Relation of CD4+ CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease
EM Ling, T Smith, XD Nguyen, C Pridgeon, M Dallman… - The Lancet, 2004 - thelancet.com
EM Ling, T Smith, XD Nguyen, C Pridgeon, M Dallman, J Arbery, VA Carr, DS Robinson
The Lancet, 2004•thelancet.comBackground 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+
Tcells 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 …
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+
Tcells 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 …
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+ Tcells 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.
Findings
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.
Interpretation
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.
thelancet.com