Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells.
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.
Akdis
Mübeccel
M
Swiss Institute of Allergy and Asthma Research, Obere Strasse 22, CH-7270 Davos. akdism@siaf.unizh.ch
Verhagen
Johan
J
Taylor
Alison
A
Karamloo
Fariba
F
Karagiannidis
Christian
C
Crameri
Reto
R
Thunberg
Sarah
S
Deniz
Günnur
G
Valenta
Rudolf
R
Fiebig
Helmut
H
Kegel
Christian
C
Disch
Rainer
R
Schmidt-Weber
Carsten B
CB
Blaser
Kurt
K
Akdis
Cezmi A
CA
D000328:Adult; D000485:Allergens / Q000276:immunology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D060908:CTLA-4 Antigen; D006801:Humans; D006967:Hypersensitivity / Q000209:etiology / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D000485:Allergens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma