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Human $CD103^+$ dendritic cells promote the differentiation of Porphyromonas gingivalis heat shock protein peptide-specific regulatory T cells

  • Kim, Myung-Jin (Department of Periodontology, Pusan University School of Dentistry) ;
  • Jeong, Eui-Kyong (Department of Molecular Biology, Pusan University College of Natural Sciences) ;
  • Kwon, Eun-Young (Department of Periodontology, Pusan University School of Dentistry) ;
  • Joo, Ji-Young (Department of Periodontology, Pusan University School of Dentistry) ;
  • Lee, Ju-Youn (Department of Periodontology, Pusan University School of Dentistry) ;
  • Choi, Jeomil (Department of Periodontology, Pusan University School of Dentistry)
  • Received : 2014.07.26
  • Accepted : 2014.09.24
  • Published : 2014.10.31

Abstract

Purpose: Regulatory T cells (Tregs), expressing CD4 and CD25 as well as Foxp3, are known to play a pivotal role in immunoregulatory function in autoimmune diseases, cancers, and graft rejection. Dendritic cells (DCs) are considered the major antigen-presenting cells (APCs) for initiating these T-cell immune responses, of which $CD103^+$ DCs are derived from precursor human peripheral blood mononuclear cells (PBMCs). The aim of the present study was to evaluate the capacity of these PBMC-derived $CD103^+$ DCs to promote the differentiation of antigen-specific Tregs. Methods: Monocyte-derived DCs were induced from $CD14^+$ monocytes from the PBMCs of 10 healthy subjects. Once the $CD103^+$ DCs were purified, the cell population was enriched by adding retinoic acid (RA). Peptide numbers 14 and 19 of Porphyromonas gingivalis heat shock protein 60 (HSP60) were synthesized to pulse $CD103^+$ DCs as a tool for presenting the peptide antigens to stimulate $CD3^+$ T cells that were isolated from human PBMC. Exogenous interleukin 2 was added as a coculture supplement. The antigen-specific T-cell lines established were phenotypically identified for their expression of CD4, CD25, or Foxp3. Results: When PBMCs were used as APCs, they demonstrated only a marginal capacity to stimulate peptide-specific Tregs, whereas $CD103^+$ DCs showed a potent antigen presenting capability to promote the peptide-specific Tregs, especially for peptide 14. RA enhanced the conversion of $CD103^+$ DCs, which paralleled the antigen-specific Treg-stimulating effect, though the differences failed to reach statistical significance. Conclusions: We demonstrated that $CD103^+$ DCs can promote antigen-specific Tregs from naive T cells, when used as APCs for an epitope peptide from P. gingivalis HSP60. RA was an effective reagent that induces mature DCs with the typical phenotypic expression of CD103 that demonstrated the functional capability to promote antigen-specific Tregs.

Keywords

References

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