Association between CD4⁺CD25^high T cells and atopy in children

Background: There is evidence that CD4⁺CD25^high T-regulatory cells are important for establishing tolerance to allergens, but information in children is limited. Objective: To test the hypothesis that greater numbers and function of CD4⁺CD25^high T cells are associated with a reduced risk of childhood allergies and wheezing. Methods: A cohort of 151 six-year-old children from atopic families was analyzed for peripheral blood CD4⁺CD25^high and CD4⁺CD25^int T cells by flow cytometry and for clinical and immunologic correlates of atopy. The associations between these variables were assessed by regression analysis. Results: Factors positively associated with % CD4⁺CD25^high/CD4 T cells were male sex, number of positive allergen-specific IgE tests, total IgE, season, and 1-month average total pollen count preceding blood draw. The percentage of CD4⁺CD25^high/total CD4 T cells did not correlate with induced cytokine production, and correlated negatively with suppressive capacity of CD4⁺CD25⁺ T cells (r = -0.45; P = .034). The percentage of CD4⁺CD25^int/CD4 T cells was 54% higher in pollen-sensitized children compared with nonsensitized children in spring (P = .023 for interaction), and correlated positively with IL-5, IL-10, and IL-13 (P ≤ .001 for all). Conclusion: Our findings suggest that blood CD4⁺CD25^high cells are a mixture of activated and regulatory T cells, and that these cells could be seasonally regulated by environmental factors such as pollen exposure. Clinical implications: Seasonal increases in CD4CD25^high expression in children with allergy may represent systemic immune activation caused by pollen exposures.