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Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein- and polysaccharide-specific immunoglobulin isotype responses in vivo through distinct mechanisms.

Colino J, Shen Y, Snapper CM - J. Exp. Med. (2002)

Bottom Line: Immature bone marrow-derived myeloid dendritic cells (BMDCs) are induced to undergo phenotypic maturation and secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-12, and IL-10 when pulsed in vitro with intact Streptococcus pneumoniae.After transfer to naive mice, pulsed BMDCs induce immunoglobulin (Ig) isotype responses specific for both protein and polysaccharide pneumococcal antigens, having in common the requirement for viable BMDCs, T cells, and B7-dependent costimulation in the recipient mice.Whereas primary Ig isotype responses to bacterial proteins uniformly require BMDC expression of major histocompatibility complex class II, CD40, and B7, and the secretion of IL-6, but not IL-12, similar requirements for antipolysaccharide Ig responses were only observed for the IgG1 isotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

ABSTRACT
Immature bone marrow-derived myeloid dendritic cells (BMDCs) are induced to undergo phenotypic maturation and secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-12, and IL-10 when pulsed in vitro with intact Streptococcus pneumoniae. After transfer to naive mice, pulsed BMDCs induce immunoglobulin (Ig) isotype responses specific for both protein and polysaccharide pneumococcal antigens, having in common the requirement for viable BMDCs, T cells, and B7-dependent costimulation in the recipient mice. Whereas primary Ig isotype responses to bacterial proteins uniformly require BMDC expression of major histocompatibility complex class II, CD40, and B7, and the secretion of IL-6, but not IL-12, similar requirements for antipolysaccharide Ig responses were only observed for the IgG1 isotype.

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Role of BMDCs derived cytokines in the induction of antiprotein and antipolysaccharide antibody responses in vivo. 106 BMDCs obtained from IL-6−/−, IL-12−/−, IL-10−/−, TNF-α−/−, or wild-type mice were pulsed with S. pneumoniae type 14 and injected intravenous into wild-type mice of the corresponding genetic background. Sera were collected 14 d later for determination of antigen-specific Ig isotype titers by ELISA. The asterisks (*) indicates statistically significant differences (P < 0.05) for a particular isotype between the antigen specific responses induced by cytokine-deficient versus wild-type BMDCs.
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fig8: Role of BMDCs derived cytokines in the induction of antiprotein and antipolysaccharide antibody responses in vivo. 106 BMDCs obtained from IL-6−/−, IL-12−/−, IL-10−/−, TNF-α−/−, or wild-type mice were pulsed with S. pneumoniae type 14 and injected intravenous into wild-type mice of the corresponding genetic background. Sera were collected 14 d later for determination of antigen-specific Ig isotype titers by ELISA. The asterisks (*) indicates statistically significant differences (P < 0.05) for a particular isotype between the antigen specific responses induced by cytokine-deficient versus wild-type BMDCs.

Mentions: Finally, to determine whether BMDC-derived cytokines play a role in Ig responses to S. pneumoniae, we used BMDCs obtained from mice genetically deficient in TNF-α, IL-6, IL-12, and IL-10. IL-6−/− BMDCs showed a striking defect in the induction of IgG anti-PspA of all isotypes, and IgG1 and IgG2b anti-Cps14, with a more modest reduction in IgG1 anti-PC (Fig. 8) . BMDCs lacking in IL-10 or TNF-α demonstrated much more limited defects; IL-10−/− BMDCs elicited a diminished IgG1 anti-PspA response relative to wild-type BMDCs whereas TNF-α−/− BMDCs elicited reduced IgG2b anti-Cps14. A lack of IL-12 expression by BMDCs had no significant effects on either the anti-PspA or antipolysaccharide responses. BMDCs obtained from TNF-α−/−, IL-6−/−, or IL-12−/− mice did not differ significantly from wild-type BMDCs in their in vitro phagocytic capacity, secretion of cytokines, and cell surface phenotype before or after exposure to S. pneumoniae (data not shown). However, whereas IL-10−/− and wild-type BMDCs showed a similar cell surface phenotype before pulsing with S. pneumoniae, exposure to bacteria resulted in a significantly greater upregulation of MHC class II and CD86 in IL-10−/− BMDCs relative to wild-type BMDCs (2–3-fold increase in MFI). Enhanced expression of MHC class II and CD86 was also observed in cultures of wild-type, pulsed BMDCs treated with a neutralizing anti–IL-10 mAb. Finally, addition of IL-10 to IL-10−/− pulsed BMDC cultures reversed the increased enhancement of MHC class II and CD86 relative to wild-type BMDCs (data not shown). These data indicated that IL-10 downregulates BMDC maturation in an autocrine manner.


