In situ expression of the costimulatory molecules CD80 and CD86 on Langerhans cells and inflammatory dendritic epidermal cells (IDEC) in atopic dermatitis

Schuller, Erich; Teichmann, Bianca; Haberstok, Jörg; Moderer, Martina; Bieber, T.; Wollenberg, Andreas

doi:10.1007/s004030100263

Cited by 60 publications

(37 citation statements)

References 27 publications

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“…Preliminary in vitro studies confirmed that this recombinant protein could bind both monocytes in PBMC and dog IgE, and enhanced allergen-induced lymphoproliferation in experimentally sensitized dogs. Previous reports including our study in dogs described enhanced expression of CD80 and CD86 in immune cells in allergic patients [13,16,21], suggesting the potential effectiveness of CTLA4-targeted vaccines for application in immunotherapy. Further investigation of this novel strategy will hopefully provide options for the treatment of allergic diseases.…”

Section: Discussionsupporting

confidence: 60%

CTLA-4 Recombinant Protein Genetically Fused to Canine Fcε Receptor Iα Enhances Allergen Specific Lymphocyte Responses in Experimentally Sensitized Dogs

Yasunaga

Tsukui

Masuda

et al. 2004

The Journal of Veterinary Medical Science

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ABSTRACT. Vaccination with a recombinant antigen fused to a targeting molecule is a potential strategy for inducing efficient immune responses. For the therapeutic purpose of allergic diseases in dogs, a DNA construct which expresses recombinant fusion protein with two functional domains, cytotoxic T lymphocyte antigen (CTLA-4) and Fcε receptor Iα, was developed to bridge antigen-presenting cells and IgE-allergen complex. The recombinant fusion protein expressed by the DNA construct was demonstrated to retain the ability to bind monocytes in PBMC and dog IgE, respectively. Additionally, the recombinant protein induced enhancement of allergen-induced lymphoproliferation in experimentally sensitized dogs under conditions of suboptimal allergen stimulation. These results indicated that the DNA construct could enhance allergen-induced immune responses in vivo, implying its usefulness for perspective application in immunotherapy in dogs. KEY WORDS: allergic disease, canine, co-stimulatory molecule, DNA immunization, immunotherapy.J. Vet. Med. Sci. 66(6): 611-617, 2004 Allergic diseases including atopic dermatitis and allergic bronchitis are caused by type 1 and type 4 hypersensitivities, and are one of the most frequently encountered diseases in veterinary medicine. As in humans, allergic diseases in dogs are caused by various allergens, and increasing numbers of dogs are suffering from dermal or respiratory symptoms derived from the IgE-mediated pathogenesis of disease. Specific immunotherapy has been applied to treat dogs with allergic diseases similar to homologous diseases in human medicine [22].Allergen-specific immunotherapy, the administration of increasingly higher doses of allergen extract, is the only curative approach toward IgE-mediated allergies [17], and can induce the alleviation or resolution of sensitivity to an allergen. Although the complex mechanisms of immunotherapy are not well understood, proposed mechanisms include the induction of "blocking antibodies" [18], a reduction in the number of eosinophils in lesions and the release of proinflammatory mediators [5], the induction of suppressor cells [15], and the altering of the Th1-Th2 cytokine balance toward Th1 dominance [5,10]. In spite of its curative potential, however, the application of immunotherapy to clinical cases of allergy is limited because of major drawbacks with the current protocol, some of which are more problematic in dogs than humans. The long duration necessary for therapy (months to years) and uncertain efficacy, which vary among reports as well as individuals, usually lead to poor compliance by patients (or owners in veterinary cases). Anaphylactic side effects are less problematic in dogs, but were reported to be a reason for cessation of therapy in some cases. It is considered that poor immunogenicity of the allergen, insufficient for the induction of Th1 dominance [5], and allergic responses against causative or other potential allergens included in the extract used for immunotherapy [17], are responsible for these drawb...

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Section: Discussionsupporting

confidence: 60%

CTLA-4 Recombinant Protein Genetically Fused to Canine Fcε Receptor Iα Enhances Allergen Specific Lymphocyte Responses in Experimentally Sensitized Dogs

Yasunaga

Tsukui

Masuda

et al. 2004

The Journal of Veterinary Medical Science

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“…Previously, epidermal DCs in inflammatory skin lesions (atopic dermatitis and psoriasis) have been classified as Langerhans cells, inflammatory dendritic epidermal cells (IDECs), and plasmacytoid DCs, by FACS techniques (28)(29)(30). Tip-DCs might contain the IDEC population because both express the integrin CD11c (unlike Langerhans cells).…”

Section: Discussionmentioning

confidence: 99%

Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)

