title: Human CD103(+) dendritic cells promote the differentiation of Porphyromonas gingivalis heat shock protein peptide-specific regulatory T cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Periodontology, Pusan University School of Dentistry, Yangsan, Korea.
authors.forename: Myung-Jin
authors.identifier: 0000-0003-0528-6848
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Molecular Biology, Pusan University College of Natural Sciences, Yangsan, Korea.
authors.forename: Eui-Kyong
authors.identifier: 0000-0001-9866-9842
authors.initials: EK
authors.lastname: Jeong
authors.affiliation: Department of Periodontology, Pusan University School of Dentistry, Yangsan, Korea.
authors.forename: Eun-Young
authors.identifier: 0000-0001-9555-0360
authors.initials: EY
authors.lastname: Kwon
authors.affiliation: Department of Periodontology, Pusan University School of Dentistry, Yangsan, Korea.
authors.forename: Ji-Young
authors.identifier: 0000-0002-4050-5797
authors.initials: JY
authors.lastname: Joo
authors.affiliation: Department of Periodontology, Pusan University School of Dentistry, Yangsan, Korea.
authors.forename: Ju-Youn
authors.identifier: 0000-0002-0772-033X
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Periodontology, Pusan University School of Dentistry, Yangsan, Korea.
authors.forename: Jeomil
authors.identifier: 0000-0002-7491-6711
authors.initials: J
authors.lastname: Choi
keywords: Autoimmune diseases; Cells; Immunity; Periodontitis; Proteins