Lentiviral calnexin-modified dendritic cells promote expansion of high-avidity effector T cells with central memory phenotype.
Dendritic cells (DCs) are key immune mediators for the education and activation of effector cytotoxic T lymphocytes (CTLs). Ex vivo manipulation of DCs is an attractive strategy in immunotherapy. The chaperone proteins are known to hold the keys to proper protein folding and antigen processing. However, little is known of the role of molecular chaperones in DC and T-cell functions. We report that DCs expressing supraphysiological levels of calnexin, a chaperone protein, via lentiviral gene transfer stimulated the expansion of high-avidity CTLs with increased central memory phenotype. Microarray RNA profiling and analyses of protein expression with flow cytometry and multiplex enzyme-linked immunosorbent assay indicated that calnexin had a global effect on DCs with up-regulation of immune modulatory signals including costimulatory molecules, cytokines, chemokines and adhesion molecules. Compared with unmodified DCs, calnexin-DCs were capable of activating T cells to exhibit increased functional avidity associated with up-regulation of CCR7 and costimulatory tumour necrosis factor receptor superfamily molecules. These findings demonstrate a prominent role of calnexin in optimizing DC immunity with potential for improving immunotherapy.
Wang
Bei
B
Department of Molecular Genetics and Microbiology, University of Florida, College of Medicine, Gainesville, FL, USA.
Han
Shuhong
S
Lien
Lily
L
Chang
Lung-Ji
LJ
D000818:Animals; D000915:Antibody Affinity; D017951:Antigen Presentation / Q000276:immunology; D037281:Calnexin / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use; D049109:Cell Proliferation; D018920:Coculture Techniques; D003110:Colonic Neoplasms / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005822:Genetic Vectors; D007156:Immunologic Memory; D016130:Immunophenotyping; D016086:Lentivirus / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D054400:Receptors, CCR7 / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; C515371:Ccr7 protein, mouse; D054400:Receptors, CCR7; D037281:Calnexin
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