Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease

Lancet. 2004 Feb 21;363(9409):608-15. doi: 10.1016/S0140-6736(04)15592-X.


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.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allergens / immunology*
  • CD4 Antigens / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / biosynthesis
  • Female
  • Flow Cytometry
  • Humans
  • Hypersensitivity / immunology*
  • Lymphocyte Activation / immunology*
  • Male
  • Middle Aged
  • Receptors, Interleukin-2 / immunology*
  • Suppressor Factors, Immunologic / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Helper-Inducer / immunology


  • Allergens
  • CD4 Antigens
  • Cytokines
  • Receptors, Interleukin-2
  • Suppressor Factors, Immunologic