Immune regulation by CD4<sup>+</sup>CD25<sup>+</sup> T cells and interleukin‐10 in birch pollen‐allergic patients and non‐allergic controls

Thunberg, Sarah; Akdis, Miibeccel; Akdiş, Cezmi A.; Grönneberg, R.; Malmström, Vivianne; Trollmo, Christina; Hage, Marianne van; Gafvelin, Guro

doi:10.1111/j.1365-2222.2007.02739.x

Cited by 72 publications

(58 citation statements)

References 37 publications

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“…3), suggesting that the level of T cell regulation in atopic individuals in general is reduced. This is supported by studies in infants (6–18 months old) with atopic dermatitis stimulated with various antigens and allergens [36] as well as studies in birch pollen-allergic patients [35,37]. …”

Section: Discussionmentioning

confidence: 58%

“…However, Francis et al [6] did not find Phl p-induced TGF-β production in PBMC cultures from non-atopic or atopic donors. Moreover, blocking of TGF-β in PBMC from birch pollen-allergic patients did not influence Bet v 1-specific proliferation or cytokine production and had only a marginal effect on IFN-γ production in non-atopic controls [37]. This suggests that the involvement of TGF-β in the regulation of responses to allergens in non-SIT-treated allergic patients is minimal and the effect of TGF-β will not be discussed further.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionmentioning

confidence: 58%

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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“…To + Treg cells to suppress allergy-promoting Th2 cell proliferation and cytokine production than reduced cell numbers (50)(51)(52), SIT still could have an impact on the suppressive activity of Foxp3 + Treg cells. Bet v 1-specific Th2 cell responses remained largely unaffected during the first 12 mo of SIT, in contrast to other studies that reported a decrease in allergen-specific Th2 cells (53,54).…”

Section: Discussionmentioning

confidence: 99%

Birch Pollen Immunotherapy Leads to Differential Induction of Regulatory T Cells and Delayed Helper T Cell Immune Deviation

Möbs

Slotosch

Löffler

et al. 2010

The Journal of Immunology

120

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Correction of an imbalance between allergen-specific T cell subsets is considered a critical event in establishing allergen tolerance by specific immunotherapy (SIT). In a comprehensive, longitudinal study, distinct T cell populations and Ig subtypes were analyzed in subjects allergic to birch pollen during decisive time points of SIT (i.e., induction and maintenance phase), as well as in and out of birch pollen season. An increase in Bet v 1-specific, IL-10–secreting T cells, fulfilling the criteria of inducible type 1 regulatory T (Tr1) cells, was observed by the end of the induction phase; this resulted in a decreased ratio of allergen-specific IL-5+ Th2/Tr1 cells. In contrast, CD4+CD25+CD127low regulatory T cell numbers did not change. Furthermore, enhanced concentrations of allergen-specific IgG Abs were observed, whereas allergen-specific IgE and IgA levels remained unchanged. After 1 y of SIT, a reduced ratio of allergen-specific Th2/IFN-γ+ Th1 cells was apparent. Although untreated and SIT-treated allergic subjects developed enhanced Th2 cell responses during birch pollen season, only SIT-treated patients experienced elevated numbers of allergen-specific Tr1 cells, which were associated with reduced skin prick test reactivity and diminished clinical symptoms. In coculture assays, allergen-specific Tr1 cells showed an IL-10– and dose-dependent inhibition of CD4+CD25− T effector cells. Thus, SIT has differential effects on regulatory T cell subsets, resulting in an early induction of allergen-specific Tr1 cells associated with an increase in allergen-specific IgG, and it leads to a delayed shift from an allergen-specific Th2- to a Th1-dominated immune response.

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“…Mean purity of the CD4+ cells was 96% (95–98%) and for CD4+CD25+ cells 83% (66–94%) as determined by staining with anti-CD25-PE (Miltenyi Biotec), anti-CD4-FITC, IgG1-PE and IgG1-FITC (BD Pharmingen) and analysis on a FACSCalibur flow cytometer (BD Biosciences). A detailed description of the characterization of isolated Treg and Teffector cell fractions has been published elsewhere [24]. Cells in the CD4– fraction were irradiated (30 Gray) and used as antigen-presenting cells.…”

Section: Methodsmentioning

confidence: 99%

Low Levels of Endotoxin Enhance Allergen-Stimulated Proliferation and Reduce the Threshold for Activation in Human Peripheral Blood Cells

Veličković

Thunberg

Polović

et al. 2007

Int Arch Allergy Immunol

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Background: Endotoxins, comprised of bacterial cell wall lipopolysaccharides (LPS), have been reported to have both protective and exacerbating effects on the development and maintenance of allergic disease in humans and on markers of allergic inflammation in animal models of allergy. In this study, we investigated the effect of low concentrations of LPS on human peripheral blood mononuclear cells (PBMC) stimulated with the major cat allergen Fel d 1. Methods: Extensive purification of recombinant (r) Fel d 1 yielded essentially endotoxin-free rFel d 1 (0.2 ng LPS /mg protein). PBMCs prepared from 15 subjects having IgE to cat (>0.7 kU_A/l) and 8 subjects IgE negative to cat were stimulated with 2, 10 or 25 µg/ml of rFel d 1 in the presence or absence of 50 pg/ml LPS. Proliferation was measured after 7 days of culture and supernatants were analyzed for IFNγ, IL-5 and IL-10. Results: LPS (50 pg/ml) increased rFel d 1-stimulated proliferation of PBMCs both from subjects IgE-positive and subjects negative to cat allergens. PBMCs from 13 of the subjects did not proliferate in response to stimulation with 2 and 10 µg/ml rFel d 1 alone but did so in the presence of LPS. Moreover, LPS increased the levels of rFel d 1-stimulated IFNγ in cultures from cat-negative subjects, IL-5 from cat-positive subjects and IL-10 from both groups. Conclusion: Very low doses of LPS enhance proliferation and decrease the apparent threshold level for cell activation, prompting careful evaluation of allergen stimulated T cell activation in vitro.

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Immune regulation by CD4⁺CD25⁺ T cells and interleukin‐10 in birch pollen‐allergic patients and non‐allergic controls

Cited by 72 publications

References 37 publications

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

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

Birch Pollen Immunotherapy Leads to Differential Induction of Regulatory T Cells and Delayed Helper T Cell Immune Deviation

Low Levels of Endotoxin Enhance Allergen-Stimulated Proliferation and Reduce the Threshold for Activation in Human Peripheral Blood Cells

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Immune regulation by CD4+CD25+ T cells and interleukin‐10 in birch pollen‐allergic patients and non‐allergic controls

Cited by 72 publications

References 37 publications

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

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

Birch Pollen Immunotherapy Leads to Differential Induction of Regulatory T Cells and Delayed Helper T Cell Immune Deviation

Low Levels of Endotoxin Enhance Allergen-Stimulated Proliferation and Reduce the Threshold for Activation in Human Peripheral Blood Cells

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Product

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Immune regulation by CD4⁺CD25⁺ T cells and interleukin‐10 in birch pollen‐allergic patients and non‐allergic controls