Infants are particularly susceptible to intracellular pathogens due to impaired Th1 immune response. Inherent CD4 T cells defect and immaturity of APC contribute to Th1/Th2 imbalenced. IL-27,a member of the IL-12 family ,promotes the initial differentiation of naïve CD4 t cell into Th1 effectors.To investigate the role of IL-27 in neonatal context, Laure Ysebrant de Lendonck and her research team study the synthesis of IL-27 by LPS stimulated cord blood monocytes derivated dendritic cells (moDC) and the effect of IL-27 on cord blood naïve CD4 T cell. Expression of IL-27 p28 was selectively impaired in cord blood moDC compaired with adult conterpart. Addition of exogenous IFN-β restores IL-27p28 in cord blood moDC.
Laure Ysebrant de Lendonck and her research team analysed the effect of recombinant human (rh) IL-27 on activation and lymphokines secretion of cord blood mononuclear cells (CBMC) and peripheral blood mononuclear cells (PBMC). Proliferation (assessed by H3 thymidin incorporation), CD69 expression and production of IFN-γ of polyclonally-activated CBMC were dramatically increased in presence of rhIL-27. In contrast, we observed no effect on adult PBMC.
They then studied activation and lymphokines secretion of isolated naive CD4+ CD45RA+ and memory CD4+ CD45RO+ T lymphocytes from CBMC and PBMC. IL-27 activated naïve CD4+ CD45RA+ T cells from CBMC and PBMC but had no effect on memory CD4+CD45 RO+ T cells activation. In agreement with previous reports (2), we observed that polyclonaly-activated naive CD4+ CD45RA T cells from CBMC have a decreased capacity to produce IFN-g in comparison with their adult counterparts .Incubation with rhIL-27 restored the production of IFN-g to adult levels, induced the expression of the Th1 transcription factor T-bet and of IL-12RB2 by naive CD4+ CD45RA+ from CBMC. In contrast, IL-27 had no effect on the production of IFN-γ by CD4+ CD45RO+ T cells.
They conclude that IL-27 exerces direct and diffrentiel effects on CD4T cells and potentiate the production of IFN-γ by naïve cord blood CD4 t cells.