title: Effect of inflammation on costimulation blockade-resistant allograft rejection.
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.
authors.affiliation: Division of Immunobiology, Research Institute for Biological Sciences, Tokyo University of Science, Noda City, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Habiro
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimmura
authors.forename: Sakiko
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Motoko
authors.initials: M
authors.lastname: Kotani
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ishida
authors.forename: Kazunari
authors.initials: K
authors.lastname: Tanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Toma
authors.forename: Ryo
authors.initials: R
authors.lastname: Abe
mesh_terms: D000818:Animals; D018106:CD28 Antigens / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D018664:Interleukin-12 / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016038:Skin Transplantation; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D018106:CD28 Antigens; D019013:CD40 Antigens; D019409:Interleukin-15; D018664:Interleukin-12