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CpG-matured murine plasmacytoid dendritic cells are capable of in vivo priming of functional CD8 T cell responses to endogenous but not exogenous antigens.

Salio M, Palmowski MJ, Atzberger A, Hermans IF, Cerundolo V - J. Exp. Med. (2004)

Bottom Line: In vitro experiments have shown that upon maturation, human and murine PDCs develop into potent immunostimulatory cells; however, their ability to prime an immune response in vivo remains to be addressed.In contrast, immature PDCs are unable to prime antigen-specific CTLs.Our results underline the heterogeneity and plasticity of different antigen-presenting cells, and reveal an important role of mature PDCs in priming CD8 responses to endogenous antigens, in addition to their previously reported ability to modulate antiviral responses via type I IFN.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Tumor Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headley Way, OX3 9DS Oxford, UK. mariolina.salio@imm.ox.ac.uk

ABSTRACT
Plasmacytoid dendritic cells (PDCs) are a unique leukocyte population capable of secreting high levels of type I interferon (IFN) in response to viruses and bacterial stimuli. In vitro experiments have shown that upon maturation, human and murine PDCs develop into potent immunostimulatory cells; however, their ability to prime an immune response in vivo remains to be addressed. We report that CpG-matured murine PDCs are capable of eliciting in naive mice antigen-specific CTLs against endogenous antigens as well as exogenous peptides, but not against an exogenous antigen. Type I IFN is not required for priming, as injection of CpG-matured PDCs into type I IFN receptor-deficient mice elicits functional CTL responses. Mature PDCs prime CTLs that secrete IFN-gamma and protect mice from a tumor challenge. In contrast, immature PDCs are unable to prime antigen-specific CTLs. However, mice injected with immature PDCs are fully responsive to secondary antigenic challenges, suggesting that PDCs have not induced long-lasting tolerance via anergic or regulatory T cells. Our results underline the heterogeneity and plasticity of different antigen-presenting cells, and reveal an important role of mature PDCs in priming CD8 responses to endogenous antigens, in addition to their previously reported ability to modulate antiviral responses via type I IFN.

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Intravenous injection of CpG-matured male PDCs induces IFN-γ–secreting CTL. C57BL/6 mice (n = 5) were primed as described in Fig. 1. ELISPOT assay was performed on blood PBLs to assess IFN-γ secretion by antigen-specific cells in response to 10 μg/ml UTY246–254 peptide 7 d after priming. All animals showed comparable responses to PHA stimulation (not depicted).
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fig3: Intravenous injection of CpG-matured male PDCs induces IFN-γ–secreting CTL. C57BL/6 mice (n = 5) were primed as described in Fig. 1. ELISPOT assay was performed on blood PBLs to assess IFN-γ secretion by antigen-specific cells in response to 10 μg/ml UTY246–254 peptide 7 d after priming. All animals showed comparable responses to PHA stimulation (not depicted).

Mentions: ELISPOT assays were performed to assess the capacity of UTY246–254-specific CTLs to secrete IFN-γ in response to peptide stimulation. As shown in Fig. 3, and in agreement with the tetramer data, mice primed by either mature PDCs or immature and mature MDCs were capable of recognizing the UTY246–254 peptide in an ex vivo assay, without further in vitro restimulation. No specific IFN-γ secretion was observed in mice primed by immature PDCs.


CpG-matured murine plasmacytoid dendritic cells are capable of in vivo priming of functional CD8 T cell responses to endogenous but not exogenous antigens.

Salio M, Palmowski MJ, Atzberger A, Hermans IF, Cerundolo V - J. Exp. Med. (2004)

Intravenous injection of CpG-matured male PDCs induces IFN-γ–secreting CTL. C57BL/6 mice (n = 5) were primed as described in Fig. 1. ELISPOT assay was performed on blood PBLs to assess IFN-γ secretion by antigen-specific cells in response to 10 μg/ml UTY246–254 peptide 7 d after priming. All animals showed comparable responses to PHA stimulation (not depicted).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211835&req=5

fig3: Intravenous injection of CpG-matured male PDCs induces IFN-γ–secreting CTL. C57BL/6 mice (n = 5) were primed as described in Fig. 1. ELISPOT assay was performed on blood PBLs to assess IFN-γ secretion by antigen-specific cells in response to 10 μg/ml UTY246–254 peptide 7 d after priming. All animals showed comparable responses to PHA stimulation (not depicted).
Mentions: ELISPOT assays were performed to assess the capacity of UTY246–254-specific CTLs to secrete IFN-γ in response to peptide stimulation. As shown in Fig. 3, and in agreement with the tetramer data, mice primed by either mature PDCs or immature and mature MDCs were capable of recognizing the UTY246–254 peptide in an ex vivo assay, without further in vitro restimulation. No specific IFN-γ secretion was observed in mice primed by immature PDCs.

Bottom Line: In vitro experiments have shown that upon maturation, human and murine PDCs develop into potent immunostimulatory cells; however, their ability to prime an immune response in vivo remains to be addressed.In contrast, immature PDCs are unable to prime antigen-specific CTLs.Our results underline the heterogeneity and plasticity of different antigen-presenting cells, and reveal an important role of mature PDCs in priming CD8 responses to endogenous antigens, in addition to their previously reported ability to modulate antiviral responses via type I IFN.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Tumor Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headley Way, OX3 9DS Oxford, UK. mariolina.salio@imm.ox.ac.uk

ABSTRACT
Plasmacytoid dendritic cells (PDCs) are a unique leukocyte population capable of secreting high levels of type I interferon (IFN) in response to viruses and bacterial stimuli. In vitro experiments have shown that upon maturation, human and murine PDCs develop into potent immunostimulatory cells; however, their ability to prime an immune response in vivo remains to be addressed. We report that CpG-matured murine PDCs are capable of eliciting in naive mice antigen-specific CTLs against endogenous antigens as well as exogenous peptides, but not against an exogenous antigen. Type I IFN is not required for priming, as injection of CpG-matured PDCs into type I IFN receptor-deficient mice elicits functional CTL responses. Mature PDCs prime CTLs that secrete IFN-gamma and protect mice from a tumor challenge. In contrast, immature PDCs are unable to prime antigen-specific CTLs. However, mice injected with immature PDCs are fully responsive to secondary antigenic challenges, suggesting that PDCs have not induced long-lasting tolerance via anergic or regulatory T cells. Our results underline the heterogeneity and plasticity of different antigen-presenting cells, and reveal an important role of mature PDCs in priming CD8 responses to endogenous antigens, in addition to their previously reported ability to modulate antiviral responses via type I IFN.

Show MeSH
Related in: MedlinePlus