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

As there is limited knowledge regarding the longitudinal development and early ontogeny of naive and regulatory CD4+ T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naive (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 naive and regulatory CD4(+) T-cell populations was determined by flow cytometry, and the thymic and central naive 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 naive (CD45RA(+)), and of these, similar to 80% had a thymic naive phenotype (CD31(+) and high TREC), with the remainder already central naive cells (CD31(-) and low TREC). During the first year of life, the naive CD4(+) T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naive T regulatory cells (rTreg; CD4(+) CD45RA(+) FoxP3(+)) and activated Treg (aTreg, CD4(+) CD45RA-FoxP3(high)) increased markedly. The ratio of thymic to central naive 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.