The ontogeny of naïve and regulatory CD4+ T-cell subsets during the first postnatal year: a cohort study

摘要

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⁻FoxP3^high) 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.