Recently activated infant CD25 + Th2 cells differ based on lifestyle and are associated with atopy

Background: Little is known about the ontogeny of T cell immunity during infancy in farming and urban lifestyle due to lack of immunophenotyping in such birth cohorts. Methods: Our study includes two birth cohorts (farming and urban) at differing risks and rates of allergic diseases. In this study, blood mononuclear cells were collected from infants at birth, and 6 and 12 months of age. We used full spectrum flow cytometry followed by traditional gating and the Scalable Weighted Iterative Flow-clustering Technique (SWIFT) high dimensional analysis to identify cell populations that differed between farming and urban infants. Additionally, we utilized RNAseq and Luminex to assess the function of the cell population of interest. Results: We identified several regulatory T cell (Treg) subpopulations elevated in farming lifestyle as well as in non-atopic infants. We also found a unique, recently activated effector memory CD25 CD127 CD161 CCR4 CRTH2 Th2 population that is elevated at 6 months in urban infants as well as infants who developed atopic dermatitis and/or food allergy and allergic sensitization. Functional assays confirmed this population to be highly Th2-skewed, as evidenced by an increase in Th2 cytokines and upregulation of pathways linked to asthma and Th2 differentiation. Conclusion: We have discovered Treg subpopulations associated with farming lifestyle and protection against allergic disease. We also describe a unique, recently activated effector memory Th2 population elevated in urban high-risk infants that is similar to the pathogenic effector Th2A cells but is CD25 and CD161 , potentially representing pre-Th2A cells implicated in the development of allergic disease.