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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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BMDC expression of CD40 and B7 is required for an optimal antiprotein response, but only for an optimal IgG1 antipolysaccharide response. 106 BMDCs obtained from CD40−/−, B7–1−/−/B7–2−/−, or wild-type mice pulsed in vitro with S. pneumoniae type 14 were injected intravenous into separate groups of wild-type mice. Serum antigen-specific Ig isotype titers 14 d after the injection were determined by ELISA. Statistically significant differences (P < 0.05) are indicated by asterisks (*).
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fig7: BMDC expression of CD40 and B7 is required for an optimal antiprotein response, but only for an optimal IgG1 antipolysaccharide response. 106 BMDCs obtained from CD40−/−, B7–1−/−/B7–2−/−, or wild-type mice pulsed in vitro with S. pneumoniae type 14 were injected intravenous into separate groups of wild-type mice. Serum antigen-specific Ig isotype titers 14 d after the injection were determined by ELISA. Statistically significant differences (P < 0.05) are indicated by asterisks (*).

Mentions: To further determine the costimulation requirements for Ig induction in response to pulsed BMDCs, we directly evaluated the importance of BMDC expression of CD40 and B7–1/B7–2 by using BMDCs obtained from mice genetically deficient in CD40, or mice doubly deficient for B7–1 and B7–2. As shown in Fig. 7 , BMDCs lacking CD40, or B7 expression were markedly defective in inducing anti-PspA responses of all isotypes relative to wild-type BMDCs. In contrast, BMDCs lacking in these cell surface molecules were defective only in induction of polysaccharide-specific IgG1. The differences in the IgG anti-PC and anti-Cps 14 responses observed when using CTLA4Ig (Fig. 5) versus B7-deficient BMDCs (Fig. 7), may reflect either compensatory costimulatory ability of BMDCs lacking B7, or more likely B7-dependent costimulation by B cells and/or macrophages in the recipient. In this regard, BMDCs derived from CD40−/−, B7–1/B7–2−/−, and MHC class II−/− mice, did not differ significantly in vitro, in phagocytic capacity, cytokine secretion, or cell surface phenotype relative to wild-type BMDCs (data not shown).


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)

BMDC expression of CD40 and B7 is required for an optimal antiprotein response, but only for an optimal IgG1 antipolysaccharide response. 106 BMDCs obtained from CD40−/−, B7–1−/−/B7–2−/−, or wild-type mice pulsed in vitro with S. pneumoniae type 14 were injected intravenous into separate groups of wild-type mice. Serum antigen-specific Ig isotype titers 14 d after the injection were determined by ELISA. Statistically significant differences (P < 0.05) are indicated by asterisks (*).
© Copyright Policy
Related In: Results  -  Collection

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

fig7: BMDC expression of CD40 and B7 is required for an optimal antiprotein response, but only for an optimal IgG1 antipolysaccharide response. 106 BMDCs obtained from CD40−/−, B7–1−/−/B7–2−/−, or wild-type mice pulsed in vitro with S. pneumoniae type 14 were injected intravenous into separate groups of wild-type mice. Serum antigen-specific Ig isotype titers 14 d after the injection were determined by ELISA. Statistically significant differences (P < 0.05) are indicated by asterisks (*).
Mentions: To further determine the costimulation requirements for Ig induction in response to pulsed BMDCs, we directly evaluated the importance of BMDC expression of CD40 and B7–1/B7–2 by using BMDCs obtained from mice genetically deficient in CD40, or mice doubly deficient for B7–1 and B7–2. As shown in Fig. 7 , BMDCs lacking CD40, or B7 expression were markedly defective in inducing anti-PspA responses of all isotypes relative to wild-type BMDCs. In contrast, BMDCs lacking in these cell surface molecules were defective only in induction of polysaccharide-specific IgG1. The differences in the IgG anti-PC and anti-Cps 14 responses observed when using CTLA4Ig (Fig. 5) versus B7-deficient BMDCs (Fig. 7), may reflect either compensatory costimulatory ability of BMDCs lacking B7, or more likely B7-dependent costimulation by B cells and/or macrophages in the recipient. In this regard, BMDCs derived from CD40−/−, B7–1/B7–2−/−, and MHC class II−/− mice, did not differ significantly in vitro, in phagocytic capacity, cytokine secretion, or cell surface phenotype relative to wild-type BMDCs (data not shown).

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