Innate immunity

Impairment of dendritic cells and adaptive immunity by Ebola and Lassa viruses. Mahanty, S. et al. J. Immunol. 170, 2797–2901 (2003)

Ebola and Lassa viruses cause haemorrhagic fevers. Early infection seems to be associated with the release of pro-inflammatory mediators. But people who survive Lassa-virus infection show signs of immune suppression and delayed adaptive immune responses. The role of dendritic cells (DCs) in Ebola and Lassa virus infections is not known. The results of this study show that both viruses can infect and replicate in human monocyte-derived DCs. Infected DCs did not secrete several pro-inflammatory cytokines and co-stimulatory molecules were not upregulated. Furthermore, these DCs failed to induce T-cell proliferation in mixed-lymphocyte reaction assays. These results indicate that DCs do not become activated after virus infection, either because of active suppression of DCs or failure of DC maturation.

Signal transduction

Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapse. Ardouin, L. et al. Eur. J. Immunol. 33, 790–797 (2003)

T-cell receptor (TCR)-triggered rearrangement of the actin cytoskeleton is crucial for T-cell activation. It was suspected that Vav1, a guanine nucleotide exchange factor for the Rho-family GTPases, is involved in these processes as Rho-family proteins are important regulators of the actin cytoskeleton and Vav1-deficient T cells have defective TCR-signal transduction. As Vav1−/− TCR-transgenic mice lack mature T cells, CD4+CD8+ thymocytes from these mice were examined for cytoskeleton-dependent TCR-driven events. Although Vav1 was not required for the clustering of proteins at the immunological synapse, it was essential for 'inside-out' signals that lead to the activation of the integrin LFA1 and for the polarization of the microtubule-organizing centre towards the immunological synapse.

Dendritic cells

Compartmentalized production of CCL17 in vivo : strong inducibility in peripheral dendritic cells contrasts selective absence from the spleen. Alferink, J. et al. J. Exp. Med. 197, 585–599 (2003)

Several chemokines have been implicated in the attraction of T cells by dendritic cells (DCs), including CCL22 and CCL17, which bind to the chemokine receptor CCR4 on activated T cells. To clarify the role of CCL17, mice were created in which a green fluorescent protein reporter gene was inserted into the Ccl17 locus. The highest expression level of CCL17 was by mature myeloid DCs, including the Langerhan's cells of the skin and the DCs of the Peyer's-patch subepithelial dome. Exposure to Toll-like receptor ligands was found to upregulate the expression of CCL17 by these peripheral DCs. But, strikingly, splenic DCs never expressed CCL17, even after systemic microbial challenge.