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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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Requirement for recipient T cells and B7–dependent costimulation for pulsed BMDC induction of antigen-specific Ig isotypes. Groups of seven C57BL/6 mice acutely depleted of T cells by treatment with anti-CD4 and anti-CD8 mAbs (left), or blocked in their B7-dependent interactions by treatment with CTLA4Ig (right) received an intravenous injection of 106 BMDCs pulsed with S. pneumoniae type 14. The titers of antigen specific antibodies in the sera collected 14 d later were compared with their respective controls, which were treated with an irrelevant IgG2b mAb, or a control fusion protein, respectively before intravenous injection with pulsed BMDCs. Statistically significant differences (P < 0.05) between black and hatched bars are indicated by asterisks (*). Statistically significant differences (P < 0.05), between hatched and white bars by dots (M).
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fig5: Requirement for recipient T cells and B7–dependent costimulation for pulsed BMDC induction of antigen-specific Ig isotypes. Groups of seven C57BL/6 mice acutely depleted of T cells by treatment with anti-CD4 and anti-CD8 mAbs (left), or blocked in their B7-dependent interactions by treatment with CTLA4Ig (right) received an intravenous injection of 106 BMDCs pulsed with S. pneumoniae type 14. The titers of antigen specific antibodies in the sera collected 14 d later were compared with their respective controls, which were treated with an irrelevant IgG2b mAb, or a control fusion protein, respectively before intravenous injection with pulsed BMDCs. Statistically significant differences (P < 0.05) between black and hatched bars are indicated by asterisks (*). Statistically significant differences (P < 0.05), between hatched and white bars by dots (M).

Mentions: To determine the requirement for T cells in mediating Ig responses to pulsed-BMDCs we acutely depleted T cells in the recipient mice with anti-CD4 and anti-CD8 mAbs before injecting pulsed BMDCs. As shown in Fig. 5 , endogenous T cells were critical for development of IgG specific for both anti-PspA and polysaccharide antigens, whereas IgM antipolysaccharide responses showed only a partial dependence on T cells. We further wished to determine whether B7-dependent costimulation was required for these T cell–dependent effects. Mice were therefore injected with CTLA4Ig before transfer of S. pneumoniae-pulsed BMDCs. As shown in Fig. 5, functional interaction of T cells with B7 expressed on either recipient cells and/or on the injected BMDCs pulsed with S. pneumoniae, were critical for both the IgG anti-PspA and IgG anti-Cps14 responses. Significant suppression of the IgG anti-PC response was also observed after CTLA4Ig treatment, but this suppression was not absolute. These data extend our previous observations in mice immunized with free S. pneumoniae alone (6, 22).


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)

Requirement for recipient T cells and B7–dependent costimulation for pulsed BMDC induction of antigen-specific Ig isotypes. Groups of seven C57BL/6 mice acutely depleted of T cells by treatment with anti-CD4 and anti-CD8 mAbs (left), or blocked in their B7-dependent interactions by treatment with CTLA4Ig (right) received an intravenous injection of 106 BMDCs pulsed with S. pneumoniae type 14. The titers of antigen specific antibodies in the sera collected 14 d later were compared with their respective controls, which were treated with an irrelevant IgG2b mAb, or a control fusion protein, respectively before intravenous injection with pulsed BMDCs. Statistically significant differences (P < 0.05) between black and hatched bars are indicated by asterisks (*). Statistically significant differences (P < 0.05), between hatched and white bars by dots (M).
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Related In: Results  -  Collection

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fig5: Requirement for recipient T cells and B7–dependent costimulation for pulsed BMDC induction of antigen-specific Ig isotypes. Groups of seven C57BL/6 mice acutely depleted of T cells by treatment with anti-CD4 and anti-CD8 mAbs (left), or blocked in their B7-dependent interactions by treatment with CTLA4Ig (right) received an intravenous injection of 106 BMDCs pulsed with S. pneumoniae type 14. The titers of antigen specific antibodies in the sera collected 14 d later were compared with their respective controls, which were treated with an irrelevant IgG2b mAb, or a control fusion protein, respectively before intravenous injection with pulsed BMDCs. Statistically significant differences (P < 0.05) between black and hatched bars are indicated by asterisks (*). Statistically significant differences (P < 0.05), between hatched and white bars by dots (M).
Mentions: To determine the requirement for T cells in mediating Ig responses to pulsed-BMDCs we acutely depleted T cells in the recipient mice with anti-CD4 and anti-CD8 mAbs before injecting pulsed BMDCs. As shown in Fig. 5 , endogenous T cells were critical for development of IgG specific for both anti-PspA and polysaccharide antigens, whereas IgM antipolysaccharide responses showed only a partial dependence on T cells. We further wished to determine whether B7-dependent costimulation was required for these T cell–dependent effects. Mice were therefore injected with CTLA4Ig before transfer of S. pneumoniae-pulsed BMDCs. As shown in Fig. 5, functional interaction of T cells with B7 expressed on either recipient cells and/or on the injected BMDCs pulsed with S. pneumoniae, were critical for both the IgG anti-PspA and IgG anti-Cps14 responses. Significant suppression of the IgG anti-PC response was also observed after CTLA4Ig treatment, but this suppression was not absolute. These data extend our previous observations in mice immunized with free S. pneumoniae alone (6, 22).

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