Human CD103+ dendritic cells promote the differentiation of Porphyromonas gingivalis heat shock protein peptidespecific regulatory T cells
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: Regulatory T cells (Tregs), expressing CD4 and CD25 as well as Foxp3, are knownto play a pivotal role in immunoregulatory function in autoimmune diseases, cancers, andgraft 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 fromprecursor human peripheral blood mononuclear cells (PBMCs). The aim of the present studywas to evaluate the capacity of these PBMC-derived CD103+ DCs to promote the differentiationof antigen-specific Tregs. Methods: Monocyte-derived DCs were induced from CD14+ monocytes from the PBMCs of10 healthy subjects. Once the CD103+ DCs were purified, the cell population was enrichedby adding retinoic acid (RA). Peptide numbers 14 and 19 of Porphyromonas gingivalis heatshock protein 60 (HSP60) were synthesized to pulse CD103+ DCs as a tool for presentingthe peptide antigens to stimulate CD3+ T cells that were isolated from human PBMC. Exogenousinterleukin 2 was added as a coculture supplement. The antigen-specific T-cell linesestablished were phenotypically identified for their expression of CD4, CD25, or Foxp3. Results: When PBMCs were used as APCs, they demonstrated only a marginal capacity tostimulate peptide-specific Tregs, whereas CD103+ DCs showed a potent antigen presentingcapability to promote the peptide-specific Tregs, especially for peptide 14. RA enhancedthe 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 fromnaive T cells, when used as APCs for an epitope peptide from P. gingivalis HSP60. RA wasan effective reagent that induces mature DCs with the typical phenotypic expression ofCD103 that demonstrated the functional capability to promote antigen-specific Tregs.
Abstract
Purpose: Regulatory T cells (Tregs), expressing CD4 and CD25 as well as Foxp3, are knownto play a pivotal role in immunoregulatory function in autoimmune diseases, cancers, andgraft 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 fromprecursor human peripheral blood mononuclear cells (PBMCs). The aim of the present studywas to evaluate the capacity of these PBMC-derived CD103+ DCs to promote the differentiationof antigen-specific Tregs. Methods: Monocyte-derived DCs were induced from CD14+ monocytes from the PBMCs of10 healthy subjects. Once the CD103+ DCs were purified, the cell population was enrichedby adding retinoic acid (RA). Peptide numbers 14 and 19 of Porphyromonas gingivalis heatshock protein 60 (HSP60) were synthesized to pulse CD103+ DCs as a tool for presentingthe peptide antigens to stimulate CD3+ T cells that were isolated from human PBMC. Exogenousinterleukin 2 was added as a coculture supplement. The antigen-specific T-cell linesestablished were phenotypically identified for their expression of CD4, CD25, or Foxp3. Results: When PBMCs were used as APCs, they demonstrated only a marginal capacity tostimulate peptide-specific Tregs, whereas CD103+ DCs showed a potent antigen presentingcapability to promote the peptide-specific Tregs, especially for peptide 14. RA enhancedthe 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 fromnaive T cells, when used as APCs for an epitope peptide from P. gingivalis HSP60. RA wasan effective reagent that induces mature DCs with the typical phenotypic expression ofCD103 that demonstrated the functional capability to promote antigen-specific Tregs.
