Efficient Generation of Antigen-Specific Cytotoxic T Cells Using Retrovirally Transduced CD40-Activated B Cells

• DOI: 10.4049/jimmunol.169.4.2164
• Publication Date: 2014-04-20T22:19:11Z
• Authors: Eisei Kondo; Max S Topp; Hans-Peter Kiem; Yuichi Obata; Yasuo Morishima; Kiyotaka Kuzushima; Mitsune Tanimoto; Mine Harada; Toshitada Takahashi; Yoshiki Akatsuka
• Keywords: Antigen Presentation; B-Lymphocytes; CD40 Ligand; Phosphoproteins; 3. Good health; Viral Matrix Proteins; Epitopes; 03 medical and health sciences; 0302 clinical medicine; HLA Antigens; Transduction, Genetic; Leukemia Virus, Gibbon Ape; Cytomegalovirus Infections; Humans; Interleukin-4; CD40 Antigens; Antigens, Viral; Alleles; T-Lymphocytes, Cytotoxic

Abstract 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.