Strömbeck A, Rabe H, Lundell A-C, Andersson K, Johansen S, Adlerberth I, Wold A E, Hesselmar B, Rudin A
Department of Rheumatology and Inflammation Research, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Clin Exp Allergy. 2014 Jul;44(7):940-52. doi: 10.1111/cea.12290.
The role of FOXP3(+) regulatory T cells in the prevention against sensitization and allergy development is controversial.
We followed 65 newborn Swedish children from farming and non-farming families from birth to 3 years of age and investigated the relation between CD4(+) T cell subsets in blood samples and development of sensitization and allergic disease.
The proportions of FOXP3(+) CD25(high) , CTLA-4(+) CD25(+) , CD45RO(+) , HLA-DR(+) , CCR4(+) or α4β7(+) within the CD4(+) T cell population were examined by flow cytometry of blood samples at several time-points. Mononuclear cells were isolated from blood and stimulated with birch allergen, ovalbumin or the mitogen PHA, and the levels of IL-1β, IL-6, TNF, IFN-γ, IL-5 and IL-13 were measured. A clinical evaluation regarding the presence of allergen-specific IgE and allergy was performed at 18 and 36 months of age.
Multivariate discriminant analysis revealed that children who were sensitized at 18 or 36 months of age had higher proportions of FOXP3(+) CD25(high) T cells at birth and at 3 days of life than children who remained non-sensitized, whereas allergy was unrelated to the neonatal proportions of these cells. The proportions of CTLA-4(+) CD25(+) T cells were unrelated to both sensitization and allergy. The association between higher proportions of FOXP3(+) CD25(high) T cells and sensitization persisted after exclusion of farmer's children. Finally, a farming environment was associated with lower proportions of FOXP3(+) CD25(high) T cells in early infancy and to a more prominent T cell memory conversion and cytokine production.
CONCLUSION & CLINICAL RELEVANCE: Our results indicate that high proportions of FOXP3(+) CD25(high) T cells in neonates are not protective against later sensitization or development of allergy.
FOXP3(+)调节性T细胞在预防致敏和过敏发生中的作用存在争议。
我们对65名来自瑞典务农和非务农家庭的新生儿从出生到3岁进行跟踪，调查血样中CD4(+)T细胞亚群与致敏和过敏性疾病发生之间的关系。
在多个时间点通过流式细胞术检测血样中CD4(+)T细胞群体内FOXP3(+)CD25(高)、CTLA-4(+)CD25(+)、CD45RO(+)、HLA-DR(+)、CCR4(+)或α4β7(+)的比例。从血液中分离单核细胞，用桦树过敏原、卵清蛋白或丝裂原PHA刺激，检测IL-1β、IL-6、TNF、IFN-γ、IL-5和IL-13的水平。在18个月和36个月时进行关于过敏原特异性IgE和过敏情况的临床评估。
多变量判别分析显示，在18个月或36个月时致敏的儿童在出生时和出生3天时FOXP3(+)CD25(高)T细胞的比例高于未致敏的儿童，而过敏与这些细胞的新生儿比例无关。CTLA-4(+)CD25(+)T细胞的比例与致敏和过敏均无关。排除农民家庭的儿童后，FOXP3(+)CD25(高)T细胞比例较高与致敏之间的关联依然存在。最后，务农环境与婴儿早期FOXP3(+)CD25(高)T细胞比例较低以及更显著的T细胞记忆转换和细胞因子产生有关。
我们的结果表明，新生儿中高比例的FOXP3(+)CD25(高)T细胞对后期致敏或过敏的发生并无保护作用。
