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Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells.

Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, Thunberg S, Deniz G, Valenta R, Fiebig H, Kegel C, Disch R, Schmidt-Weber CB, Blaser K, Akdis CA - J. Exp. Med. (2004)

Bottom Line: Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4-secreting T cells in allergic individuals.Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-beta as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules.These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.

View Article: PubMed Central - PubMed

Affiliation: Swiss Institute of Allergy and Asthma Research, Obere Strasse 22, CH-7270 Davos. akdism@siaf.unizh.ch

ABSTRACT
The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-gamma-, interleukin (IL)-4-, and IL-10-producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1-like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4-secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-beta as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.

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Increased frequency of allergen-specific Tr1 cells in healthy individuals and Th2 cells in allergic individuals. (A) Frequency of Der p 1– and Bet v 1–specific, cytokine-secreting CD4+ T cells from eight allergic individuals and Cor a 1–, Bet v 1-, Der p 1–, and Pyr c 5–specific, cytokine-secreting CD4+ T cells from 15 healthy individuals out of pollen season. (B) Frequency of Der p 1–specific T cells in six allergic and six healthy, and Bet v 1–specific T cells in three allergic and three healthy individuals by ELISPOT assay. *, P < 0.01; **, P < 0.001.
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fig3: Increased frequency of allergen-specific Tr1 cells in healthy individuals and Th2 cells in allergic individuals. (A) Frequency of Der p 1– and Bet v 1–specific, cytokine-secreting CD4+ T cells from eight allergic individuals and Cor a 1–, Bet v 1-, Der p 1–, and Pyr c 5–specific, cytokine-secreting CD4+ T cells from 15 healthy individuals out of pollen season. (B) Frequency of Der p 1–specific T cells in six allergic and six healthy, and Bet v 1–specific T cells in three allergic and three healthy individuals by ELISPOT assay. *, P < 0.01; **, P < 0.001.

Mentions: As it was possible to purify single allergen-specific Th1-, Th2-, and Tr1-like cells, their frequency and functional properties were investigated in the next step. The frequency of T cell subsets specific to different mucosal allergens was compared in healthy and allergic individuals using two different techniques. Recombinant major allergens of house dust mite (Der p 1) and birch pollen (Bet v 1) were used as aeroallergens, and pear (Pyr c 5) and hazelnut (Cor a 1) were used as food antigens to analyze the frequency of specific Th1-, Th2-, and Tr1-like cells. Although specific T cells that belong to all three subsets were detectable in both healthy and allergic individuals, allergen-specific IL-10–secreting T cells were the predominant subset in healthy individuals. We found similar results for each allergen. In contrast, an increased frequency of IL-4–secreting T cells was observed in allergic patients (Fig. 3 A). ELISPOT was used as an alternative method in allergen-stimulated PBMC cultures and demonstrated a similar frequency distribution of Der p 1– and Bet v 1–specific T cell subsets (Fig. 3 B).


Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells.

Akdis M, Verhagen J, Taylor A, Karamloo F, Karagiannidis C, Crameri R, Thunberg S, Deniz G, Valenta R, Fiebig H, Kegel C, Disch R, Schmidt-Weber CB, Blaser K, Akdis CA - J. Exp. Med. (2004)

Increased frequency of allergen-specific Tr1 cells in healthy individuals and Th2 cells in allergic individuals. (A) Frequency of Der p 1– and Bet v 1–specific, cytokine-secreting CD4+ T cells from eight allergic individuals and Cor a 1–, Bet v 1-, Der p 1–, and Pyr c 5–specific, cytokine-secreting CD4+ T cells from 15 healthy individuals out of pollen season. (B) Frequency of Der p 1–specific T cells in six allergic and six healthy, and Bet v 1–specific T cells in three allergic and three healthy individuals by ELISPOT assay. *, P < 0.01; **, P < 0.001.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211782&req=5

fig3: Increased frequency of allergen-specific Tr1 cells in healthy individuals and Th2 cells in allergic individuals. (A) Frequency of Der p 1– and Bet v 1–specific, cytokine-secreting CD4+ T cells from eight allergic individuals and Cor a 1–, Bet v 1-, Der p 1–, and Pyr c 5–specific, cytokine-secreting CD4+ T cells from 15 healthy individuals out of pollen season. (B) Frequency of Der p 1–specific T cells in six allergic and six healthy, and Bet v 1–specific T cells in three allergic and three healthy individuals by ELISPOT assay. *, P < 0.01; **, P < 0.001.
Mentions: As it was possible to purify single allergen-specific Th1-, Th2-, and Tr1-like cells, their frequency and functional properties were investigated in the next step. The frequency of T cell subsets specific to different mucosal allergens was compared in healthy and allergic individuals using two different techniques. Recombinant major allergens of house dust mite (Der p 1) and birch pollen (Bet v 1) were used as aeroallergens, and pear (Pyr c 5) and hazelnut (Cor a 1) were used as food antigens to analyze the frequency of specific Th1-, Th2-, and Tr1-like cells. Although specific T cells that belong to all three subsets were detectable in both healthy and allergic individuals, allergen-specific IL-10–secreting T cells were the predominant subset in healthy individuals. We found similar results for each allergen. In contrast, an increased frequency of IL-4–secreting T cells was observed in allergic patients (Fig. 3 A). ELISPOT was used as an alternative method in allergen-stimulated PBMC cultures and demonstrated a similar frequency distribution of Der p 1– and Bet v 1–specific T cell subsets (Fig. 3 B).

Bottom Line: Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4-secreting T cells in allergic individuals.Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-beta as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules.These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.

View Article: PubMed Central - PubMed

Affiliation: Swiss Institute of Allergy and Asthma Research, Obere Strasse 22, CH-7270 Davos. akdism@siaf.unizh.ch

ABSTRACT
The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-gamma-, interleukin (IL)-4-, and IL-10-producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1-like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4-secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-beta as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.

Show MeSH
Related in: MedlinePlus