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de Groot, Ronald

de Jonge, Marien I.

Eleveld, Marc J.

Ferwerda, Gerben

Jans, Jop

Raeven, Elisabeth A.M.

Simonetti, Elles R.

Unger, Wendy W.

English

Jans, J.

Unger, Wendy W.J.

Simonetti, E.R.

Eleveld, M.J.

de Groot, R.

Jonge, M.I. de

Ferwerda, G.

Radboud Repository

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 α/β 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-β-mediated inhibition of CD4+ T-cell proliferation, phosphorylation of retinoblastoma protein and cytokine production in human newborns compared to adults. In addition, both naïve and total newborn CD4+ T-cells are unable to induce the cell-cycle inhibitor p21 upon exposure to IFN-β in contrast to adults. The distinct IFN-β-signaling in newborns provides novel insights into T cell functionality and regulation of T cell-dependent inflammation during early life immune responses.</p

EUR Research Repository