Human CD103+ dendritic cells promote the differentiation of Porphyromonas gingivalis heat shock protein peptide-specific regulatory T cells
김명진, 정의경, 권은영, 주지영, 이주연, 최점일,
소속 상세정보
김명진 ( Kim Myung-Jin ) - Pusan National University College of Dentistry Department of Periodontology
정의경 ( Jeong Eui-Kyong ) - Pusan University College of Natural Sciences Department of Molecular Biology
권은영 ( Kwon Eun-Young ) - Pusan National University School of Dentistry Department of Periodontology
주지영 ( Joo Ji-Young ) - Pusan National University School of Dentistry Department of Periodontology
이주연 ( Lee Ju-Youn ) - Pusan National University School of Dentistry Department of Periodontology
최점일 ( Choi Jeom-Il ) - Pusan National University College of Dentistry Department of Periodontology
KMID : 0363020140440050235
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.
키워드
Autoimmune diseases; Cells; Immunity; Periodontitis; Proteins
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