Abstract:
The interpretation of clinical diagnostic results in suspected inborn errors of immunity, including Tregopathies, is hampered by the lack of age-stratified reference values for regulatory T cells (Treg) in the pediatric population and a consensus on which Treg immunophenotype to use. Regulatory B cells (Breg) are an important component of the regulatory system that have been poorly studied in the pediatric population. We analyzed (1) the correlation between the three immunophenotypic definitions of Treg (CD4+CD25hiCD127low, CD4+CD25hiCD127lowFoxP3+, CD4+CD25hiFoxP3+), and with CD4+CD25hi and (2) the changes in Treg and Breg frequencies and their maturation status with age. We performed peripheral blood immunophenotyping of Treg and Breg (CD19+CD24hiCD38hi) by flow cytometry in 55 healthy pediatric controls. We observed that Treg numbers varied depending on the definition used, and the frequency ranged between 3.3-9.7% for CD4+CD25hiCD127low, 0.07-1.6% for CD4+CD25hiCD127lowFoxP3+, and 0.24-2.83% for CD4+CD25hiFoxP3+. The correlation between the three definitions of Treg was positive for most age ranges, especially between the two intracellular panels and with CD4+CD25hi vs CD4+CD25hiCD127low. Treg and Breg frequencies tended to decline after 7 and 3 years onwards, respectively. Treg\'s maturation status increased with age, with a decline of naïve Treg and an increase in memory/effector Treg from age 7 onwards. Memory Breg increased progressively from age 3 onwards. In conclusion, the number of Treg frequencies spans a wide range depending on the immunophenotypic definition used despite a good level of correlation exists between them. The decline in numbers and maturation process with age occurs earlier in Breg than in Treg.
摘要:
对疑似先天性免疫错误的临床诊断结果的解释,包括Tregpathies,由于缺乏儿科人群中调节性T细胞(Treg)的年龄分层参考值以及使用Treg免疫表型的共识而受到阻碍。调节性B细胞(Breg)是调节系统的重要组成部分,在儿科人群中研究甚少。我们分析了(1)Treg(CD4+CD25hiCD127low,CD4+CD25hiCD127lowFoxP3+,CD4+CD25hiFoxP3+),以及CD4+CD25hi和(2)Treg和Breg频率及其成熟状态随年龄的变化。我们通过流式细胞术对55例健康儿科对照进行了Treg和Breg(CD19CD24hiCD38hi)的外周血免疫分型。我们观察到Treg数根据使用的定义而变化,CD4+CD25hiCD127low的频率在3.3-9.7%之间,CD4+CD25hiCD127lowFoxP3+0.07-1.6%,CD4+CD25hiFoxP3+为0.24-2.83%。Treg的三个定义之间的相关性在大多数年龄范围内都是正相关的,尤其是在两个细胞内面板之间,以及CD4+CD25hivsCD4+CD25hiCD127low。Treg和Breg频率在7年和3年后趋于下降,分别。Treg的成熟状态随着年龄的增长而增加,从7岁起,幼稚Treg下降,记忆/效应Treg增加。记忆障碍从3岁开始逐渐增加。总之,根据所使用的免疫表型定义,Treg频率的数量跨越很宽的范围,尽管它们之间存在良好的相关性.Breg的数量下降和随着年龄的增长而成熟的过程比Treg更早。