SEARCH

SEARCH BY CITATION

Keywords:

  • blood dendritic cell antigen-3 (BDCA-3);
  • interleukin-4 (IL-4);
  • plasmacytoid dendritic cell development;
  • T cell polarization;
  • T cell proliferation

To cite this article: Bratke K, Klein C, Kuepper M, Lommatzsch M, Christian Virchow J. Differential development of plasmacytoid dendritic cells in Th1- and Th2-like cytokine milieus. Allergy 2011; 66: 386–395.

Abstract

Background:  Plasmacytoid dendritic cells (pDCs) infiltrate sites of Th1- and Th2-dominant inflammation and many studies have been performed to analyse their role in these immune responses. In contrast, much less is known about the effects of a Th1 or Th2 cytokine milieu on pDC function. Therefore, we investigated the impact of Th1- and Th2-like conditions during the development of pDCs on their antigen expression and function.

Methods:  PDCs were matured in vitro by the addition of IL-3 under Th1- or Th2-like conditions. Antigen expression and TLR7-ligand-induced cytokine secretion was analysed by flow cytometry and ELISA. Furthermore, the CD4+ T-cell polarizing capacity of pDCs was determined as well as their potential to induce CD4+ T-cell proliferation.

Results:  PDCs matured under Th1-like conditions showed a higher expression of antigens involved in T-cell co-stimulation and antigen presentation like CD40, CD80, CD83 and HLA-DR as well as a higher secretion of IL-6 and IFN-α in response to TLR7-ligation compared to Th2-pDCs. Furthermore, Th1-pDCs induced a significantly higher CD4+ T-cell proliferation and primed a higher percentage of CD4+ T cells to express IFN-γ and IL-2 after TLR7-ligation compared to Th2-pDCs. In contrast, Th2-pDCs were characterized by a significant upregulation of BDCA-3 and IL-4 expression following TLR7-ligation.

Conclusion:  This study is the first to demonstrate the crucial impact of a surrounding cytokine environment on the development of pDC function including antigen expression. Based on these findings, it can be speculated that antiviral/bacterial pDC functions could be impaired during acute allergic conditions.