Lack Of Cell Cycle Inhibitor P21 And Low Cd4(+) T Cell Suppression In Newborns After Exposure To Ifn-Beta

Type I IFNs, such as interferon alpha and interferon beta, are key regulators of the adaptive immune response during infectious diseases. Type I IFNs are induced upon infection, bind interferon alpha/beta receptors on T-cells and activate intracellular pathways. The activating and inhibitory consequences of type I IFN-signaling are determined by cell type and cellular environment. The neonatal immune system is associated with increased vulnerability to infectious diseases which could partly be explained by an immature CD4(+) T-cell compartment. Here, we show low IFN-beta-mediated inhibition of CD4(+) T-cell proliferation, phosphorylation of retinoblastoma protein and cytokine production in human newborns compared to adults. In addition, both naive and total newborn CD4(+) T-cells are unable to induce the cell-cycle inhibitor p21 upon exposure to IFN-beta in contrast to adults. The distinct IFN-beta-signaling in newborns provides novel insights into T cell functionality and regulation of T cell-dependent inflammation during early life immune responses.