RRC ID 1517
著者 Sato K, Nakaoka T, Yamashita N, Yagita H, Kawasaki H, Morimoto C, Baba M, Matsuyama T.
タイトル TRAIL-transduced dendritic cells protect mice from acute graft-versus-host disease and leukemia relapse.
ジャーナル J Immunol
Abstract 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.
巻・号 174(7)
ページ 4025-33
公開日 2005-4-1
DOI 10.4049/jimmunol.174.7.4025
PII 174/7/4025
PMID 15778360
MeSH Acute Disease Animals Apoptosis / drug effects Apoptosis Regulatory Proteins Bone Marrow Transplantation / adverse effects CD4-Positive T-Lymphocytes / immunology Dendritic Cells / metabolism Genetic Therapy / methods* Graft vs Host Disease / prevention & control Graft vs Host Disease / therapy* Humans Leukemia / pathology Leukemia / therapy* Membrane Glycoproteins / administration & dosage Membrane Glycoproteins / pharmacology Membrane Glycoproteins / therapeutic use* Mice Mice, Inbred BALB C Secondary Prevention TNF-Related Apoptosis-Inducing Ligand Transduction, Genetic Tumor Necrosis Factor-alpha / administration & dosage Tumor Necrosis Factor-alpha / pharmacology Tumor Necrosis Factor-alpha / therapeutic use*
IF 4.886
引用数 31
WOS 分野 IMMUNOLOGY
リソース情報
ヒト・動物細胞 L929 P-815(RCB1167)