Limits...
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.

Show MeSH

Related in: MedlinePlus

Lack of presentation of soluble ovalbumin by bone marrow–derived PDCs. BM cultures were pulsed on day 10 with 500 μg /ml of soluble ovalbumin in the presence or absence of CpG. MDC and PDCs were sorted on day 11. C57BL/6 mice (n = 3) were primed by intravenous injection of 105 cells and boosted after 10 d with vaccinia virus encoding full-length ovalbumin. (A) CTL responses were assessed in the blood by FACS® analysis using SIINFEKL-H-2-Kb tetramers 7 d after boosting. Mean proportions of tetramer+ cells as a percentage of CD8 cells (± SEM) for each group are shown. (B) IFN-γ ELISPOT was performed on splenocytes to assess responsiveness to ovalbumin MHC class I (SIINFEKL) and class II–restricted peptides (each at 10 μg/ml) 10 d after boosting. All animals showed comparable responses to PHA stimulation (not depicted).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2211835&req=5

fig10: Lack of presentation of soluble ovalbumin by bone marrow–derived PDCs. BM cultures were pulsed on day 10 with 500 μg /ml of soluble ovalbumin in the presence or absence of CpG. MDC and PDCs were sorted on day 11. C57BL/6 mice (n = 3) were primed by intravenous injection of 105 cells and boosted after 10 d with vaccinia virus encoding full-length ovalbumin. (A) CTL responses were assessed in the blood by FACS® analysis using SIINFEKL-H-2-Kb tetramers 7 d after boosting. Mean proportions of tetramer+ cells as a percentage of CD8 cells (± SEM) for each group are shown. (B) IFN-γ ELISPOT was performed on splenocytes to assess responsiveness to ovalbumin MHC class I (SIINFEKL) and class II–restricted peptides (each at 10 μg/ml) 10 d after boosting. All animals showed comparable responses to PHA stimulation (not depicted).

Mentions: Fig. S1 shows the phenotype of immature and CpG-matured PDCs and MDCs isolated from FLT3-L–supplemented bone marrow cultures. Fig. S2 supplements Fig. 1 and shows priming of SMCY738–746-specific CTLs by CpG-matured PDCs. Fig. S3 shows the phenotype of immature and CpG-matured PDCs differentiated from type I IFN receptor–deficient mice (129A) and wild-type 129 S1 mice. Fig. S4 supplements Fig. 10 and shows priming of OVA257–264-specific CTLs by peptide-pulsed mature PDCs. Online supplemental material is available at http://www.jem.org/cgi/content/full/jem.20031059/DC1.


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)

Lack of presentation of soluble ovalbumin by bone marrow–derived PDCs. BM cultures were pulsed on day 10 with 500 μg /ml of soluble ovalbumin in the presence or absence of CpG. MDC and PDCs were sorted on day 11. C57BL/6 mice (n = 3) were primed by intravenous injection of 105 cells and boosted after 10 d with vaccinia virus encoding full-length ovalbumin. (A) CTL responses were assessed in the blood by FACS® analysis using SIINFEKL-H-2-Kb tetramers 7 d after boosting. Mean proportions of tetramer+ cells as a percentage of CD8 cells (± SEM) for each group are shown. (B) IFN-γ ELISPOT was performed on splenocytes to assess responsiveness to ovalbumin MHC class I (SIINFEKL) and class II–restricted peptides (each at 10 μg/ml) 10 d after boosting. 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

fig10: Lack of presentation of soluble ovalbumin by bone marrow–derived PDCs. BM cultures were pulsed on day 10 with 500 μg /ml of soluble ovalbumin in the presence or absence of CpG. MDC and PDCs were sorted on day 11. C57BL/6 mice (n = 3) were primed by intravenous injection of 105 cells and boosted after 10 d with vaccinia virus encoding full-length ovalbumin. (A) CTL responses were assessed in the blood by FACS® analysis using SIINFEKL-H-2-Kb tetramers 7 d after boosting. Mean proportions of tetramer+ cells as a percentage of CD8 cells (± SEM) for each group are shown. (B) IFN-γ ELISPOT was performed on splenocytes to assess responsiveness to ovalbumin MHC class I (SIINFEKL) and class II–restricted peptides (each at 10 μg/ml) 10 d after boosting. All animals showed comparable responses to PHA stimulation (not depicted).
Mentions: Fig. S1 shows the phenotype of immature and CpG-matured PDCs and MDCs isolated from FLT3-L–supplemented bone marrow cultures. Fig. S2 supplements Fig. 1 and shows priming of SMCY738–746-specific CTLs by CpG-matured PDCs. Fig. S3 shows the phenotype of immature and CpG-matured PDCs differentiated from type I IFN receptor–deficient mice (129A) and wild-type 129 S1 mice. Fig. S4 supplements Fig. 10 and shows priming of OVA257–264-specific CTLs by peptide-pulsed mature PDCs. Online supplemental material is available at http://www.jem.org/cgi/content/full/jem.20031059/DC1.

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