참고문헌 (38)
- Tang Q, "The Foxp3+ regulatory T cell: a jack of all trades, master of regulation", Nat Immunol, 9, pp.239~244 (2008)
- Vignali DA, "How regulatory T cells work", Nat Rev Immunol, 8, pp.523~532 (2008)
- Guilliams M, "African trypanosomiasis: naturally occurring regulatory T cells favor trypanotolerance by limiting pathology associated with sustained type 1 inflammation", J Immunol, 179, pp.2748~2757 (2007)
- Groux H, "A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis", Nature, 389, pp.737~742 (1997)
- Fehervari Z, "CD4+ Tregs and immune control", J Clin Invest, 114, pp.1209~1217 (2004)
- Gambineri E, "Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis", Curr Opin Rheumatol, 15, pp.430~435 (2003)
- Viglietta V, "Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis", J Exp Med, 199, pp.971~979 (2004)
- Lindley S, "Defective suppressor function in CD4(+)CD25(+) T-cells from patients with type 1 diabetes", Diabetes, 54, pp.92~99 (2005)
- Ehrenstein MR, "Compromised function of regulatory T cells in rheumatoid arthritis and reversal by anti-TNFalpha therapy", J Exp Med, 200, pp.277~285 (2004)
- Brunkow ME, "Disruption of a new forkhead", winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouse, 2001, pp.27, 68~73
- Bennett CL, "The immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) is caused by mutations of FOXP3", Nat Genet, 27, pp.20~21 (2001)
- Wildin RS, "X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfy", Nat Genet, 27, pp.18~20 (2001)
- Fontenot JD, "Foxp3 programs the development and function of CD4+CD25+ regulatory T cells", Nat Immunol, 4, pp.330~336 (2003)
- Friedewald VE, "The American Journal of Cardiology and Journal of Periodontology editors' consensus: periodontitis and atherosclerotic cardiovascular disease", J Periodontol, 80, pp.1021~1032 (2009)
- Kebschull M, ""Gum bug, leave my heart alone!": epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis", J Dent Res, 89, pp.879~902 (2010)
- Wucherpfennig KW, "Structural basis of molecular mimicry", J Autoimmun, 16, pp.293~302 (2001)
- Rajaiah R, "Heat-shock proteins can promote as well as regulate autoimmunity", Autoimmun Rev, 8, pp.388~393 (2009)
- Wucherpfennig KW, "Mechanisms for the induction of autoimmunity by infectious agents", J Clin Invest, 108, pp.1097~1104 (2001)
- Delogu LG, "Infectious diseases and autoimmunity", J Infect Dev Ctries, 5, pp.679~687 (2011)
- Vanneman M, "Combining immunotherapy and targeted therapies in cancer treatment", Nat Rev Cancer, 12, pp.237~251 (2012)
- 최점일, "Vaccines against periodontitis: a forward-looking review", Journal of Periodontal & Implant Science, 40(4), pp.153~163 (2010), 대한치주과학회
- Banchereau J, "Immunobiology of dendritic cells", Annu Rev Immunol, 18, pp.767~811 (2000)
- Coombes JL, "A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism", J Exp Med, 204, pp.1757~1764 (2007)
- Sun CM, "Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid", J Exp Med, 204, pp.1775~1785 (2007)
- Chirdo FG, "Immunomodulatory dendritic cells in intestinal lamina propria", Eur J Immunol, 35, pp.1831~1840 (2005)
- Johansson C, "Phenotype and function of intestinal dendritic cells", Semin Immunol, 17, pp.284~294 (2005)
- Izcue A, "Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation", Immunol Rev, 212, pp.256~271 (2006)
- Annacker O, "Essential role for CD103 in the T cell-mediated regulation of experimental colitis", J Exp Med, 202, pp.1051~1061 (2005)
- Belkaid Y, "Regulatory T cells and infection: a dangerous necessity", Nat Rev Immunol, 7, pp.875~888 (2007)
- Van Eden W, "Stress, heat shock proteins, and autoimmunity: how immune responses to heat shock proteins are to be used for the control of chronic inflammatory diseases", Ann N Y Acad Sci, 1113, pp.217~237 (2007)
- Mills KH, "Antigen-specific regulatory T cells: their induction and role in infection", Semin Immunol, 16, pp.107~117 (2004)
- Yamazaki S, "Direct expansion of functional CD25+ CD4+ regulatory T cells by antigen-processing dendritic cells", J Exp Med, 198, pp.235~247 (2003)
- Lohr J, "Regulatory T cells in the periphery", Immunol Rev, 212, pp.149~162 (2006)
- Choi J, "Identification of immunoreactive epitopes of the Porphyromonas gingivalis heat shock protein in periodontitis and atherosclerosis", J Periodontal Res, 46, pp.240~245 (2011)
- Jeong E, "Porphyromonas gingivalis HSP60 peptides have distinct roles in the development of atherosclerosis", Mol Immunol (2014)
- Forsythe P, "Immunomodulation by commensal and probiotic bacteria", Immunol Invest, 39, pp.429~448 (2010)
- Hand T, "Microbial control of regulatory and effector T cell responses in the gut", Curr Opin Immunol, 22, pp.63~72 (2010)
- del Rio ML, "Development and functional specialization of CD103+ dendritic cells", Immunol Rev, 234, pp.268~281 (2010)