The ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year: a cohort study
Collier, Fiona M., Tang, Mimi L. K., Martino, David, Saffery, Richard, Carlin, John, Jachno, Kim, Ranganathan, Sarath, Burgner, David, Allen, Katrina J., Vuillermin, Peter and Ponsonby, Anne-Louise 2015, The ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year: a cohort study, Clinical and translational immunology, vol. 4, no. 3, pp. 1-8, doi: 10.1038/cti.2015.2.
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.
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