T-cell phenotypes are associated with serum IgE levels in Amish and Hutterite children
Authors: Cara L. Hrusch, Michelle M. Stein, Justyna Gozdz, Mark Holbreich, Erika von Mutius, Donata Vercelli, Carole Ober, Anne I. Sperling
Journal: Journal of Allergy and Clinical Immunology (2019)

ObjectivesAmish children raised on traditional farms have lower atopy and asthma risk than Hutterite children raised on modern farms. In our previous study we established that the Amish environment affects the innate immune response to decrease asthma and atopy risk. Here we investigated T-cell phenotypes in the same Amish and Hutterite children as in our earlier study to elucidate how this altered innate immunity affects adaptive T cells.MethodsBlood was collected from 30 Amish and 30 Hutterite age- and sex-matched children; cells were cryopreserved until analysis. Flow cytometry was used to analyze cell subsets. Atopy was determined based on allergen-specific and total IgE levels.ResultsChildren exposed to Amish farms had increased activated regulatory CD4+ T-cell phenotypes, whereas conventional CD4 T cells expressed lower levels of costimulation molecules and other activation markers. The increase in numbers of circulating activated regulatory CD4+ T cells was associated with an increase in inhibitory receptors on monocytes in Amish, but not Hutterite, children. Strikingly, the Amish children had a higher proportion of CD28null CD8 T cells than the Hutterite children (P < .0001, nonparametric t test), a difference that remained even after accounting for the effects of age and sex (conditional log regression exponential β = 1.08, P = .0053). The proportion of these cells correlated with high T-cell IFN-γ production (rs = 0.573, P = .005) and low serum IgE levels (rs = −0.417, P = .025). Furthermore, CD28null CD8 T-cell numbers were increased in Amish children, with high expression of the innate genes TNF and TNF-α–induced protein 3 (TNFAIP3) in peripheral blood leukocytes.ConclusionAmish children's blood leukocytes are not only altered in their innate immune status but also have distinct T-cell phenotypes that are often associated with increased antigen exposure. Amish children raised on traditional farms have lower atopy and asthma risk than Hutterite children raised on modern farms. In our previous study we established that the Amish environment affects the innate immune response to decrease asthma and atopy risk. Here we investigated T-cell phenotypes in the same Amish and Hutterite children as in our earlier study to elucidate how this altered innate immunity affects adaptive T cells. Blood was collected from 30 Amish and 30 Hutterite age- and sex-matched children; cells were cryopreserved until analysis. Flow cytometry was used to analyze cell subsets. Atopy was determined based on allergen-specific and total IgE levels. Children exposed to Amish farms had increased activated regulatory CD4+ T-cell phenotypes, whereas conventional CD4 T cells expressed lower levels of costimulation molecules and other activation markers. The increase in numbers of circulating activated regulatory CD4+ T cells was associated with an increase in inhibitory receptors on monocytes in Amish, but not Hutterite, children. Strikingly, the Amish children had a higher proportion of CD28null CD8 T cells than the Hutterite children (P < .0001, nonparametric t test), a difference that remained even after accounting for the effects of age and sex (conditional log regression exponential β = 1.08, P = .0053). The proportion of these cells correlated with high T-cell IFN-γ production (rs = 0.573, P = .005) and low serum IgE levels (rs = −0.417, P = .025). Furthermore, CD28null CD8 T-cell numbers were increased in Amish children, with high expression of the innate genes TNF and TNF-α–induced protein 3 (TNFAIP3) in peripheral blood leukocytes. Amish children's blood leukocytes are not only altered in their innate immune status but also have distinct T-cell phenotypes that are often associated with increased antigen exposure.