Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes TH1 cytokine expression while downregulating TH2 cytokine expression in PBMCs from human patients with ragweed allergy

Marshall, Jason D.; Abtahi, Simin; Eiden, Joseph; Tuck, Stephen; Milley, Robert; Haycock, A. Fiona; Reid, Michael; Kagey‐Sobotka, Anne; Creticos, Peter S.; Lichtenstein, Lawrence M.; Nest, Gary Van

doi:10.1067/mai.2001.116984

Cited by 123 publications

(77 citation statements)

References 31 publications

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“…Of note, IL-12 produced by DCs in response to CpG-containing ODNs was found to be able to induce IFN-c production even by established allergen-specific Th2 effectors through the upregulation on their surface of the IL-12Rb2 chain (63). Of note, even more pronounced immune deviation from Th2 to Th1 in the allergen-specific response was observed by using allergen : CpG-ODNs conjugates (64). These findings have been confirmed by in vivo studies in animal models and more recently even in humans.…”

Section: Possible Regulation Of Th2-mediated Inflammation By Immune Dmentioning

confidence: 98%

Regulatory T cells: which role in the pathogenesis and treatment of allergic disorders?

Romagnani

2005

Allergy

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Several recent data suggest the importance of different types of cells in the regulation of T‐cell effector‐mediated immune responses. However, a unique specific marker for these cells has not yet been identified. Moreover, in addition to a dedicated functional lineage, even a ‘plastic’ phenotype of regulatory T cells seems to exist. The lack of a unique specific marker for regulatory T cells, as well as their heterogeneity, make it difficult to determine whether a defect of regulatory T cells plays a role in the pathogenesis of common allergic disorders. Novel therapeutic strategies based on the induction or potentiation of regulatory T cells able to hamper allergic inflammatory reactions are desirable, but their possible efficacy and safety are not yet known. At present, therapeutic strategies able to induce an immune deviation of allergen‐specific type 2 T‐helper responses to a less polarized phenotype rather than a general immune suppression appear more realistic.

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Section: Possible Regulation Of Th2-mediated Inflammation By Immune Dmentioning

confidence: 98%

Regulatory T cells: which role in the pathogenesis and treatment of allergic disorders?

Romagnani

2005

Allergy

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“…Conjugation of CpG-ODNs to specific allergens has been tested in human clinical trials and been shown to improve the safety of allergen immunotherapy by reducing allergenicity (60)(61)(62)(63). A proposed mechanism is the deviation of the diseasepromoting Th2 responses toward a Th1 response not associated with the allergic phenotype (60,61,64). We previously observed that drug-induced IL-10-Tregs are as effective, if not more so, in inhibiting Th1 responses than Th2 responses (21), suggesting that IL-10-Tregs might impair immune deviation.…”

Section: Figurementioning

confidence: 99%

Ligation of TLR9 induced on human IL-10–secreting Tregs by 1α,25-dihydroxyvitamin D3 abrogates regulatory function

Urry¹,

Xystrakis²,

Richards³

et al. 2009

J. Clin. Invest.

137

163

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“…The Amb a 1-ISS combination was more effective in modulating the cytokine profile than the use of ISS and Amb a 1 unlinked [44]. A subsequent in vivo study demonstrated that ragweed-induced TH2 responses were shifted toward TH1 responses, with significant increases in IFN-γ [45].…”

Section: Tlr9-based Adjuvantsmentioning

confidence: 94%

Novel Approaches of Immunotherapy

Stokes

Casale

2013

Curr Treat Options Allergy

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Opinion statementAllergic diseases affect millions of adults and children in the United States. Allergen immunotherapy has been a treatment option for diseases such as allergic rhinitis, allergic asthma, and venom allergy for the last 100 years. In the last 25 years, alternative approaches to traditional subcutaneous immunotherapy have been developed. The purpose of these new therapies is two-fold: to improve safety and to improve the efficacy of allergen immunotherapy. Aluminum hydroxide has been used as an adjuvant to standard immunotherapy, but due to concerns about side effects, its use has been decreasing. The modification of allergens into allergoids has been an effective therapy in Europe, but at this time no preparations are available for use in the United States. Toll-like receptors have demonstrated mixed results with early trials in the United States, showing promise with the use of a TLR4 agonist, while a TLR9 agonist had disappointing results. Early studies with the use of virus-like particles with and without allergens have shown additional promise, and further trials are currently underway. These novel approaches may improve the immunologic response and often the clinical outcomes for the management of allergic diseases.

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Immunostimulatory sequence DNA linked to the Amb a 1 allergen promotes TH1 cytokine expression while downregulating TH2 cytokine expression in PBMCs from human patients with ragweed allergy

Cited by 123 publications

References 31 publications

Regulatory T cells: which role in the pathogenesis and treatment of allergic disorders?

Regulatory T cells: which role in the pathogenesis and treatment of allergic disorders?

Ligation of TLR9 induced on human IL-10–secreting Tregs by 1α,25-dihydroxyvitamin D3 abrogates regulatory function

Novel Approaches of Immunotherapy

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