Efficient generation of antigen-specific cytotoxic T cells using retrovirally transduced CD40-activated B cells

被引:93
作者
Kondo, E
Topp, MS
Kiem, HP
Obata, Y
Morishima, Y
Kuzushima, K
Tanimoto, M
Harada, M
Takahashi, T
Akatsuka, Y
机构
[1] Aichi Canc Ctr Hosp, Div Immunol, Aichi Canc Ctr Res Inst, Nagoya, Aichi 464, Japan
[2] Aichi Canc Ctr Hosp, Dept Hematol & Chemotherapy, Nagoya, Aichi 464, Japan
[3] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA
[4] Univ Washington, Seattle, WA 98109 USA
[5] RIKEN, Dept Biol Syst, BioResources Ctr, Tsukuba Inst, Tsukuba, Ibaraki, Japan
[6] Okayama Univ, Sch Med, Dept Internal Med 2, Okayama 700, Japan
[7] Kyushu Univ, Dept Med & Biosystem Sci, Grad Sch Med Sci, Fukuoka 812, Japan
关键词
D O I
10.4049/jimmunol.169.4.2164
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The development of rapid, efficient, and safe methods for generating Ag-specific T cells is necessary for the clinical application of adoptive immunotherapy. We show that B cells stimulated with CD40 ligand and IL-4 (CD40-B cells) can be efficiently transduced with retroviral vectors encoding a model Ag, CMV tegument protein pp65 gene, and maintain high levels of costimulatory molecules after gene transfer. CTL lines specific for pp65 were readily generated in all four healthy CMV-seropositive donors by stimulating autologous CD8(+) T cells with these transduced CD40-B cells, both of which were derived from 10 ml peripheral blood. ELISPOT assays revealed that the CTL lines used multiple HLA alleles as restricting elements. Thus, CD40-B cells transduced retrovirally with Ag-encoding cDNA can be potent APC and facilitate to generate Ag-specific CTL in vitro.
引用
收藏
页码:2164 / 2171
页数:8
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