Neonatal CD8+ T-cell differentiation is dependent on interleukin-12

Neonatal CD8+ T-cell activation is significantly impaired compared with that in adults. Recent studies have demonstrated that interleukin (IL)–12 is necessary as a third signal, in addition to antigen and co-stimulation, to authorize the differentiation of naive CD8+ T cells. We examined whether human neonatal CD8+ T cells, which possess an exclusively naive T-cell phenotype, required a third signal to authorize a productive T-cell response. IL-12 enhanced activated naive CD8+ T-cell survival, expansion, CD25 expression, and IL-2 production. Activated CD8+ T cells produced interferon-γ and intracellular granzyme B and were cytotoxic only in the presence of IL-12. Sustained IL-12 signaling for 72 hours was required for optimal interferon-γ production. IL-12, in concert with T cell receptor (TCR) stimulation, sustained late-stage (48–72 hours) intracellular phosphorylation and particularly total protein levels of the proximal TCR components, Lck, and CD3ξ. The requirement for a third signal for productive human neonatal CD8+ T-cell differentiation may have implications for neonatal vaccination strategies.