Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease.
BACKGROUND
Allergic diseases are frequent and rising in prevalence, and result from activation of T-helper (Th) 2 cells by allergens. CD4+CD25+ regulatory T cells suppress T-cell activation in vitro and prevent pathological findings in animal models of disease. We aimed to investigate whether the amount of inhibition of allergic responses by CD4+CD25+ T cells was related to atopy and allergic disease.


METHODS
Blood CD4+CD25+ and CD4+CD25- T cells were isolated from three groups of donors: non-atopic individuals; those atopic with no present symptoms; and patients with hayfever studied during and out of the grass-pollen season. We investigated the ability of CD25+ T cells from these donors to suppress allergen-stimulated T-cell proliferation and cytokine production in vitro.


RESULTS
CD4+CD25+ T cells from non-atopic donors suppressed proliferation and interleukin 5 production by their own allergen-stimulated CD4+CD25- T cells. Inhibition of proliferation by CD4+CD25+ T cells from atopic donors was significantly reduced (p=0.0012), and was even more diminished by CD4+CD25+ T cells isolated from patients with hayfever during the pollen season (p=0.0003). In patients with hayfever, out-of-season suppression remained less than that seen by regulatory cells from non-atopic donors.


CONCLUSIONS
Allergic disease can result from an inappropriate balance between allergen activation of regulatory CD4+CD25+ T cells and effector Th2 cells. This imbalance could result from a deficiency in suppression by regulatory T cells or strong activation signals could overcome such regulation. Treatment to enhance regulatory T-cell responses, in concert with reduction of Th2 cell activation, might be useful in prevention and treatment of allergic disease.
Department of Allergy, National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
Eleanor M
EM
Ling
Trevor
T
Smith
X Dao
XD
Nguyen
Carol
C
Pridgeon
Margaret
M
Dallman
Justine
J
Arbery
Victoria A
VA
Carr
Douglas S
DS
Robinson
D000328:Adult; D000485:Allergens / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013491:Suppressor Factors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000485:Allergens; D015704:CD4 Antigens; D016207:Cytokines; D015375:Receptors, Interleukin-2; D013491:Suppressor Factors, Immunologic