Lowes

Chamian

Abello

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

432

379

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We find that CD11c ؉ cells with many markers of dendritic cells (DCs) are a major cell type in the skin lesions of psoriasis. These CD11c ؉ cells, which are evident in both epidermis and dermis, are the sites for the expression of two mediators of inflammation, inducible nitric oxide synthase (iNOS) and TNF-␣ in diseased skin. These cells express HLA-DR, CD40, and CD86, lack the Langerin and CD14 markers of Langerhans cells and monocytes, respectively, and to a significant extent express the DC maturation markers DC-LAMP and CD83. Treatment of psoriasis with efalizumab (antiCD11a, Raptiva) strongly reduces infiltration by these DCs in patients responding to this agent. Disease activity after therapy was more related to DC infiltrates and iNOS mRNA levels than T cell infiltrates, and CD11c ؉ cells responded more quickly to therapy than epidermal keratinocytes. Our results suggest that a type of DC, which resembles murine ''Tip-DCs'' that can accumulate during infection, has proinflammatory effects in psoriasis through nitric oxide and TNF-␣ production, and can be an important target for suppressive therapies.autoimmune disease ͉ CD11c ͉ Tip-DC

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“…In human tissues, both dermal and Langerhans DC express MHC class II and CD1a molecules, but only dermal DC express CD11b (22). These two types of tissue DC can be further differentiated by expression of Birbeck granules, Langerin, and E-cadherin on Langerhans cells and by expression of DC-SIGN on dermal DC.…”

Section: Discussionmentioning

confidence: 99%

Human BDCA-1-Positive Blood Dendritic Cells Differentiate into Phenotypically Distinct Immature and Mature Populations in the Absence of Exogenous Maturational Stimuli: Differentiation Failure in HIV Infection

Patterson

Donaghy

Amjadi

et al. 2005

The Journal of Immunology

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Current immunological opinion holds that myeloid dendritic cell (mDC) precursors migrate from the blood to the tissues, where they differentiate into immature dermal- and Langerhans-type dendritic cells (DC). Tissue DC require appropriate signals from pathogens or inflammatory cytokines to mature and migrate to secondary lymphoid tissue. We show that purified blood mDC cultured in vitro with GM-CSF and IL-4, but in the absence of added exogenous maturation stimuli, rapidly differentiate into two maturational and phenotypically distinct populations. The major population resembles immature dermal DC, being positive for CD11b, CD1a, and DC-specific ICAM-3-grabbing nonintegrin. They express moderate levels of MHC class II and low levels of costimulatory molecules. The second population is CD11b−/low and lacks CD1a and DC-specific ICAM-3-grabbing nonintegrin but expresses high levels of MHC class II and costimulatory molecules. Expression of CCR7 on the CD11b−/low population and absence on the CD11b+ cells further supports the view that these cells are mature and immature, respectively. Differentiation into mature and immature populations was not blocked by polymyxin B, an inhibitor of LPS. Neither population labeled for Langerin, E-cadherin, or CCR6 molecules expressed by Langerhans cells. Stimulation of 48-h cultured DC with LPS, CD40L, or poly(I:C) caused little increase in MHC or costimulatory molecule expression in the CD11b−/low DC but caused up-regulated expression in the CD11b+ cells. In HIV-infected individuals, there was a marked decrease in the viability of cultured blood mDC, a failure to differentiate into the two populations described for normal donors, and an impaired ability to stimulate T cell proliferation.

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In situ expression of the costimulatory molecules CD80 and CD86 on Langerhans cells and inflammatory dendritic epidermal cells (IDEC) in atopic dermatitis

Cited by 60 publications

References 27 publications

CTLA-4 Recombinant Protein Genetically Fused to Canine Fcε Receptor Iα Enhances Allergen Specific Lymphocyte Responses in Experimentally Sensitized Dogs

CTLA-4 Recombinant Protein Genetically Fused to Canine Fcε Receptor Iα Enhances Allergen Specific Lymphocyte Responses in Experimentally Sensitized Dogs

Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)

Human BDCA-1-Positive Blood Dendritic Cells Differentiate into Phenotypically Distinct Immature and Mature Populations in the Absence of Exogenous Maturational Stimuli: Differentiation Failure in HIV Infection

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In situ expression of the costimulatory molecules CD80 and CD86 on Langerhans cells and inflammatory dendritic epidermal cells (IDEC) in atopic dermatitis

Cited by 60 publications

References 27 publications

CTLA-4 Recombinant Protein Genetically Fused to Canine Fc&epsilon; Receptor I&alpha; Enhances Allergen Specific Lymphocyte Responses in Experimentally Sensitized Dogs

CTLA-4 Recombinant Protein Genetically Fused to Canine Fc&epsilon; Receptor I&alpha; Enhances Allergen Specific Lymphocyte Responses in Experimentally Sensitized Dogs

Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)

Human BDCA-1-Positive Blood Dendritic Cells Differentiate into Phenotypically Distinct Immature and Mature Populations in the Absence of Exogenous Maturational Stimuli: Differentiation Failure in HIV Infection

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CTLA-4 Recombinant Protein Genetically Fused to Canine Fcε Receptor Iα Enhances Allergen Specific Lymphocyte Responses in Experimentally Sensitized Dogs

CTLA-4 Recombinant Protein Genetically Fused to Canine Fcε Receptor Iα Enhances Allergen Specific Lymphocyte Responses in Experimentally Sensitized Dogs