Analysis of CD25hiCD4+ “regulatory” T-cell subtypes in atopic dermatitis reveals a novel TH2-like population

Reefer, A.J.; Satinover, S.M.; Solga, Michael D.; Lannigan, Joanne; Nguyen, Jennifer; Wilson, Barbara B.; Woodfolk, Judith A.

doi:10.1016/j.jaci.2007.11.003

Cited by 78 publications

(83 citation statements)

References 28 publications

(32 reference statements)

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“…En estas poblaciones celulares se encuentran células T reguladoras naturales, en las cuales se ha descrito actividad en enfermedades alérgicas como la dermatitis atópica (17). Otras poblaciones de células T reguladoras inducidas por el estímulo antigénico, se caracterizan por la secreción de citocinas reguladoras de la respuesta inmunitaria, como IL-10 o factor beta de crecimiento transformador (TGF-β) (18).…”

Section: Discussionunclassified

Expresión de IL-10, IL-4 e IFN-γ en lesiones activas de piel en niños con urticaria papular por picadura de pulga

et al. 2011

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El trabajo se realizó en la Fundación Santa Fe de Bogotá y la Universidad de los Andes.Introducción. La urticaria papular por picadura de pulga se conoce como una enfermedad alérgica. Sin embargo, las investigaciones no muestran una clara relación con las enfermedades alérgicas. Objetivo. Estudiar la expresión de IL-10, IL-4 e IFN-γ, como marcadores de la respuesta efectora de células T en lesiones de piel de pacientes con urticaria papular por picadura de pulga. Materiales y métodos. Se incluyeron 14 biopsias de lesiones de piel de niños con diagnóstico de urticaria papular por picadura de pulga y 5 biopsias de piel sana obtenidas de niños sometidos a cirugía por enfermedades no inflamatorias. Todas las muestras se obtuvieron de niños menores de 12 años. Se extrajo ARN con trizol y se cuantificaron los niveles de expresión de las citocinas con la técnica de reacción en cadena de la polimerasa en tiempo real. Resultados. En los pacientes con urticaria papular por picadura de pulga, se encontró amplia diversidad en los niveles de expresión de IFN-γ e IL-10, y valores bajos constantes para IL-4. Se observaron tres perfiles que no corresponden a un patrón común en los pacientes. Las muestras obtenidas de tejidos sanos no presentaron expresión de las citocinas. Conclusiones. Los datos corresponden a la primera descripción de citocinas que median la respuesta inmunitaria en el sitio de la lesión cutánea en niños con con urticaria papular por picadura de pulga, lo cual indica que la respuesta local es mixta ya que no se encuentra predominio de un fenotipo específico en ninguno de los pacientes.Palabras clave: urticaria, citocinas, interleucina-4, interleucina-10, interferón gamma. Expression of IL-10, IL-4 and IFN-γ in active skin lesions of children with papular urticaria

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Section: Discussionunclassified

Expresión de IL-10, IL-4 e IFN-γ en lesiones activas de piel en niños con urticaria papular por picadura de pulga

et al. 2011

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“…A direct link between the CD4 + CD25 + CCR4 +/– or CLA +/– T cells and regulation could have been obtained by further phenotypic characterization of the cells including staining for IL-10, Fox p 3 or CD127 or by functional analyses of isolated subpopulations. Such experiments were performed by Reefer et al [43], who demonstrated that CD4 + CD25 + CCR4 + T cells were increased in AD patients, and the percentage of these cells was linked to the severity of disease. Moreover, within this population cells expressing additional markers of regulatory T cells, Fox p 3 and GITR were increased and co-expression of CCR4 and CLA was also demonstrated, suggesting that both these receptors are related to T cell regulation [43].…”

Section: Discussionmentioning

confidence: 99%

“…Such experiments were performed by Reefer et al [43], who demonstrated that CD4 + CD25 + CCR4 + T cells were increased in AD patients, and the percentage of these cells was linked to the severity of disease. Moreover, within this population cells expressing additional markers of regulatory T cells, Fox p 3 and GITR were increased and co-expression of CCR4 and CLA was also demonstrated, suggesting that both these receptors are related to T cell regulation [43]. In line with this, Nguyen et al [44] and Ahern et al [45] demonstrated most recently that expression of CCR4 (as well as CCR8) is linked to CD4 + CD25 + T cell with regulatory properties and that CCR4-CCL17/22 signaling is intact in allergic patients, in contrast to CCR8-CCL1 signaling, which seems to be compromised in severely diseased patients.…”

Section: Discussionmentioning

confidence: 99%

The T Cell Response to Major Grass Allergens Is Regulated and Includes IL-10 Production in Atopic but Not in Non-Atopic Subjects

