The ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year: a cohort study.
The ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year: a cohort study.
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DOI：
10.1038/cti.2015.2
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发表时间：
2015-03
影响因子：
5.8
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由于对出生后第一年内幼稚和调节性CD 4 + T细胞亚群的纵向发育和早期个体发育的了解有限，我们试图评估出生后第一年内幼稚（胸腺和中央）和调节性（静息和活化）CD 4 + T细胞群比例的变化。从130名婴儿的人群来源样本中采集出生时、6个月和12个月大时的血液样本并进行分析。通过流式细胞术确定初始和调节性CD 4 + T细胞群的比例，并对胸腺和中央初始群进行分选，并通过T细胞受体切除环DNA（TREC）的相对表达确认其表型。出生时，大多数（94%）的CD 4 + T细胞是幼稚的（CD 45 RA+），其中约80%具有胸腺幼稚表型（CD 31+和高TREC），其余的已经是中央幼稚细胞（CD 31 −和低TREC）。在出生后的第一年，幼稚的CD 4 + T细胞保留了整体胸腺表型，但稳步下降。从出生到6月龄，静息的幼稚调节性T细胞（rTreg; CD 4 + CD 45 RA + FoxP 3+）和活化的Treg（aTreg，CD 4 + CD 45 RA − FoxP 3 high）的比例显著增加。在出生后的第一年，胸腺与中央幼稚CD 4 + T细胞的比例在男性中较低，表明免疫发育中的早期性二型性。这项纵向研究定义了出生后第一年内CD 4 + T细胞群的比例，从而更好地了解正常的免疫发育。
As there is limited knowledge regarding the longitudinal development and early ontogeny of naïve and regulatory CD4+ T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naïve (thymic and central) and regulatory (resting and activated) CD4+ T-cell populations during the first postnatal year. Blood samples were collected and analyzed at birth, 6 and 12 months of age from a population-derived sample of 130 infants. The proportion of naïve and regulatory CD4+ T-cell populations was determined by flow cytometry, and the thymic and central naïve populations were sorted and their phenotype confirmed by relative expression of T cell-receptor excision circle DNA (TREC). At birth, the majority (94%) of CD4+ T cells were naïve (CD45RA+), and of these, ~80% had a thymic naïve phenotype (CD31+ and high TREC), with the remainder already central naïve cells (CD31− and low TREC). During the first year of life, the naïve CD4+ T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naïve T regulatory cells (rTreg; CD4+CD45RA+FoxP3+) and activated Treg (aTreg, CD4+CD45RA−FoxP3high) increased markedly. The ratio of thymic to central naïve CD4+ T cells was lower in males throughout the first postnatal year indicating early sexual dimorphism in immune development. This longitudinal study defines proportions of CD4+ T-cell populations during the first year of postnatal life that provide a better understanding of normal immune development.