An effective form of innate immunity involves naive T-cells initiating a specific response to a pathogen (1). Mononuclear phagocytes producing IL-12 upon stimulation by microbial products or direct infection are central to this response. IL-12 induces the production of IFN-γ by T-cells and NK-cells, and naive T-cells develop preferentially into T-helper-1 (Th1) lymphocytes (1).

Neonates are deficient in the production of IFN-γ, a potent macrophage-activating agent in vivo (2). Memory T cell deficiency in neonatal blood compared to adult blood (12.3 %versus 55.2 % memory cells and 87.6% vs 44.8% naive cells in cord and adult blood, respectively) has been suggested to be responsible for the neonatal deficiency of IFN-γ production (3). In a recent study, Joyner et al. proposed that decreased production of IL-12 may also be linked to IFN-γ deficiency in newborns (4). They studied group B streptococcus (GBS)-stimulated mRNA accumulation and protein secretion of both IFN-γ and IL-12 in mononuclear cells from cord and adult blood. By using reverse transcriptase polymerase chain reaction and quantitative densitometry assays, the authors compared kinetics of GBS-stimulated accumulation of IFN-γ mRNA and IL-12 mRNA (both p40 and p35 subunits) in cord and adult cells. After 12-18 h of incubation, they detected significantly decreased mRNA accumulation for both IFN- and IL-12 in cord cells compared to adults. The concentration of IFN-γ and IL-12 in suspensions of GBS-induced cord mononuclear cells was also significantly lower than in adults at 12 and 18 h. The data presented in this paper suggest that IFN-γ deficiency in neonates may be attributed, in addition to lymphocyte immaturity, to decreased production of IL-12 by cord mononuclear phagocytes.

IL-2, another potent IFN-γ-inducing cytokine, is produced in nearly equal amounts by both memory and naive T cells from neonatal and adult blood (2). Therefore, the striking discrepancy between neonatal and adult IFN-γ production does not seem to be related to deficient IL-2 induction of IFN-γ. However, IL-2 receptor-mediated signaling and IFN-γ release by IL-2-induced neonatal T cells have not been studied.

The main conclusion that can be drawn from the work by Joyner et al. is that strategies to enhance neonatal host defense against intracellular pathogens may include administration of IL-12. Much remains to be answered, however, about cellular responsiveness of neonatal T-cells and monocytes/macrophages to cytokines critical to Th1 differentiation. For example, neonatal macrophages cannot be fully activated by IFN-γ, which may represent developmental immaturity (5).