A Phenotypically Distinct Human Th2 Cell Subpopulation Is Associated With Development of Allergic Disorders in Infancy.

Abstract

Background: Little is known about the ontogeny of T cell immunity during infancy in farming and urban lifestyles due to the lack of immunophenotyping in such birth cohorts.

Methods: Two birth cohorts (farming and urban) at differing risks and rates of allergic diseases were compared. Blood mononuclear cells were collected from infants at birth, and 6 and 12 months of age. Full spectrum flow cytometry, followed by traditional gating and the Scalable Weighted Iterative Flow-clustering Technique (SWIFT) high-dimensional analysis, were used to identify cell populations that differed between farming and urban infants. Additionally, single-cell RNAseq and multiplex cytokine assays were used to assess the function of cell populations of interest.

Results: Several regulatory T cell (Treg) subpopulations were elevated in farming lifestyles and in non-atopic infants. A unique effector memory CD25⁺CD127⁺CD161^-CD49d⁺CCR4⁺CRTH2⁺ Th2 population was elevated at 6 months in urban infants and in those who developed atopic dermatitis and/or food allergy and allergic sensitization. Although this population shared Th2 and IL-9 skewing with Th2A cells, the population uniquely failed to express CD161, produced more IL-2 and TNF-α, and upregulated the differentially expressed genes (DEGs), FOXP3 and the cytokine inducible SH2-containing protein gene (CISH) relative to Th2A cells. This population has been termed Th2B cells.

Conclusion: We describe a unique effector memory Th2 population elevated in urban high-risk infants, potentially implicated in the development of allergic disease.