In Vivo Antigen Presentation Capacity of Dendritic Cells from Oral Mucosa and Skin Draining Lymph Nodes

Wilsem, Erna van; Hoogstraten, Ingrid van; Brevé, John; Zaman, Yaved; Kraal, Georg

doi:10.1007/978-1-4615-2492-2_11

Cited by 6 publications

(3 citation statements)

References 8 publications

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“…These responses, however, can be explained by either the lower dose of antigen concentrations used or the lower number of LCs present at the mucosal site. These responses do not appear to be a result of the different antigen‐presenting capacities of DCs 17,18 . In addition, these studies did not discriminate between the functions of submucosal DCs and LCs 17,19,20 .…”

Section: Introductionmentioning

confidence: 75%

Identification of three distinct subsets of migrating dendritic cells from oral mucosa within the regional lymph nodes

Chalermsarp

Azuma

2009

Immunology

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Summary To investigate the phenotypic and migrational properties of oral mucosal dendritic cells (OMDCs), fluorescein isothiocyanate (FITC) was painted onto mouse buccal mucosa and the expression patterns of functional molecules in FITC‐bearing migrating DCs within the regional lymph nodes (RLNs) were analysed. We found three distinct subpopulations of migrating OMDCs within the RLNs: CD11chi CD207− (F1), CD11cint/lo CD207− (F2) and CD11cint/lo CD207+ (F3). The F1 DCs reached the RLNs earlier (after 24 hr) but diminished immediately. Additionally, F1 DCs expressed high levels of CD11b. The F2 DCs migrated continuously to the RLNs and maintained the highest ratio of all three fractions. The F3 DCs migrated slowly to the RLNs and demonstrated a late peak at 96 hr. In addition, F3 DCs showed the highest CD205 expression levels of all three subsets. All fractions of migrating OMDCs expressed CD80, CD86 and major histocompatibility complex class II at high levels, suggesting that all OMDCs are in a mature stage and have the potential for antigen presentation. All migrating OMDCs lacked CD8α expression. Taken together, our results indicate that the lack of CD207 is one factor that identifies submucosal DCs. Both F1 and F2 DCs lack CD207; F1 DCs are resident and F2 DCs are newly recruited following FITC application. The F3 DCs, which express CD207, are mucosal Langerhans cells that migrate later. The identification of OMDC subsets should facilitate further studies investigating the functional roles of each fraction.

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Section: Introductionmentioning

confidence: 75%

Identification of three distinct subsets of migrating dendritic cells from oral mucosa within the regional lymph nodes

Chalermsarp

Azuma

2009

Immunology

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“…Following antigen encounter at mucosal surfaces there is local capture of antigen by Langerhans-like dendritic cells (DC) followed by maturation and migration of these DC to proximal draining lymph nodes mediated by changes in expression of surface receptors involved in adhesion and trafficking such as the chemokine receptor CCR7 [70]. Murine studies show that following sublingual allergen administration, allergen-primed DC migrate to submaxillary, internal jugular and superficial cervical lymph nodes where the microenvironments favour mucosal tolerance through the production of blocking antibodies (IgG 2b in mice) [71] and the induction of T lymphocytes with suppressive function [59,72].…”

Section: Allergen Presentation To the Immune System In Slitmentioning

confidence: 99%

Sublingual Allergen Immunotherapy: Immunological Mechanisms and Prospects for Refined Vaccine Preparations

O’Hehir

Sandrini²,

Anderson³

et al. 2007

CMC

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Allergic diseases constitute a major health issue worldwide. Mainstay treatment constitutes allergen avoidance and pharmacotherapy for symptom relief, but allergen immunotherapy offers advantages of specific treatment with long lasting efficacy, and being able to modify the course of the disease. Conventional immunotherapy involves the subcutaneous injection of gradually increasing amounts of allergen extract but the use of current whole allergen extracts is restricted by the risk of adverse IgE-mediated events especially for potent allergens such as peanut and latex and for asthmatics. This has lead to interest in alternative routes of immunotherapy. Oral tolerance is a well-documented immune process and the sublingual route of administration of allergen immunotherapy is attracting interest. Recent meta-analyses show that sublingual allergen immunotherapy for grass pollen and house dust mite allergy is clinically effective and safer than injection immunotherapy. Some studies show SLIT induces changes of T cell anergy, immune deviation, blocking antibodies, and induction of regulatory T cells, as described for injection immunotherapy pointing to the need to target allergen-specific T cells, there is emergent evidence that the oral mucosa presents distinct regulatory features. Evidence suggests that oral dendritic cells play a key role in inducing tolerance especially when allergen is taken up via Fc receptor bound IgE. This suggests that although both would target allergen-specific T cells, allergen formulations may differ with respect to IgE epitopes for optimal SLIT compared with SCIT. Identification of the molecular nature of the allergen-DC receptor interaction is required to determine whether short peptides or recombinant allergen preparations and of suitable adjuvants specifically tailored for the sublingual route will allow the development of improved allergen formulations and delivery strategies for efficacy of treatment whilst decreasing IgE-mediated adverse effects.

