title: Interferon-α abrogates tolerance induction by human tolerogenic dendritic cells.
abstract: BACKGROUND
  Administration of interferon-α (IFN-α) represents an approved adjuvant therapy as reported for malignancies like melanoma and several viral infections. In malignant diseases, tolerance processes are critically involved in tumor progression. In this study, the effect of IFN-α on tolerance induction by human tolerogenic dendritic cells (DC) was analyzed. We focussed on tolerogenic IL-10-modulated DC (IL-10 DC) that are known to induce anergic regulatory T cells (iTregs).
  
  
  RESULTS
  IFN-α promoted an enhanced maturation of IL-10 DC as demonstrated by upregulation of the differentiation marker CD83 as well as costimulatory molecules. IFN-α treatment resulted in an increased capacity of DC to stimulate T cell activation compared to control tolerogenic DC. We observed a strengthened T cell proliferation and increased IFN-γ production of CD4(+) and CD8(+) T cells stimulated by IFN-α-DC, demonstrating a restoration of the immunogenic capacity of tolerogenic DC in the presence of IFN-α. Notably, restimulation experiments revealed that IFN-α treatment of tolerogenic DC abolished the induction of T cell anergy and suppressor function of iTregs. In contrast, IFN-α neither affected the priming of iTregs nor converted iTregs into effector T cells.
  
  
  CONCLUSIONS
  IFN-α inhibits the induction of T cell tolerance by reversing the tolerogenic function of human DC.
authors.affiliation: Department of Dermatology, University Medical Center Mainz, University of Mainz, Mainz, Germany. nicole.bacher@unimedizin-mainz.de
authors.forename: Nicole
authors.initials: N
authors.lastname: Bacher
authors.forename: Edith
authors.initials: E
authors.lastname: Graulich
authors.forename: Helmut
authors.initials: H
authors.lastname: Jonuleit
authors.forename: Stephan
authors.initials: S
authors.lastname: Grabbe
authors.forename: Kerstin
authors.initials: K
authors.lastname: Steinbrink
mesh_terms: D002454:Cell Differentiation / Q000276:immunology; D017635:Clonal Anergy / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D007114:Immunization; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000494:pharmacology*; D016753:Interleukin-10 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D016898:Interferon-alpha; D016753:Interleukin-10