Mature dendritic cells induce tumor-specific type 1 regulatory T cells

Andreas Lundqvist, Andreas Palmborg, Maxim Pavlenko, Jelena Levitskaya, Pavel Pisa

Research output: Contribution to journalArticle

Abstract

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-α, 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-α, exhibited tumor antigen specificity, but accompanied by reduced proliferation and IFNγ 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.

Original languageEnglish (US)
Pages (from-to)229-235
Number of pages7
JournalJournal of Immunotherapy
Volume28
Issue number3
Publication statusPublished - May 2005
Externally publishedYes

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Keywords

  • Adenoviridae
  • Immunotherapy
  • Interleukin-10
  • Suppressor-effector
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

Cite this

Lundqvist, A., Palmborg, A., Pavlenko, M., Levitskaya, J., & Pisa, P. (2005). Mature dendritic cells induce tumor-specific type 1 regulatory T cells. Journal of Immunotherapy, 28(3), 229-235.