Topical Superantigen Exposure Induces Epidermal Accumulation of CD8+ T Cells, a Mixed Th1/Th2-Type Dermatitis and Vigorous Production of IgE Antibodies in the Murine Model of Atopic Dermatitis

Savinko, Terhi; Lauerma, Antti; Lehtimäki, Sari; Gombert, Michael; Majuri, Marja Leena; Fyhrquist, Nanna; Dieu-Nosjean, Marie Caroline; Kemény, Lajos; Wolff, Henrik; Homey, Bernhard; Alenius, Harri

doi:10.4049/jimmunol.175.12.8320

Cited by 76 publications

(86 citation statements)

References 40 publications

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“…Our data are reminiscent to previous studies in human AD showing that, although CD4 ϩ T cells predominated in AD skin lesions, T cells infiltrating the epidermis were almost exclusively CD8 ϩ T cells (12). Along these lines, studies in mouse models of AD reported that allergen challenge is associated with epidermal recruitment of CD8 ϩ T cells (25), which is dramatically enhanced by coexposure to the superantigen staphylococcal enterotoxin B (26). However, only a few CD8 ϩ T cells, compared with CD4 ϩ T cells, were detected in the skin in these studies probably because of the time at which T cell infiltration was analyzed.…”

Section: Discussionsupporting

confidence: 63%

Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions

Hennino

Vocanson

Toussaint

et al. 2007

The Journal of Immunology

103

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Skin lesions in the allergic form of atopic dermatitis (AD) are induced by allergen-specific T cells that infiltrate the skin at the site of allergen exposure. Although Th2-type CD4+ T cells appear to be crucial in AD pathophysiology, little is known about the contribution of CD8+ T cells in the development of the allergic skin inflammation. In the present study, we have analyzed the respective role of CD8+ and CD4+ T cells in the development of AD skin lesions in a mouse model of allergen-induced AD. In sensitized mice, CD8+ T cells are rapidly and transiently recruited to the allergen-exposed site and initiate the inflammatory process leading to skin infiltration with eosinophils and Th1/Th2-producing cells. CD8+ T cell-depleted mice show no inflammation, demonstrating that these cells are mandatory for the development of AD. In contrast, CD4+ T cell-depleted mice develop a severe form of eczema. Furthermore, adoptive transfer of CD8+ T cells from sensitized mice into naive recipient mice leads to skin inflammation soon after allergen exposure. These data indicate that allergen-primed CD8+ T cells are required for the development of AD-like lesions in mice.

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Section: Discussionsupporting

confidence: 63%

Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions

Hennino

Vocanson

Toussaint

et al. 2007

The Journal of Immunology

103

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“…The colonization of S. aureus on the skin plays an important part in the pathology of AD [16,17,18,19]. Various staphylococcal superantigens have been analyzed for their potential to intensify AD or other skin diseases [16,20,21].…”

Section: Discussionmentioning

confidence: 99%

Clinical Features and Immunological Markers of Atopic Dermatitis in Elderly Patients

Bożek¹,

Fisher²,

Filipowska³

et al. 2011

Int Arch Allergy Immunol

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Background: Atopic dermatitis (AD) is increasing among the elderly. Staphylococcus aureus colonization is one of the most important aggravating factors in AD. Objective: This study analyses the clinical features of AD in elderly patients and determines the pathogenic roles of staphylococcal superantigens in AD with low and high total IgE levels. Methods:S. aureus enterotoxin genes were evaluated using PCR. Additionally, S. aureus-specific IgE levels and peripheral blood lymphocyte profiles were assessed. Results: A total of 44 women and 77 men diagnosed with AD with a mean age of 68.92 ± 6.51 years were evaluated. In 17 (68%) patients with AD and low levels of total IgE, there was a positive correlation between the positive results for enterotoxin B, S. aureus-specific IgE antibodies and Th1 cytokine profiles (Spearman’s rank correlation test, r = 0.89, p < 0.05). Conclusion: Our results indicate that AD patients with low total IgE levels differ in immunopathogenesis from AD patients with high circulating levels of total IgE AD.

