Significant augmentation of regulatory T cell numbers occurs during the early neonatal period

Regulatory T cells (Tregs ) control immune responses by suppressing various inflammatory cells. Tregs in newborn babies may play an important role in preventing excessive immune responses during their environmental change. We examined the number and phenotype of Tregs during the neonatal period in 49 newborn babies. Tregs were characterized by flow cytometry using cord blood (CB) and peripheral blood (PB) from the early (7-8 days after birth) and late (2-4 weeks after birth) neonatal periods. CD4+ forkhead box protein 3 (FoxP3+ ) T cells were classified into resting Tregs (CD45RA+ FoxP3low ), activated Tregs (CD45RA- FoxP3high ) and newly activated T cells (CD45RA- FoxP3low ). Compared with CB and PB during the late neonatal period, the percentage of Tregs and all Treg subpopulations in the CD4+ lymphocyte population were increased significantly during the early neonatal period. Furthermore, the proportion and absolute number of activated Tregs were increased markedly compared with other Treg subpopulations, such as resting Tregs and newly activated T cells (non-Tregs ), in the early neonatal period. Increased Tregs concomitantly expressed the suppressive molecule cytotoxic T lymphocyte antigen-4 (CTLA-4). The up-regulated expression of chemokine receptor 4 (CCR4) and down-regulated expression of CCR7 were also observed in expanded Tregs . When cord blood cells were cultured in vitro with CD3 monoclonal antibodies (mAb) for 5 days, CD4+ CD45RA- FoxP3high cells were increased significantly during the culture. Thus, the presence of increased activated Tregs in early neonates may play an important role in immunological regulation by suppressing excessive T cell activation caused by the immediate exposure to ubiquitous antigens after birth.