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.