Effect of inflammation on costimulation blockade-resistant allograft rejection.
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.
Habiro
Katsuyoshi
K
Division of Immunobiology, Research Institute for Biological Sciences, Tokyo University of Science, Noda City, Japan.
Shimmura
Hiroaki
H
Kobayashi
Sakiko
S
Kotani
Motoko
M
Ishida
Yasuo
Y
Tanabe
Kazunari
K
Toma
Hiroshi
H
Abe
Ryo
R
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
D018106:CD28 Antigens; D019013:CD40 Antigens; D019409:Interleukin-15; D018664:Interleukin-12