CD4+ T cell activation during the newborn period: Barriers against and pathways toward Th1 immunity

During the period of transition from intrauterine to extrauterine life, the neonatal immune system must learn to rapidly identify pathogens while balancing pro-inflammatory, antimicrobial responses with immune regulation that allows for resolution of inflammation and limits responses to commensal organisms and benign environmental antigens. However, the naive immune system of neonates is presented with several barriers that limit robust proinflammatory immune responses. Specifically, epigenetic modifications to neonatal naive CD4+ T cells, heightened neonatal regulatory T cell frequency and function, and limitations in the co-stimulatory potential of neonatal antigen presenting cells restrict development of CD4+ T cells with a T-helper 1 type functional profile. This restriction likely contributes to the increased risk of severe infection observed during early life. New research, however, suggests that neonates are capable of utilizing unique compensatory mechanisms to circumvent these restrictions and generate T-helper 1 type immunity under some circumstances. Understanding how to manipulate the immune responses of young infants to optimize development of T-helper 1 type immunity is key to the development of immune-based treatments and prevention strategies for severe infections in this vulnerable population.