Newborns and young children rely on innate immunity to protect against infections until the adaptive immune system matures. Immunization helps facilitate protection, but multiple doses are needed to establish sufficient antibody levels and T-cell-facilitated immune memory. Deficient T-cell activation and function among neonates and young children are primarily present in the CD4+ compartment, whereas CD8+ T-cell function is at par with adults. CD4+ T cells in neonates and young children produce low levels of IFNγ, interleukin (IL)-2, IL-13, IL-5, and IL-17. This inherent deficiency in neonatal and young child CD4+ T-cell functionality has been linked to several mechanistic failures: (1) lower sensitivity to T-cell receptor stimulation, (2) increased apoptosis after proliferation, (3) unavailability of antigen for T-cell priming, and (4) inefficient stimulation by relatively immature antigen-presenting cells. In this review, we discuss evidence from infection and vaccination responses that shed light on the various checkpoints possibly involved in delayed maturation of CD4+ T-cell activation and function in newborns and young children.
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