Cells with dendritic cell morphology and immunophenotype, binuclear morphology, and immunosuppressive function in

Rong Dong1, Dale Moulding, Nourredine Himoudi

  • 1Unit of Molecular Haematology and Cancer Biology, UCL Institute of Child Health, London, UK.

Cellular Immunology
|October 28, 2011
PubMed

Insights

Binuclear cells in dendritic cell (DC) cultures, termed BNiDCs, arise from cell fusion events. These cells exhibit tolerogenic properties, potentially impacting clinical vaccine development.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Dendritic cells (DCs) are generated from CD14 positive monocytes for research and clinical vaccines.
  • Binuclear cells (BNiDCs) with typical DC morphology were unexpectedly observed in human DC cultures.

Purpose of the Study:

  • To investigate the origin and functional characteristics of binuclear cells (BNiDCs) in human dendritic cell cultures.
  • To determine the impact of BNiDCs on immune responses and their role in clinical applications.

Main Methods:

  • Single cell PCR analysis of mitochondrial DNA polymorphisms to detect cell fusion.
  • Flow cytometry to analyze immunophenotype (HLA-DR, IL-12p70, IL-10).
  • Mixed lymphocyte reactions (MLRs) to assess BNiDC function.
  • Inhibition of dendritic cell-specific transmembrane protein (DC-STAMP) to study BNiDC formation.

Main Results:

  • Approximately 20-25% of cells in DC cultures undergo fusion, resulting in BNiDCs.
  • BNiDCs express low HLA-DR and IL-12p70, but high IL-10 levels.
  • Purified BNiDCs suppressed lymphocyte proliferation in MLRs.
  • Blocking DC-STAMP reduced the incidence of BNiDCs.

Conclusions:

  • BNiDCs are a fusion-derived population within human DC cultures.
  • BNiDCs possess tolerogenic properties, characterized by IL-10 production and suppression of lymphocyte proliferation.
  • The formation of BNiDCs can be influenced by DC-STAMP.
  • BNiDCs may represent a significant tolerogenic cell population in clinical DC preparations.