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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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Related in: MedlinePlus

Priming by CpG-matured PDCs induces protective CTL responses. C57BL/6 mice (n = 5) were primed by intravenous injection of 2 × 105 immature or CpG-matured MDC or PDCs pulsed with 1 μg/ml LCMV gp34–41 peptide. Control animals were injected with unpulsed CpG-DCs. (A) CTL responses were assessed in the blood by FACS® analysis using LCMV gp34–41-H-2-Kb tetramers 7 d after priming. Mean proportions of tetramer+ cells as a percentage of CD8 cells (± SEM) for each group are shown. (B) Progression of B16-F10-gp33 tumors implanted s.c. 10 d after priming. Mean tumor sizes per group ± SEM are shown. An additional control group (n = 5) that did not receive DCs was included.
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fig9: Priming by CpG-matured PDCs induces protective CTL responses. C57BL/6 mice (n = 5) were primed by intravenous injection of 2 × 105 immature or CpG-matured MDC or PDCs pulsed with 1 μg/ml LCMV gp34–41 peptide. Control animals were injected with unpulsed CpG-DCs. (A) CTL responses were assessed in the blood by FACS® analysis using LCMV gp34–41-H-2-Kb tetramers 7 d after priming. Mean proportions of tetramer+ cells as a percentage of CD8 cells (± SEM) for each group are shown. (B) Progression of B16-F10-gp33 tumors implanted s.c. 10 d after priming. Mean tumor sizes per group ± SEM are shown. An additional control group (n = 5) that did not receive DCs was included.

Mentions: We have shown that PDCs can efficiently present an endogenous antigen and prime naive CTL precursor. We extended these results by analyzing the ability of peptide-pulsed PDCs to prime antigen-specific CTLs. We pulsed PDCs and MDCs with the LCMV gp34–41 peptide (Kb restricted) and monitored ex vivo LCMV gp34-specific CTLs by tetramer staining. In accordance with what was observed previously, CpG-matured PDCs and MDCs induced similar proliferations of LCMV gp34-CTL; immature MDCs were somewhat intermediate, and no priming was induced by immature PDCs (Fig. 9 A).


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)

Priming by CpG-matured PDCs induces protective CTL responses. C57BL/6 mice (n = 5) were primed by intravenous injection of 2 × 105 immature or CpG-matured MDC or PDCs pulsed with 1 μg/ml LCMV gp34–41 peptide. Control animals were injected with unpulsed CpG-DCs. (A) CTL responses were assessed in the blood by FACS® analysis using LCMV gp34–41-H-2-Kb tetramers 7 d after priming. Mean proportions of tetramer+ cells as a percentage of CD8 cells (± SEM) for each group are shown. (B) Progression of B16-F10-gp33 tumors implanted s.c. 10 d after priming. Mean tumor sizes per group ± SEM are shown. An additional control group (n = 5) that did not receive DCs was included.
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Related In: Results  -  Collection

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

fig9: Priming by CpG-matured PDCs induces protective CTL responses. C57BL/6 mice (n = 5) were primed by intravenous injection of 2 × 105 immature or CpG-matured MDC or PDCs pulsed with 1 μg/ml LCMV gp34–41 peptide. Control animals were injected with unpulsed CpG-DCs. (A) CTL responses were assessed in the blood by FACS® analysis using LCMV gp34–41-H-2-Kb tetramers 7 d after priming. Mean proportions of tetramer+ cells as a percentage of CD8 cells (± SEM) for each group are shown. (B) Progression of B16-F10-gp33 tumors implanted s.c. 10 d after priming. Mean tumor sizes per group ± SEM are shown. An additional control group (n = 5) that did not receive DCs was included.
Mentions: We have shown that PDCs can efficiently present an endogenous antigen and prime naive CTL precursor. We extended these results by analyzing the ability of peptide-pulsed PDCs to prime antigen-specific CTLs. We pulsed PDCs and MDCs with the LCMV gp34–41 peptide (Kb restricted) and monitored ex vivo LCMV gp34-specific CTLs by tetramer staining. In accordance with what was observed previously, CpG-matured PDCs and MDCs induced similar proliferations of LCMV gp34-CTL; immature MDCs were somewhat intermediate, and no priming was induced by immature PDCs (Fig. 9 A).

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