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

Abstract

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. A longitudinal study of blood samples from 130 infants in their first year reveals new insights into normal immune development. The investigation incorporated babies from the Barwon Infant Study and was led by Fiona Collier from University Hospital, Geelong, Australia. It showed that at birth, more than 90% of the infants' immune cells were naïve and thus able to respond to novel pathogens. During the first six months of life, the proportion of naïve cells steadily decreased while the number of non‐naïve or activated T cells increased, consistent with development of the immune system in the infectious extra‐uterine environment. Male babies had a lower proportion of non‐activated naïve T cells over the first 12 months of life compared with females, which could mark the earliest signs of gender‐specific differences in development of the immune system.