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“…Staphylococcal superantigen has been documented to reduce regulatory T cell activity in humans (22) and to confer T cell steroid resistance (23), but these studies have not examined the influence of superantigen on allergen-specific T cell responses. A murine study showed that combined staphylococcal enterotoxin B (SEB) and ovalbumin application to the skin increased ovalbumin-specific IgE, but again the role of specific T cells has not been addressed (24). Using house dust mite-derived Der p 1 as the model allergen, we sought to test the hypothesis that S. aureus superantigen influences the allergenspecific T cell response.…”

Section: Atopy ͉ T Cells ͉ Keratinocytes ͉ Staphylococcusmentioning

confidence: 99%

Bacterial superantigen facilitates epithelial presentation of allergen to T helper 2 cells

Ardern‐Jones

Black

Bateman

et al. 2007

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

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Although clinical and laboratory evidence support roles for both staphylococcal infection and environmental allergens in the pathogenesis of atopic dermatitis, human studies have largely considered these variables independently. We sought to test the hypothesis that staphylococcal superantigen influences the allergen-specific T cell response. We first mapped a Der p 1 epitope and used HLA DRB1*1501 class II tetramer-based cell sorted populations to show that specific CD4 ؉ T cells were able to recognize the peptide presented by HLA DR-matched keratinocytes. We observed that staphylococcal enterotoxin B (SEB) enhanced the IL-4 Der p 1-specific T cell response. This response was mediated by two synergistic mechanisms: first, SEB-induced IFN-␥ promoted class II and intercellular adhesion molecule-1 expression by presenting keratinocytes; and second, SEB-induced IL-4 directly amplified allergen-specific CD4 ؉ T cell production of many cytokines. We propose that handling of staphylococcal infection is a critical step in the amplification of the allergen-specific T cell response, linking two common disease associations and with implications for the prevention and treatment of atopic disease.T here is convincing evidence that allergic reactivity to environmental challenge has a role in the pathogenesis of atopic dermatitis (AD). For example, the histology of AD shares many features with classic allergic contact delayed-type hypersensitivity, including spongiosis and a dominant T cell inflammatory infiltrate that is distributed predominantly in a dermal, and to a lesser extent epidermal pattern. Approximately 80% of individuals with AD have circulating specific IgE recognizing one or more of house dust mite, cat, dog, grass, and other ubiquitous environmental allergens (1). In many studies, allergen-specific CD4 ϩ and CD8 ϩ T cells have been documented to be present in the peripheral blood and lesional skin of affected individuals and to produce diverse cytokines but with a frequent T helper 2 (Th2) dominance (2, 3). House dust mite extract application to the skin of individuals with AD can reproduce eczematous changes (4, 5), and allergen avoidance has been shown by some to be partially effective (6, 7). Keratinocytes have been shown to up-regulate HLA class II and intercellular adhesion molecule-1 (ICAM-1) in AD and other inflammatory dermatoses (8, 9) and also in response to injection of IFN-␥ into normal skin (10). However, in isolation, allergic reactivity to an environmental challenge does not explain all of the features of AD. Twenty percent of affected individuals do not generate IgE responses to such ubiquitous proteins, and it is unclear why disease incidence changes during age and between different geographical regions. The risk of disease is clearly influenced by genetic susceptibility factors, some of which affect the immune response, e.g., polymorphisms of the Fc R1 and IL-4R genes (11-13). However, it is becoming increasingly clear from the genetic studies that skin-specific genes, determining variables s...

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Topical Superantigen Exposure Induces Epidermal Accumulation of CD8+ T Cells, a Mixed Th1/Th2-Type Dermatitis and Vigorous Production of IgE Antibodies in the Murine Model of Atopic Dermatitis

Cited by 76 publications

References 40 publications

Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions

Skin-Infiltrating CD8+ T Cells Initiate Atopic Dermatitis Lesions

Clinical Features and Immunological Markers of Atopic Dermatitis in Elderly Patients

Bacterial superantigen facilitates epithelial presentation of allergen to T helper 2 cells

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