Rotavirus activates dendritic cells derived from umbilical cord blood monocytes.

Rotavirus is the most common cause of acute infectious diarrhea in human neonates and infants. However, the studies aimed at dissecting the anti-virus immune response have been mainly performed in adults. Dendritic cells (DCs) play a crucial role in innate and acquired immune responses. Therefore, it is very important to determine the response of neonatal and infant DCs to rotavirus and to compare it to the response of adult DCs. Thus, we determined the response of monocyte-derived DCs from umbilical cord blood (UCB) and adult peripheral blood (PB) to rotavirus in vitro. It was found that the rotavirus and its genome, composed of segmented doubled stranded RNA (dsRNA), induced the activation of neonatal DCs, as these cells up-regulated the levels of CD40, CD86, MHC II, TLR-3 and TLR-4, the production of cytokines IL-6, IL-12/23p40, IL-10, TGF-ß (but not of IL-12p70), and the message for TNF-α and IFN-ß. This activation enabled the neonatal DCs to induce a strong proliferation of allogeneic CD4+ T cells and the production of IFN-γ. Moreover, neonatal DCs could be infected by rotavirus and sustain its replication. Neonatal DCs had a similar response as adult DCs towards rotavirus and its genome. However, adult DCs had a biased pro-inflammatory response compared to neonatal DCs, which showed a biased regulatory profile, as they produced higher levels of IL-10 and TGF-ß, and were less efficient in inducing a Th1 type response. So it can be concluded that rotavirus and its genome can induce the activation of neonatal DCs in spite of their tolerogenic bias.

CD43 signals prepare human T cells to receive cytokine differentiation signals.

T cells are increasingly used for passive immunotherapy and bone marrow transplantation. Proper ex-vivo management of the cells is important for the desired therapeutic effects. For differentiation into effector cells of the Th1 and Th2 phenotypes, T-cells require signals from IFNγ and IL-4, respectively. Naïve cells have an extremely low expression of the specific receptors that recognize these cytokines, indicating that in order to differentiate, cells need to perceive other signals that will enable them to sense the cytokine milieu. CD43 has been proposed as one of the molecules that make the initial contacts with antigen presenting cells. We report here that in cord blood, adult naïve and total human T cells, CD43 signals induced the expression of both IFNγ and IL-4 receptors, mediate their capping, increased their signaling and augmented differentiation mediated by these receptors. CD43 signals also stimulated the expression of IFNγ and in neonatal cells that of IL-4 as well. These data demonstrate an important role for CD43 signals in T-cell preparedness for differentiation into effector cells.