Department of Medicine, Section of Pulmonary and Critical Care Medicine, University of Chicago, Chicago, Ill.
Department of Human Genetics, University of Chicago, Chicago, Ill.
J Allergy Clin Immunol. 2019 Nov;144(5):1391-1401.e10. doi: 10.1016/j.jaci.2019.07.034. Epub 2019 Aug 8.
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 CD28 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 (r = 0.573, P = .005) and low serum IgE levels (r = -0.417, P = .025). Furthermore, CD28 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.
在传统农场中长大的阿米什儿童比在现代农场中长大的胡特尔特儿童患过敏和哮喘的风险更低。在我们之前的研究中,我们已经证实,阿米什环境会影响先天免疫反应,从而降低哮喘和过敏的风险。在这里,我们研究了与我们之前的研究相同的阿米什和胡特尔特儿童的 T 细胞表型,以阐明这种改变的先天免疫如何影响适应性 T 细胞。
从 30 名阿米什儿童和 30 名胡特尔特儿童中采集血液;细胞冷冻保存,直至分析。使用流式细胞术分析细胞亚群。根据过敏原特异性和总 IgE 水平确定过敏。
暴露于阿米什农场的儿童具有增加的活化调节性 CD4 T 细胞表型,而传统的 CD4 T 细胞表达较低水平的共刺激分子和其他活化标志物。循环活化调节性 CD4 T 细胞数量的增加与阿米什而非胡特尔特儿童单核细胞上抑制性受体的增加有关。引人注目的是,阿米什儿童的 CD28 CD8 T 细胞比例高于胡特尔特儿童(P < 0.0001,非参数 t 检验),即使在考虑年龄和性别影响后(条件对数回归指数β= 1.08,P = 0.0053),这种差异仍然存在。这些细胞的比例与高 T 细胞 IFN-γ 产生(r = 0.573,P = 0.005)和低血清 IgE 水平(r = -0.417,P = 0.025)相关。此外,在阿米什儿童中,CD28 CD8 T 细胞数量增加,外周血白细胞中先天基因 TNF 和 TNF-α诱导蛋白 3(TNFAIP3)的表达也增加。
阿米什儿童的血液白细胞不仅在其先天免疫状态上发生改变,而且具有明显的 T 细胞表型,这些表型通常与抗原暴露增加有关。