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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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Expression of suppressor molecules on IL-10–secreting T cells. (A) Immediately after purification, antigen-specific IL-10–secreting T cells of healthy individuals were analyzed for intracytoplasmic IL-10, surface IL-10R, CTLA-4, CD25, and PD-1 by flow cytometry. Data are compared with CD3+ T cells of the same donor stimulated with the same antigen. (B) TGF-β RI and RII expression by immunohistology. (A and B) Same results were obtained in three independent experiments.
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fig5: Expression of suppressor molecules on IL-10–secreting T cells. (A) Immediately after purification, antigen-specific IL-10–secreting T cells of healthy individuals were analyzed for intracytoplasmic IL-10, surface IL-10R, CTLA-4, CD25, and PD-1 by flow cytometry. Data are compared with CD3+ T cells of the same donor stimulated with the same antigen. (B) TGF-β RI and RII expression by immunohistology. (A and B) Same results were obtained in three independent experiments.

Mentions: Molecules that may play a role on suppressive mechanisms of allergen-specific IL-10–secreting T cells were analyzed on freshly purified cells (Fig. 5). IL-10–secreting T cells expressed high amounts of IL-10, IL-10Rα chain, TGF-β receptors I and II, CTLA-4, CD25, and PD-1, suggesting that multiple suppressor factors may play a role on suppression of allergen-specific Th2 cells by Tr1 cells in healthy individuals.


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)

Expression of suppressor molecules on IL-10–secreting T cells. (A) Immediately after purification, antigen-specific IL-10–secreting T cells of healthy individuals were analyzed for intracytoplasmic IL-10, surface IL-10R, CTLA-4, CD25, and PD-1 by flow cytometry. Data are compared with CD3+ T cells of the same donor stimulated with the same antigen. (B) TGF-β RI and RII expression by immunohistology. (A and B) Same results were obtained in three independent experiments.
© Copyright Policy
Related In: Results  -  Collection

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

fig5: Expression of suppressor molecules on IL-10–secreting T cells. (A) Immediately after purification, antigen-specific IL-10–secreting T cells of healthy individuals were analyzed for intracytoplasmic IL-10, surface IL-10R, CTLA-4, CD25, and PD-1 by flow cytometry. Data are compared with CD3+ T cells of the same donor stimulated with the same antigen. (B) TGF-β RI and RII expression by immunohistology. (A and B) Same results were obtained in three independent experiments.
Mentions: Molecules that may play a role on suppressive mechanisms of allergen-specific IL-10–secreting T cells were analyzed on freshly purified cells (Fig. 5). IL-10–secreting T cells expressed high amounts of IL-10, IL-10Rα chain, TGF-β receptors I and II, CTLA-4, CD25, and PD-1, suggesting that multiple suppressor factors may play a role on suppression of allergen-specific Th2 cells by Tr1 cells in healthy individuals.

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