Dendritic cells pulsed with intact Streptococcus pneumoniae elicit both protein- and polysaccharide-specific immunoglobulin isotype responses in vivo through distinct mechanisms.

Colino J, Shen Y, Snapper CM - J. Exp. Med. (2002)

Role of BMDCs derived cytokines in the induction of antiprotein and antipolysaccharide antibody responses in vivo. 106 BMDCs obtained from IL-6−/−, IL-12−/−, IL-10−/−, TNF-α−/−, or wild-type mice were pulsed with S. pneumoniae type 14 and injected intravenous into wild-type mice of the corresponding genetic background. Sera were collected 14 d later for determination of antigen-specific Ig isotype titers by ELISA. The asterisks (*) indicates statistically significant differences (P < 0.05) for a particular isotype between the antigen specific responses induced by cytokine-deficient versus wild-type BMDCs.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2196017&req=5

fig8: Role of BMDCs derived cytokines in the induction of antiprotein and antipolysaccharide antibody responses in vivo. 106 BMDCs obtained from IL-6−/−, IL-12−/−, IL-10−/−, TNF-α−/−, or wild-type mice were pulsed with S. pneumoniae type 14 and injected intravenous into wild-type mice of the corresponding genetic background. Sera were collected 14 d later for determination of antigen-specific Ig isotype titers by ELISA. The asterisks (*) indicates statistically significant differences (P < 0.05) for a particular isotype between the antigen specific responses induced by cytokine-deficient versus wild-type BMDCs.
Mentions: Finally, to determine whether BMDC-derived cytokines play a role in Ig responses to S. pneumoniae, we used BMDCs obtained from mice genetically deficient in TNF-α, IL-6, IL-12, and IL-10. IL-6−/− BMDCs showed a striking defect in the induction of IgG anti-PspA of all isotypes, and IgG1 and IgG2b anti-Cps14, with a more modest reduction in IgG1 anti-PC (Fig. 8) . BMDCs lacking in IL-10 or TNF-α demonstrated much more limited defects; IL-10−/− BMDCs elicited a diminished IgG1 anti-PspA response relative to wild-type BMDCs whereas TNF-α−/− BMDCs elicited reduced IgG2b anti-Cps14. A lack of IL-12 expression by BMDCs had no significant effects on either the anti-PspA or antipolysaccharide responses. BMDCs obtained from TNF-α−/−, IL-6−/−, or IL-12−/− mice did not differ significantly from wild-type BMDCs in their in vitro phagocytic capacity, secretion of cytokines, and cell surface phenotype before or after exposure to S. pneumoniae (data not shown). However, whereas IL-10−/− and wild-type BMDCs showed a similar cell surface phenotype before pulsing with S. pneumoniae, exposure to bacteria resulted in a significantly greater upregulation of MHC class II and CD86 in IL-10−/− BMDCs relative to wild-type BMDCs (2–3-fold increase in MFI). Enhanced expression of MHC class II and CD86 was also observed in cultures of wild-type, pulsed BMDCs treated with a neutralizing anti–IL-10 mAb. Finally, addition of IL-10 to IL-10−/− pulsed BMDC cultures reversed the increased enhancement of MHC class II and CD86 relative to wild-type BMDCs (data not shown). These data indicated that IL-10 downregulates BMDC maturation in an autocrine manner.

Bottom Line: Immature bone marrow-derived myeloid dendritic cells (BMDCs) are induced to undergo phenotypic maturation and secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-12, and IL-10 when pulsed in vitro with intact Streptococcus pneumoniae.After transfer to naive mice, pulsed BMDCs induce immunoglobulin (Ig) isotype responses specific for both protein and polysaccharide pneumococcal antigens, having in common the requirement for viable BMDCs, T cells, and B7-dependent costimulation in the recipient mice.Whereas primary Ig isotype responses to bacterial proteins uniformly require BMDC expression of major histocompatibility complex class II, CD40, and B7, and the secretion of IL-6, but not IL-12, similar requirements for antipolysaccharide Ig responses were only observed for the IgG1 isotype.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

ABSTRACT
Immature bone marrow-derived myeloid dendritic cells (BMDCs) are induced to undergo phenotypic maturation and secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-12, and IL-10 when pulsed in vitro with intact Streptococcus pneumoniae. After transfer to naive mice, pulsed BMDCs induce immunoglobulin (Ig) isotype responses specific for both protein and polysaccharide pneumococcal antigens, having in common the requirement for viable BMDCs, T cells, and B7-dependent costimulation in the recipient mice. Whereas primary Ig isotype responses to bacterial proteins uniformly require BMDC expression of major histocompatibility complex class II, CD40, and B7, and the secretion of IL-6, but not IL-12, similar requirements for antipolysaccharide Ig responses were only observed for the IgG1 isotype.

Show MeSH
Related in: MedlinePlus