Ling EM, Smith T, Nguyen XD, et al. Lancet. 2004;363:608–615
Purpose of the Study.
The investigators proposed to determine if the amount of inhibition of allergic responses by CD4+CD25+ T cells was related to atopy and allergic disease.
Volunteers who were atopic (n = 12) or nonatopic (n = 9) or had hay fever (n = 11) were recruited by advertisement and from among hospital staff and allergy clinic patients.
Cells were isolated from atopic donors (positive serum-specific IgE or skin tests and a history of allergic symptoms), nonatopic donors (no history of allergic symptoms, negative skin-prick tests, and normal amounts of serum IgE), and patients with hay fever (rhinitis symptoms between June and August and positive skin-prick tests to grass pollen extract but not to other allergens). Peripheral blood mononuclear cells (PBMCs), CD4+CD25+ T cells, CD4+CD25− T cells, and 2:1 ratios of CD4+CD25− and CD4+CD25+ T cells were cultured for 6 days with cat dander, grass pollen, or medium alone (negative control). The supernatant was analyzed for cytokines, and incorporation of 3H-thymidine was used as an index of proliferation.
In allergen-driven cultures, CD4+CD25+ T cells from nonatopic donors showed little proliferation and suppressed CD4+CD25− T cell proliferation in a dose-dependent manner. CD4+CD25− T cells showed enhanced production of interleukin (IL)-5 compared with unseparated PBMCs (P = .0056). Compared with nonatopic individuals, suppression of allergen-driven proliferation of CD4+CD25− T cells by CD4+CD25+ T cells was lower in atopic patients (P = .012) and lowest in patients with hay fever who had active rhinitis (P = .0003). Suppression of IL-5 production was also lowest in patients with hay fever who had active rhinitis (P = .0166). When the patients with hay fever were studied outside of their allergy season, the suppression of proliferation was greater than during their allergy season but less than in nonatopic individuals (P = .0028) and similar to the atopic group.
In atopic individuals, especially those with active rhinitis symptoms, CD4+CD25+ regulatory T cells showed a decreased ability to regulate allergen-driven responses, compared with nonatopic individuals.
In vitro, the decreased suppression of allergen-driven responses by CD4+CD25+ regulatory T cells from atopic individuals supports the association between unchecked T-helper 2 responses and the development of atopy. As the authors suggested, mechanisms may include a deficiency in the regulatory activity of CD4+CD25+ T cells in atopic individuals or an activation and expansion of CD4+CD25− T cells in response to allergen exposure to a degree that overcomes the regulatory capacity of the CD4+CD25+ T cells. Although additional study will be necessary before these results can be applied clinically, augmentation of CD4+CD25+ T cell suppression of the T-helper 2 response may represent a future therapy for atopic disease.