INTERLEUKIN 12 EXERTS A DIFFERENTIAL EFFECT ON THE MATURATION OF NEONATAL AND ADULT HUMAN CD45R0(-) CD4 T-CELLS

It is now recognized that IL-12 plays a predominant role in protective immunity against intracellular pathogens by promoting the development of T helper type 1 (Th1) responses. We here report the unexpected obs ervations that IL-12 exerts differential effects on the maturation of ''naive'' human CD4 T cells isolated from umbilical cord blood or from the blood of healthy adults. After priming in the presence of IL-12, naive cells of adult donors, defined as CD45RO(-) CD4(+) T cells, acqu ire a Th1 phenotype whereas neonatal cells develop into effector cells producing high levels of IL-4 in addition to IFN-gamma. This effect o f IL-12 on neonatal T cells is direct inasmuch as it is observed on hi ghly purified CD4 T cells, however, it is not inhibited by CDS T cells and natural killer cells. Unstimulated neonatal T cells which have be en preincubated with IL-12 before the priming behave like adult T cell s and acquire a Th1 phenotype after stimulation in the presence of IL- 12. Given that IL-4 is a potent antagonist of Th1 responses, the findi ng that IL-12 promotes the maturation of neonatal T cells into IL-4 pr oducers may explain the increased susceptibility of neonates to intrac ellular pathogens and should be taken into account for the development of vaccines to be used in the perinatal period.