Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells

Allam, Jean‐Pierre; Peng, Wenming; Appel, T.; Wenghoefer, Matthias; Niederhagen, Bernd; Bieber, Thomas; Bergé, Stefaan; Novak, Natalija

doi:10.1016/j.jaci.2007.09.045

Cited by 144 publications

(129 citation statements)

References 33 publications

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“…These cells display an immature phenotype. Upon Toll-like receptor 4 (TLR4) ligation, they up-regulate IL-10 and TGFb production, resulting in their ability to induce IL-10 and TGFb-producing T cells with regulatory characteristics (29,30). The role of dermal Langerhans cells in peptide immunotherapy has not been studied to date.…”

Section: Route Of Administration and Modulation Of Immunitymentioning

confidence: 99%

Mechanisms of Peptide Immunotherapy in Allergic Airways Disease

Larché

2014

Annals ATS

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Allergen immunotherapy with whole proteins is clinically efficacious but requires a protracted treatment period because of frequent allergic adverse events. A combination of duration of treatment and adverse events leads to poor compliance. Short synthetic peptides containing the major immunodominant T cell epitopes of allergenic proteins have been shown to reduce IgE cross-linking ability, thereby leading to fewer allergic adverse events following their administration to patients with allergies. Peptide immunotherapy has been shown to result in clinically meaningful efficacy in several Phase II, randomized, double-blind, placebo-controlled clinical trials. Exactly how peptide immunotherapy achieves its efficacy remains incompletely understood, but the mechanisms are thought to include immune deviation and induction of regulatory T cells capable of suppressing allergen-specific immune responses. Limited data are available on the effects of peptide therapy on humoral immune responses. Induction of allergen-specific IgG has been observed after peptide therapy, but the levels of antibody induced were much lower than generally seen with the utilization of whole allergen approaches. Thus, the immunological mechanisms of peptide immunotherapy appear to overlap, although not completely, with those seen in whole allergen therapy. Further studies are required to fully elucidate mechanisms of action.

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Section: Route Of Administration and Modulation Of Immunitymentioning

confidence: 99%

Mechanisms of Peptide Immunotherapy in Allergic Airways Disease

Larché

2014

Annals ATS

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“…A recent study has shown that B7-1 and B7-2 have significant implications for the manipulation of immune responses and tolerance related with regulatory T cells (35). In addition, TLR4 ligation enhances the expression of B7-1 and decreases B7-2 on human oral mucosal Langerhans cells with tolerogenic properties, and contributes to the tolerogenic state (36). These reports suggest that bovine WC1 ϩ ␥␦ T cells of PBMC may have some tolerogenic functions.…”

Section: Discussionmentioning

confidence: 98%

Anterior Pituitary Progenitor Cells Express Costimulatory Molecule 4Ig-B7-H3

Nagai

Aso

Ogasawara

et al. 2008

The Journal of Immunology

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Stem/Progenitor cells in the postnatal pituitary gland are embedded in a marginal cell layer around Rathke’s pouch. However, the nature and behavior of anterior pituitary progenitor cells remain unclear. We established bovine anterior pituitary progenitor cell line (BAPC)-1 from the anterior pituitary gland, which expressed stem/progenitor cell-related genes and several inflammatory cytokines. To characterize and localize these pituitary progenitor cells, we produced a mAb (12B mAb) against BAPC-1. The 12B mAb recognized the 4Ig-B7-H3 molecule, which is a costimulatory molecule and negative regulator in T cell activation. WC1+ γδ T cells in young bovine PBMC express the 4Ig-B7-H3 molecule, but few or no 4Ig-B7-H3-immunoreactive cells are expressed in PBMC in adult cattle. The 12B-immunoreactive cells in the bovine anterior pituitary gland were localized around Rathke’s pouch and expressed IL-18 and MHC class II. However, the number of 12B-immunoreactive cells was lower in adult than in young cattle. BAPC-1 expressed IL-18 and MHC class II, and demonstrated phagocytotic activity. BAPC-1 also had the ability to promote CD25 expression in PBMC after 5 days of coculture, and blocking 4Ig-B7-H3 × 12B mAb enhanced their expression of CD25. In addition, the 12B-immunoreactive cells were observed around the pars tuberalis closely bordering the median eminence and in the blood vessels of the primary portal plexus in the anterior pituitary gland. These results suggest that an established BAPC-1 may originate from these progenitor cells, and that the progenitor cells with 4Ig-B7-H3 may play a critical role in the immunoendocrine network.

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“…The immunologic mechanisms of SLIT are similar to SCIT. They involve increased blocking IgG4, IgA antibodies, activation of Treg cells, increased IL-10 production and increased numbers of sublingual FOXP3-expressing T cells [56][57][58]. However, the magnitude of the changes, especially increase in specific IgG4 response, is rather modest.…”

Section: Routes Of Vaccine Administrationmentioning

confidence: 99%

Novel immunotherapy vaccine development

Jutel

Akdiş

2014

Current Opinion in Allergy &Amp; Clinical Immunology

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PURPOSE OF REVIEW: Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept -as well as large, multicenter clinical studies. RECENT FINDINGS: The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. SUMMARY: The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients. Purpose of reviewAllergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-ofconcept -as well as large, multicenter clinical studies. Recent findingsThe most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. SummaryThe cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.

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Toll-like receptor 4 ligation enforces tolerogenic properties of oral mucosal Langerhans cells

Cited by 144 publications

References 33 publications

Mechanisms of Peptide Immunotherapy in Allergic Airways Disease

Mechanisms of Peptide Immunotherapy in Allergic Airways Disease

Anterior Pituitary Progenitor Cells Express Costimulatory Molecule 4Ig-B7-H3

Novel immunotherapy vaccine development

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