Domdey

Liu²,

Millner³

et al. 2010

Int Arch Allergy Immunol

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Background: The incidence of allergic diseases is increasing in industrialized countries and the immunological mechanisms leading to tolerance or allergy are poorly understood. Cytokines with suppressive abilities and CD4⁺CD25⁺ regulatory T cells have been suggested to play a central role in allergen-specific responses. The aim was to determine whether major grass allergens induce production of suppressive cytokines in allergic and healthy subjects and to examine the inhibitory effect of these cytokines on allergic responses. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy and grass-allergic donors and stimulated with the major grass allergens Phl p 1 or Phl p 5. The effects of endogenous IL-10 and/or TGF-β on proliferation and cytokine production were determined by use of blocking antibodies. In addition, the number of CD4⁺CD25⁺ T cells and their expression of chemokine receptors were investigated by flow cytometry. Results: Phl p 1 and Phl p 5 induced IL-10 production, which down-regulated proliferation and cytokine production, in PBMC cultures from atopic but not from non-atopic donors. Comparable frequencies of CD4⁺CD25⁺ T cells were present in PBMCs in the two groups, but fewer cells from atopic donors were CD4⁺CD25⁺CCR4⁺ and more cells were CD4⁺CD25⁺CLA⁺ compared to healthy donors. Conclusion:Allergen-specific responses of grass allergic patients but not in non-atopic subjects are influenced by regulatory cytokines produced in response to the important allergens. Differences in CD4⁺CD25⁺ T cell expression of chemokine receptors in allergic compared to non-atopic donors could suggest that the homing of CD4⁺CD25⁺ T cells is important for the regulation of allergen-specific responses.

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“…Several different subpopulations of CD4 + CD25 + T cells including CD4 + CD25 high have been evaluated in the past [12,24]. A positive relationship between this cell type and allergen-specific IgE has been seen, as well as suggestion of T H 2-promoting effects [12,24].…”

Section: Discussionmentioning

confidence: 99%

Temporal Dynamic Changes of Phenotypic Expression of Peripheral CD4 Cells during Environmental Allergen Challenge in an Experimental Model of Canine Atopic Dermatitis: A Pilot Study

Simpson

Maeda

Marsella

2009

The Journal of Veterinary Medical Science

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ABSTRACT. The immunopathology behind atopic dermatitis (AD) involves a myriad of inflammatory cells and their mediators. Thymus and activation-regulated chemokine (TARC) plays a significant role in the inflammatory phase by recruiting CCR4 + T H 2 cells. In addition, CD25 + activated T cells further propagate the allergic response after sensitization by producing cytokines. The purpose of this pilot study was to evaluate how exposure to a common allergen (house dust mite, HDM) would affect the proportions of circulating CD4 + CCR4 + T H 2 cells and CD4 + CD25 + activated T cells in an experimental model of AD using high-IgE Beagles. In this experimental model, previously sensitized Beagles develop lesions and pruritus upon allergen challenge consisting of 3-day environmental exposure, 3 hours/day. Blood samples were obtained before, during, and after the end of challenge (days 0, 2, 4, and 17). Clinical signs were evaluated and scored at the same time points. Peripheral blood mononuclear cells (PBMCs) were isolated and used for flow cytometry to identify proportions of CD4 + cells positive for either CCR4 or CD25 receptors. Both CD4 + cell types (CD25 + and CCR4 + ) peaked at day 17, when clinical signs had resolved. It is proposed that the increase of circulating CD4 + CCR4 + and CD4 + CD25 + cells most likely demonstrates the sensitization status of atopic individuals after environmental allergen challenge. Understanding of these two cell types could prompt additional research concerning therapeutic drugs for AD.KEY WORDS: activated T cells, atopic dermatitis, canine, CD4, CD25.

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Analysis of CD25hiCD4+ “regulatory” T-cell subtypes in atopic dermatitis reveals a novel TH2-like population

Cited by 78 publications

References 28 publications

Expresión de IL-10, IL-4 e IFN-γ en lesiones activas de piel en niños con urticaria papular por picadura de pulga

Expresión de IL-10, IL-4 e IFN-γ en lesiones activas de piel en niños con urticaria papular por picadura de pulga

The T Cell Response to Major Grass Allergens Is Regulated and Includes IL-10 Production in Atopic but Not in Non-Atopic Subjects

Temporal Dynamic Changes of Phenotypic Expression of Peripheral CD4 Cells during Environmental Allergen Challenge in an Experimental Model of Canine Atopic Dermatitis: A Pilot Study

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