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) |