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

Regulatory T cells (T_regs ) control immune responses by suppressing various inflammatory cells. T_regs in newborn babies may play an important role in preventing excessive immune responses during their environmental change. We examined the number and phenotype of T_regs during the neonatal period in 49 newborn babies. T_regs 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 T_regs (CD45RA⁺ FoxP3^low ), activated T_regs (CD45RA^- FoxP3^high ) and newly activated T cells (CD45RA^- FoxP3^low ). Compared with CB and PB during the late neonatal period, the percentage of T_regs and all T_reg subpopulations in the CD4⁺ lymphocyte population were increased significantly during the early neonatal period. Furthermore, the proportion and absolute number of activated T_regs were increased markedly compared with other T_reg subpopulations, such as resting T_regs and newly activated T cells (non-T_regs ), in the early neonatal period. Increased T_regs 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 T_regs . When cord blood cells were cultured in vitro with CD3 monoclonal antibodies (mAb) for 5 days, CD4⁺ CD45RA^- FoxP3^high cells were increased significantly during the culture. Thus, the presence of increased activated T_regs 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.