The Dendritic Cell Populations of Mouse Lymph Nodes

Henri, Sandrine; Vremec, David; Kamath, Arun T.; Waithman, Jason; Williams, S E; Benoist, Christophe; Burnham, Kim; Saeland, Sem; Handman, Emanuela; Shortman, Ken

doi:10.4049/jimmunol.167.2.741

Cited by 398 publications

(401 citation statements)

References 36 publications

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“…Murine LCs and other dendritic cells migrating from skin have been shown to express both CD11c and CD11b surface molecules. 55,56 As illustrated in Figure 3b-c, protein transport to the lymph nodes was detected following treatment with a (Poly-1/ova) 50 LbL patch, when examining both the total lymph node cell population as well as individual cell subsets. Though CD11c + CD11b + dendritic cells make up only a few percent of the total lymph node cells (e.g., as shown in the CD11c vs. CD11b flow cytometry plot for ova − cells), these cells were greatly preferentially enriched in the ova + cell population, with ~64% of ova + cells being of the CD11c + CD11b + subset ( Figure 3b).…”

Section: Resultsmentioning

confidence: 98%

Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery

Su¹,

Kim²,

Kim³

et al. 2009

ACS Nano

155

120

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We describe protein-and oligonucleotide-loaded layer-by-layer (LbL)-assembled multiplayer films incorporating a hydrolytically degradable polymer for transcutaneous drug or vaccine delivery. Films were constructed based on electrostatic interactions between a cationic poly(β-amino ester) (denoted Poly-1) with a model protein antigen, ovalbumin (ova), and/or immunostimulatory CpG (Cytosine-phosphate diester-Guanine rich) DNA oligonucleotide adjuvant molecules. Linear growth of nanoscale Poly-1/ova bilayers was observed. Dried ova protein-loaded films rapidly deconstructed when rehydrated in saline solutions, releasing ova as non-aggregated/non-degraded protein, suggesting that the structure of biomolecules integrated into these multilayer films are preserved during release. Using confocal fluorescence microscopy and an in vivo murine ear skin model, we demonstrated delivery of ova from LbL films into barrierdisrupted skin, uptake of the protein by skin-resident antigen-presenting cells (Langerhans cells), and transport of the antigen to the skin-draining lymph nodes. Dual incorporation of ova and CpG oligonucleotides into the nanolayers of LbL films enabled dual release of the antigen and adjuvant with distinct kinetics for each component; ova was rapidly released while CpG was released in a relatively sustained manner. Applied as skin patches, these films delivered ova and CpG to Langerhans Cells in the skin. To our knowledge, this is the first demonstration of LbL films applied for the delivery of biomolecules into skin. This approach provides a new route for storage of vaccines and other immunotherapeutics in a solid-state thin film for subsequent delivery into the immunologically-rich milieu of the skin.

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Section: Resultsmentioning

confidence: 98%

Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery

Su¹,

Kim²,

Kim³

et al. 2009

ACS Nano

155

120

View full text Add to dashboard Cite

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“…Both antigen and adjuvant were essentially (>90%) associated with CD205 + CD8 -CD11b + MHC class II hi CD11c + LN DC, indicating their peripheral origin [17]. These DC are likely to result from the maturation and migration of peripheral DC following interaction with IC31.…”

Section: Discussionmentioning

confidence: 96%

“…Five DC subpopulations have been identified in LN [17], which can be simply delineated in three populations according to CD8 and CD205 expression: two residential populations, CD205 -CD8 -CD11b + (including CD4 -and minor CD4 + populations) and the cross-priming CD205 + CD8 + CD11b -DC, as well as peripheral tissue-derived CD205 + CD8 -CD11b + DC (including Langerhans' cells and dermal DC, Fig. 4A).…”

Section: Phenotype Of Ag85b-esat-6 and Ic31-associated DC Following Imentioning

confidence: 99%

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

et al. 2008

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Vaccine efficacy largely depends upon DC targeting and activation. The most potent TLR soluble ligands induce diffuse DC activation, which may be associated with marked pro‐inflammatory responses and possibly adverse effects. This raises the concern that effective vaccine adjuvants may similarly rely on widespread DC activation. Using a promising candidate vaccine against tuberculosis (fusion protein of Ag85B and 6‐kDa early secretory antigenic target (ESAT‐6)) formulated in the potent IC31® adjuvant, DC targeting and activation was studied in vivo, following the fate of antigen and adjuvant in the draining lymph nodes, to define the magnitude of DC targeting/activation required in vivo to induce protective vaccine responses. Unexpectedly, protective IFN‐γ‐mediated Ag85B‐ESAT‐6/IC31® responses were associated to the activation of a minute population (less than 0.3%) of CD11c+ lymph node DC, without detectable systemic pro‐inflammatory responses. This activated peripheral tissue‐derived DC population, characterized by enhanced CD80, CD86, CD40 and IL‐12p40 expression, was only identified when focusing on adjuvant‐ or antigen‐labeled CD11c+ DC, which were found to support T cell proliferation. Immunization with aluminum hydroxide adjuvant (Alum) resulted in a similar proportion of antigen‐associated DC but without detectable enhancement of CD80, CD86, CD40 or IL‐12p40 expression. Thus, potent protective IFN‐γ‐producing responses may be elicited by the exquisite activation of a minute number of in vivo targeted DC.

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“…This makes it difficult to identify and characterize those DC that have responded to an added peripheral stimulus. Therefore, in many instances DC thought to have arrived via lymph to LN in mice have been described as a homogeneous population of interstitial DC [7,8].…”

Section: Introductionmentioning

confidence: 99%

A distinct subset of intestinal dendritic cells responds selectively to oral TLR7/8 stimulation

Yrlid¹,

Cerovic

Milling³

et al. 2006

Eur J Immunol

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The intestinal innate immune system continually interacts with commensal bacteria, thus oral vaccines should induce extra/alternative activation of DC, potentially through TLR. To examine this we collected intestinal lymph DC (iL-DC) under steady-state conditions and after feeding resiquimod (R-848), a synthetic TLR7/8 ligand, which we showed induces complete emptying of gut DC into lymph. iL-DC are heterogeneous with subset-specific functions. In this study we determined the kinetics of iL-DC subset release, activation and cytokine secretion induced by R-848. We show that L-DC comprise three distinct subsets (CD172a high , CD172a int and CD172a low ) present with similar frequencies in intestinal but not hepatic lymph. No iL-DC express TLR7 mRNA, and only CD172a + iL-DC express TLR8. However, after oral R-848 administration, output of all three subsets increases dramatically. CD172a high DC release precedes that of CD172a low DC, and the increased frequency of CD25 high iL-DC is restricted to the two CD172a + subsets. After feeding R-848 only CD172a high iL-DC secrete IL-6 and IL-12p40. However, CD172a int and CD172a high DC secrete similar but markedly lower amounts when stimulated in vitro. These results highlight the importance of in vivo approaches to assess adjuvant effects on DC and give novel insights into the subset-specific effects of an oral TLR ligand on intestinal DC.

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The Dendritic Cell Populations of Mouse Lymph Nodes

Cited by 398 publications

References 36 publications

Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery

Layer-by-Layer-Assembled Multilayer Films for Transcutaneous Drug and Vaccine Delivery

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

A distinct subset of intestinal dendritic cells responds selectively to oral TLR7/8 stimulation

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