TRAIL-transduced dendritic cells protect mice from acute graft-versus-host disease and leukemia relapse.
TRAIL preferentially induces apoptotic cell death in a wide variety of transformed cells, whereas it induces no apoptosis, but inhibits activation of Ag-specific T cells via blockade of cell cycle progression. Although accumulating results suggest that TRAIL is involved in the maintenance of immunological homeostasis under steady state conditions as well as in the initiation and progression of immunopathologies, the potential regulatory effect of TRAIL on immune responses and its therapeutic potential in immunological diseases remains unclear. We report in this study the potential usefulness of TRAIL-transduced dendritic cells (DCs) for the treatment of lethal acute graft-vs-host disease (GVHD) and leukemia relapse. DCs genetically modified to express TRAIL showed potent cytotoxicity against both alloreactive T cells and leukemic cells through the induction of apoptosis. In addition, treatment with genetically modified DCs expressing TRAIL of allogeneic BM transplants recipients with leukemia was effective for protection against acute GVHD and leukemia relapse. Thus, gene transfer of TRAIL to DCs is a novel modality for the treatment of acute GVHD and leukemia relapse by selective targeting of pathogenic T cells and leukemic cells.
Sato
Katsuaki
K
Laboratory for Dendritic Cell Immunobiology, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Kanagawa, Japan. katsuaki@rcai.riken.jp
Nakaoka
Takashi
T
Yamashita
Naohide
N
Yagita
Hideo
H
Kawasaki
Hiroshi
H
Morimoto
Chikao
C
Baba
Masanori
M
Matsuyama
Takami
T
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006086:Graft vs Host Disease / Q000517:prevention & control / Q000628:therapy*; D006801:Humans; D007938:Leukemia / Q000473:pathology / Q000628:therapy*; D008562:Membrane Glycoproteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D055502:Secondary Prevention; D053221:TNF-Related Apoptosis-Inducing Ligand; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha