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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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Requirements for BMDC expression of MHC class II molecules for induction of antigen-specific Ig isotype responses. Groups (n = 5) C57BL/6 mice were injected intravenous with 106 BMDCs obtained from MHC class II−/− mice or 106 BMDCs obtained from the corresponding background C57BL/6 strain, both pulsed for 5 h with S. pneumoniae type 14. 14 d later, serum Ig isotype titers specific for PC, Cps14, and PspA were determined by ELISA. Statistical significance (P < 0.05) is indicated by asterisks (*).
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fig6: Requirements for BMDC expression of MHC class II molecules for induction of antigen-specific Ig isotype responses. Groups (n = 5) C57BL/6 mice were injected intravenous with 106 BMDCs obtained from MHC class II−/− mice or 106 BMDCs obtained from the corresponding background C57BL/6 strain, both pulsed for 5 h with S. pneumoniae type 14. 14 d later, serum Ig isotype titers specific for PC, Cps14, and PspA were determined by ELISA. Statistical significance (P < 0.05) is indicated by asterisks (*).

Mentions: To further understand the mechanism(s) underlying the T cell–mediated induction of antiprotein and antipolysaccharide responses to pulsed BMDCs we used BMDCs obtained from mice genetically deficient in expression of MHC class II molecules. As shown in Fig. 6 , MHC class II−/− BMDCs pulsed with S. pneumoniae failed to induce anti-PspA responses of any isotype upon transfer to naive mice. In contrast, with the exception of IgG1, both anti-PC and anti-Cps14 Ig responses to MHC class II−/− and wild-type pulsed BMDCs were similar (Fig. 6). The impairment of the IgG1 response using MHC class II−/− BMDCs was more marked for the Cps14-specific relative to the PC-specific response. Flow cytometric analysis using three anti-PC mAbs and one polyclonal anti-Cps14 mAb, in BMDCs pulsed for 24 h with S. pneumoniae, failed to detect either PC or Cps14 on the cell surface of pulsed BMDCs, but did easily detect the presence of intracellular PC (data not shown). These data argue against a direct BMDCs surface presentation of B cell epitopes for the polysaccharides studied.


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)

Requirements for BMDC expression of MHC class II molecules for induction of antigen-specific Ig isotype responses. Groups (n = 5) C57BL/6 mice were injected intravenous with 106 BMDCs obtained from MHC class II−/− mice or 106 BMDCs obtained from the corresponding background C57BL/6 strain, both pulsed for 5 h with S. pneumoniae type 14. 14 d later, serum Ig isotype titers specific for PC, Cps14, and PspA were determined by ELISA. Statistical significance (P < 0.05) is indicated by asterisks (*).
© Copyright Policy
Related In: Results  -  Collection

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

fig6: Requirements for BMDC expression of MHC class II molecules for induction of antigen-specific Ig isotype responses. Groups (n = 5) C57BL/6 mice were injected intravenous with 106 BMDCs obtained from MHC class II−/− mice or 106 BMDCs obtained from the corresponding background C57BL/6 strain, both pulsed for 5 h with S. pneumoniae type 14. 14 d later, serum Ig isotype titers specific for PC, Cps14, and PspA were determined by ELISA. Statistical significance (P < 0.05) is indicated by asterisks (*).
Mentions: To further understand the mechanism(s) underlying the T cell–mediated induction of antiprotein and antipolysaccharide responses to pulsed BMDCs we used BMDCs obtained from mice genetically deficient in expression of MHC class II molecules. As shown in Fig. 6 , MHC class II−/− BMDCs pulsed with S. pneumoniae failed to induce anti-PspA responses of any isotype upon transfer to naive mice. In contrast, with the exception of IgG1, both anti-PC and anti-Cps14 Ig responses to MHC class II−/− and wild-type pulsed BMDCs were similar (Fig. 6). The impairment of the IgG1 response using MHC class II−/− BMDCs was more marked for the Cps14-specific relative to the PC-specific response. Flow cytometric analysis using three anti-PC mAbs and one polyclonal anti-Cps14 mAb, in BMDCs pulsed for 24 h with S. pneumoniae, failed to detect either PC or Cps14 on the cell surface of pulsed BMDCs, but did easily detect the presence of intracellular PC (data not shown). These data argue against a direct BMDCs surface presentation of B cell epitopes for the polysaccharides studied.

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