger the graft-infiltration and priming of CD8+ T cells to induce costimulation blockade-resistant allograft rejection. |
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Keywords: | CD8+ T cell costimulation blockade IL-12 IL-15 inflammation NK cell skingraft transplantation |
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