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“…Although Okamura et al . did not assess migration of DC to draining lymph nodes and the antigen-presenting capacity of DC, previous studies demonstrated that buccal DC are involved in hapten capture and transport to draining cervicomandibullary lymph nodes [17,18]. Moreover, contact hypersensitivity can be induced by topical application of haptens on the buccal mucosa and is mediated by hapten-specific CD8 T cells, independently of CD4 T cell help, similar to the contact hypersensitivity reaction induced by skin sensitization [19,20].…”

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confidence: 99%

Dendritic cells and the handling of antigen

Dieli

2003

Clinical and Experimental Immunology

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Keywords buccal mucosa CD8 T cells dendritic cells haptensDendritic cells (DC) are a sparsely distributed, migratory group of bone marrow-derived leucocytes that are specialized for the uptake, transport, processing and presentation of antigens to T cells [1,2]. At an immature stage of development DC are considered as the first-line sentinels in immune surveillance of peripheral tissues, including epithelia of the skin and mucosal surfaces, where they sample continuously the antigenic local microenvironment by uptake of self-and exogenous antigen via macropinocytosis/endocytosis [3,4]. The efficiency of DC to initiate an immune response against infectious disease is due to their constant trafficking between peripheral tissues and draining lymph nodes. DC residing in mucocutaneous epithelia are specialized in the uptake and processing of foreign antigen. Upon antigenic stimulation in the presence of inflammatory mediators, DC mature, process antigen and become migratory; they enter secondary lymphoid organs where they use these newly acquired capabilities to induce a T cell-dependent immune response. Following migration to draining lymph nodes, DC acquire expression of co-stimulatory molecules and become efficient at presenting antigenic peptides loaded onto MHC class I and class II molecules to naive CD8 and CD4 T cells, respectively [5].Antigen presentation can lead either to priming of effector and memory T cells or to functional inactivation and T cell tolerance. Finding the factors that regulate the balance between tolerance and response is considered of paramount importance. The current view is that the critical factors lie in the nature of the antigenpresenting cell (APC) (DC versus resting B cells and tissue cells), the number of DC that reach the lymph node, their lifespan and the nature and amount of co-stimulatory molecules and cytokines they express [6]. These factors will be determined by the context in which DC are stimulated to mature. Bacterial and viral products such as lipopolysaccharides (LPS) and double-stranded RNA recruit large numbers of DC and activate them to a high stimulatory status, whereas endogenous inflammatory cytokines are much less effective [7]. CD40L and tumour necrosis factor (TNF)-related activation-induced cytokine (TRANCE) represent additional endogenous stimuli by which T cells can enhance DC stimulatory capacity and viability [8]. Accordingly, tolerance or priming will be determined by how far pathogens and/or memory T cells raise the activation state of maturing DC, i.e. high activation state and high numbers will favour priming, whereas low activation and low numbers will induce tolerance.An important issue for the development of an effective mucosal vaccine is whether DC within mucosal epithelia are involved in priming CD4 and CD8 effector T cells or may favour the development of mucosal and systemic tolerance. Indeed, although DC are present in both Peyer's patches [9] and lamina propria of the small intestine [10], the efficiency of oral immunization with protein ant...

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In Vivo Antigen Presentation Capacity of Dendritic Cells from Oral Mucosa and Skin Draining Lymph Nodes

Cited by 6 publications

References 8 publications

Identification of three distinct subsets of migrating dendritic cells from oral mucosa within the regional lymph nodes

Identification of three distinct subsets of migrating dendritic cells from oral mucosa within the regional lymph nodes

Sublingual Allergen Immunotherapy: Immunological Mechanisms and Prospects for Refined Vaccine Preparations

Dendritic cells and the handling of antigen

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