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

Fiona M Collier; Mimi L K Tang; David Martino; Richard Saffery; John Carlin; Kim Jachno; Sarath Ranganathan; David Burgner; Katrina J Allen; Peter Vuillermin; Anne-Louise Ponsonby

doi:10.1038/cti.2015.2

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

Clin Transl Immunology. 2015 Mar 27;4(3):e34. doi: 10.1038/cti.2015.2. eCollection 2015 Mar.

Affiliations

¹ Child Health Research Unit and Barwon Biomedical Research, University Hospital, Barwon Health , Geelong, Victoria, Australia ; School of Medicine, Deakin University , Waurn Ponds, Victoria, Australia ; Murdoch Childrens Research Institute , Parkville, Victoria, Australia.
² Murdoch Childrens Research Institute , Parkville, Victoria, Australia ; The Royal Childrens Hospital , Parkville, Victoria, Australia ; The University of Melbourne , Parkville, Victoria, Australia.
³ Murdoch Childrens Research Institute , Parkville, Victoria, Australia ; The University of Melbourne , Parkville, Victoria, Australia.
⁴ Murdoch Childrens Research Institute , Parkville, Victoria, Australia.

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.