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