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Cross-linking the B7 family molecule B7-DC directly activates immune functions of dendritic cells.

Nguyen LT, Radhakrishnan S, Ciric B, Tamada K, Shin T, Pardoll DM, Chen L, Rodriguez M, Pease LR - J. Exp. Med. (2002)

Bottom Line: Systemic administration of the antibody has an equivalent effect on DCs transferred at a distant site.These findings implicate B7-DC expressed on DCs in bidirectional communication.In addition to the established costimulatory and inhibitory functions associated with B7-DC, this molecule can also function as a conduit for extracellular signals to DCs modifying DC functions.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, MN 55905, USA.

ABSTRACT
B7-DC molecules are known to function as ligands on antigen-presenting cells (APCs), enhancing T cell activation. In this study, cross-linking B7-DC with the monoclonal antibody sHIgM12 directly potentiates dendritic cell (DC) function by enhancing DC presentation of major histocompatibility complex-peptide complexes, promoting DC survival; and increasing secretion of interleukin (IL)-12p70, a key T helper cell type 1 promoting cytokine. Furthermore, ex vivo treatment of DCs or systemic treatment of mice with sHIgM12 increases the number of transplanted DCs that reach draining lymph nodes and increases the ability of lymph node APCs to activate naive T cells. Systemic administration of the antibody has an equivalent effect on DCs transferred at a distant site. These findings implicate B7-DC expressed on DCs in bidirectional communication. In addition to the established costimulatory and inhibitory functions associated with B7-DC, this molecule can also function as a conduit for extracellular signals to DCs modifying DC functions.

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Systemic sHIgM12 treatment increases the number of adoptively transferred DCs recovered from the draining lymph node. Untreated GFP+ DCs were injected (day 0) into the footpad of mice that had received intravenous injections of sHIgM12 or pHIgM on days –1, 0, +1. Ipsilateral and contralateral draining lymph nodes were recovered 48 h later. Staining and flow cytometric analysis was performed as described in Materials and Methods.
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fig4: Systemic sHIgM12 treatment increases the number of adoptively transferred DCs recovered from the draining lymph node. Untreated GFP+ DCs were injected (day 0) into the footpad of mice that had received intravenous injections of sHIgM12 or pHIgM on days –1, 0, +1. Ipsilateral and contralateral draining lymph nodes were recovered 48 h later. Staining and flow cytometric analysis was performed as described in Materials and Methods.

Mentions: While the finding that of ex vivo antibody treatment influences the ability of adoptively transferred DCs to reach the draining lymph nodes has important therapeutic implications, we addressed the question of whether systemic administration of the antibody could have similar affects. Untreated GFP+ DCs were adoptively transferred into the footpad of naive animals to evaluate whether systemic administration of the antibody sHIgM12 would influence the number of DCs reaching draining lymph nodes. A fivefold increase in GFP+ DCs were recovered from draining lymph nodes in comparison to nodes recovered from mice receiving systemic control IgM antibody treatment (Fig. 4) . This finding demonstrates that sIgM12 antibody administered intravenously can influence the ability of distant DCs to reach sites of T cell activation.


Cross-linking the B7 family molecule B7-DC directly activates immune functions of dendritic cells.

Nguyen LT, Radhakrishnan S, Ciric B, Tamada K, Shin T, Pardoll DM, Chen L, Rodriguez M, Pease LR - J. Exp. Med. (2002)

Systemic sHIgM12 treatment increases the number of adoptively transferred DCs recovered from the draining lymph node. Untreated GFP+ DCs were injected (day 0) into the footpad of mice that had received intravenous injections of sHIgM12 or pHIgM on days –1, 0, +1. Ipsilateral and contralateral draining lymph nodes were recovered 48 h later. Staining and flow cytometric analysis was performed as described in Materials and Methods.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2193990&req=5

fig4: Systemic sHIgM12 treatment increases the number of adoptively transferred DCs recovered from the draining lymph node. Untreated GFP+ DCs were injected (day 0) into the footpad of mice that had received intravenous injections of sHIgM12 or pHIgM on days –1, 0, +1. Ipsilateral and contralateral draining lymph nodes were recovered 48 h later. Staining and flow cytometric analysis was performed as described in Materials and Methods.
Mentions: While the finding that of ex vivo antibody treatment influences the ability of adoptively transferred DCs to reach the draining lymph nodes has important therapeutic implications, we addressed the question of whether systemic administration of the antibody could have similar affects. Untreated GFP+ DCs were adoptively transferred into the footpad of naive animals to evaluate whether systemic administration of the antibody sHIgM12 would influence the number of DCs reaching draining lymph nodes. A fivefold increase in GFP+ DCs were recovered from draining lymph nodes in comparison to nodes recovered from mice receiving systemic control IgM antibody treatment (Fig. 4) . This finding demonstrates that sIgM12 antibody administered intravenously can influence the ability of distant DCs to reach sites of T cell activation.

Bottom Line: Systemic administration of the antibody has an equivalent effect on DCs transferred at a distant site.These findings implicate B7-DC expressed on DCs in bidirectional communication.In addition to the established costimulatory and inhibitory functions associated with B7-DC, this molecule can also function as a conduit for extracellular signals to DCs modifying DC functions.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, MN 55905, USA.

ABSTRACT
B7-DC molecules are known to function as ligands on antigen-presenting cells (APCs), enhancing T cell activation. In this study, cross-linking B7-DC with the monoclonal antibody sHIgM12 directly potentiates dendritic cell (DC) function by enhancing DC presentation of major histocompatibility complex-peptide complexes, promoting DC survival; and increasing secretion of interleukin (IL)-12p70, a key T helper cell type 1 promoting cytokine. Furthermore, ex vivo treatment of DCs or systemic treatment of mice with sHIgM12 increases the number of transplanted DCs that reach draining lymph nodes and increases the ability of lymph node APCs to activate naive T cells. Systemic administration of the antibody has an equivalent effect on DCs transferred at a distant site. These findings implicate B7-DC expressed on DCs in bidirectional communication. In addition to the established costimulatory and inhibitory functions associated with B7-DC, this molecule can also function as a conduit for extracellular signals to DCs modifying DC functions.

Show MeSH
Related in: MedlinePlus