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J Allergy Clin Immunol. 2019 Aug 8. pii: S0091-6749(19)31030-9. doi: 10.1016/j.jaci.2019.07.034. [Epub ahead of print]

T cell phenotypes are associated with serum IgE levels in Amish and Hutterite children.

Author information

1
Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.
2
Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
3
NIEHS Training Program in Environmental Toxicology, Graduate Program in Cellular and Molecular Medicine, Arizona Respiratory Center and Bio5 Institute, University of Arizona, Tucson, AZ 85712, Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ 85719, USA; Arizona Respiratory Center and Bio5 Institute, Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ.
4
Allergy and Asthma Consultants, Indianapolis, IN, USA.
5
Dr. von Hauner Children's Hospital, Ludwig Maximilians University Munich, Munich, Germany.
6
Department of Medicine, Section of Pulmonary and Critical Care Medicine, and the Committee on Immunology, University of Chicago, Chicago, IL 60637, USA. Electronic address: asperlin@uchicago.edu.

Abstract

OBJECTIVES:

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 lower asthma and atopy risk. Herein we investigated the T cell phenotypes in the same Amish and Hutterite children as in our earlier study to elucidate how this altered innate immunity effects adaptive T cells.

METHODS:

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 by allergen-specific and total IgE levels.

RESULTS:

Children exposed to Amish farms had increased activated Treg phenotypes, while conventional CD4 T cell expressed lower levels of co-stimulation molecules and other activation markers. The increase in circulating activated Tregs was associated with 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 Hutterite children (non-parametric t test p<0.0001), a difference that remained even after accounting for the effects of age and sex (conditional log regression exponential β=1.08, P=0.0053). The proportion of these cells correlated with high T cell IFNγ production (rs=0.573, P=0.005) and low serum IgE (rs=-0.417, P=0.025). Further, CD28null CD8 T cells were increased in Amish children with high expression of the innate genes TNF and TNFAIP3 in peripheral blood leukocytes.

CONCLUSION:

Amish children's blood leukocytes are not only altered in their innate immune status, but additionally have distinct T cell phenotypes that are often associated with increased antigenic exposure.

KEYWORDS:

Asthma; CD4 T cells; CD8 T cells; T cell activation; adaptive immunity; atopy

PMID:
31401285
DOI:
10.1016/j.jaci.2019.07.034
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