Mature dendritic cells induce tumor-specific type 1 regulatory T cells.
The aim of this study was to compare the tumor antigen-specific T-cell repertoire generated by transduced, human dendritic cells (DCs). The transductions were three commonly used antigen delivery procedures: adenovirus (AdV) infection, RNA electroporation, and liposome-mediated protein transfection. The DCs in each experimental group were transfected with similar efficacy and matured using TNF-alpha, anti-CD40, or lipopolysaccharide. Regardless of the gene transfer method or the maturation stimuli used, the DCs were indistinguishable with regard to surface phenotype and allostimulatory capacity. With the exception of the Adv transduced group, the T cells generated were tumor antigen specific, as characterized by high IFN-gamma production. The T cells generated upon stimulation with DCs subjected to AdV infection, and subsequently treated with TNF-alpha, exhibited tumor antigen specificity, but accompanied by reduced proliferation and IFNgamma production and increased IL-10 production. Moreover, these T cells exerted a suppressive effect on both autologous and allogeneic lymphocytes resembling type 1 regulatory T cells (Tr1). The authors show that mature DCs may induce tumor antigen-specific Tr1 cells by the appearance of high IL-10 and low IL-12. Similar results were also obtained with AdV-infected and TNF-matured DCs regardless of the transgene used. This work supports the conclusion that it can no longer be assumed that mature DCs induce only antitumor reactive T cells.
Lundqvist
Andreas
A
Cancer Center Karolinska, Immune and Gene Therapy, Department of Oncology and Pathology, Karolinska Institute, S-17176 Stockholm, Sweden.
Palmborg
Andreas
A
Pavlenko
Maxim
M
Levitskaya
Jelena
J
Pisa
Pavel
P
D000256:Adenoviridae / Q000235:genetics; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000951:Antigens, Neoplasm; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D017430:Prostate-Specific Antigen