Interleukin-27: A Modulator of Th1 Differentiation in human newborns (90.18)

Abstract

Abstract Objective: The initial description of IL-27 indicated that it plays a role in the early regulation of T helper type 1 (Th1) initiation, induces proliferation of naïve CD4 T cells and synergizes with IL-12 in IFN-γ production. Furthermore it has broad inhibitory effects on Th2 and Th17 subsets of T cells as well as the expansion of inducible regulatory T cells. As an IL-12-related cytokine IL-27 is frequently present at sites of inflammation that can promote both anti- and pro-inflammatory immune responses. To highlight the effects of IL-27 in the specific context of the neonatal immune response, we compared its role in CD4+ T cells in both human cord and adult blood. Methodology/Principal Findings: Umbilical cord blood samples were collected from healthy full-term infants born by cesarean sections. Leukocytes from adults were enriched from leucapheresis products. After density centrifugation, the mononuclear cell fraction (PBMC) was washed and cells were magnetically labelled for CD4+ T cells and enriched in a magnetic field, following stimulation with IL-27 for ascertainment of T cell response in vitro. Our data indicate that addition of IL-27 induced the production of IFNγ (n= 9-11; p=0,047) in neonatal CD4+ T cells, whereby IL-17 is decreased considerably. Furthermore we noticed enhanced phosphorylation of Stat-1 (n=6-9; p=0,008) in cord blood compared to adult blood. These data suggest that binding of IL-27 to its receptor initiates Th1 responses in naïve T cells of human newborns. Conclusions/Significance: Taken together, our results suggest that IL-27 compensate the restricted Th1 immune response in human newborns to a higher extend as compared to adult T cells.