Characterization of regulatory T cells in urban newborns

Abstract

Background

In the United States, asthma prevalence is particularly high among urban children. Although the underlying immune mechanism contributing to asthma has not been identified, having impaired T regulatory (Treg) cells at birth may be a determining factor in urban children. The objective of this study was to compare Treg phenotype and function in cord blood (CB) of newborns to those in peripheral blood (PB) of a subset of participating mothers.

Methods

Treg numbers, expression, and suppressive function were quantified in subjects recruited prenatally from neighborhoods where ≥ 20% of families have incomes below the poverty line. Proportion of Treg cells and expression of naïve (CD45RA) or activated (CD45RO, CD69, and HLA-DR) markers in CD4 ⁺T cells was measured by flow cytometry. Treg suppressive capacity was determined by quantifying PHA-stimulated lymphocyte proliferation in mononuclear cell samples with and without CD25 depletion.

Results

In an urban cohort of 119 newborns and 82 mothers, we found that newborns had similar number of cells expressing FOXP3 as compared to the mothers but had reduced numbers of CD4 ⁺CD25 ⁺bright cells that predominantly expressed the naïve (CD45RA) rather than the activated/memory (CD45RO) phenotype found in the mothers. Additionally, the newborns had reduced mononuclear cell TGF-β production, and reduced Treg suppression of PHA-stimulated lymphocyte proliferation compared to the mothers.

Conclusion

U.S. urban newborns have Treg cells that express FOXP3, albeit with an immature phenotype and function as compared to the mothers. Longitudinal follow-up is needed to delineate Treg cell maturation and subsequent risk for atopic diseases in this urban birth cohort.