Reduced IL-2 response from peripheral blood mononuclear cells exposed to bacteria at 6 months of age is associated with elevated total-IgE and allergic rhinitis during the first 7 years of life

Background: Autoimmunity and allergy have been associated with decreased number and function of regulatory T-cells (Tregs)and low interleukin-2 (IL-2)levels. We aimed to investigate if the release of IL-2 from peripheral blood mononuclear cells (PBMCs)stimulated with pathogenic airway bacteria was associated with development of allergy-outcomes in early childhood. Methods: PBMCs were isolated at age 6 months in 331 infants from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC₂₀₀₀)mother-child cohort, and subsequently stimulated with H. influenzae, M. catarrhalis and S. pneumoniae in in vitro cultures. Levels of cytokines (IL-2, IL-10, IFN-γ, TNF-α, IL-5, IL-13 and IL-17A)were determined in the supernatant by electrochemiluminescence immunoassays. The immune profiles were analyzed for association with development of total-IgE, allergic sensitization and rhinitis during the first 7 years of life using regression models and principal component analysis (PCA). Findings: An attenuated IL-2 response to stimulation with H. influenzae (p = 0∙011)and M. catarrhalis (p = 0∙027)was associated with elevated total-IgE at age 7, which was confirmed in a multivariate PCA model including all cytokine measurements (PC2, p = 0∙032). An immune profile with both reduced IL-2 and elevated IL-5 was associated with increased risk of allergic rhinitis (PC3, p = 0∙038). We found no associations with development of allergic sensitization. Interpretation: A reduced IL-2 response from PBMCs exposed to common pathogenic airway bacteria at age 6 months was associated with elevated total-IgE and allergic rhinitis during the first 7 years of life. These findings suggest that suppressed Treg activity in early life may herald onset of allergy in early childhood, which could be a target for low-dose IL-2 trials in the future. Fund: COPSAC is funded by private and public research funds all listed on www.copsac.com.