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Infection of γδT cell-deficient (TcRδ−/−) mice with the intracellular bacterium Listeria monocytogenes ( Lm) results in an exacerbated inflammatory response characterized by the accumulation of activated macrophages and necrotic liver lesions. Here we investigated whether changes in chemokine production by Lm-elicited macrophages contribute to this abnormal inflammatory response. In response to Lm infection, activated macrophages accumulate in the primary sites of infection in TcRδ−/− mice and express high amounts of mRNA encoding the chemokines CCL3 (MIP-1α), CCL4 (MIP-1β), CXCL2 (MIP-2) and CXCL10 (IP-10). In the infected tissues of TcRδ−/− the number of chemokine-synthesizing macrophages was higher than in wild-type (WT) mice, with the amount of MIP-1α and MIP-1β secreted by individual macrophages in the spleen of TcRδ−/− mice also being significantly higher than in WT mice. By contrast, protease activity and NO production in individual splenic macrophages of Lm-infected TcRδ−/− and WT mice were comparable. Pathogen-elicited macrophages in TcRδ−/− mice also expressed high levels of the CCL3 and CCL4 receptor, CCR5. In macrophage-γδT cell co-cultures, chemokine-producing macrophages were killed by cytotoxic Vγ1+ T cells in a Fas-FasL-dependent manner consistent with the high levels of chemokine-producing macrophages seen in infected TcRδ−/− mice being due to the absence of Vγ1+ T cells. Together these findings highlight the importance of γδT cells in regulating macrophage anti-microbial responses. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

MicroRNAs are naturally occurring small RNA species that regulate gene expression and are frequently abnormally expressed in cancers. However, the role of microRNAs in lymphoma is poorly understood. Therefore, we undertook a comprehensive study of microRNA expression in two of the most common lymphomas: diffuse large B-cell lymphoma (DLBCL) (n = 80) and follicular lymphoma (FCL) (n = 18) using microarrays containing probes for 464 human microRNAs. Unsupervised cluster analysis revealed distinct expression patterns between these two lymphomas and specific microRNA signatures (including members of the miR-17-92 cluster) were derived that correctly predicted lymphoma type in >95% of cases. Furthermore, we identified microRNAs in de novo DLBCL (n = 64) associated with germinal centre-like and non-germinal centre-like immunophenotypes, international prognostic index status and event-free survival in CHOP and rituximab (R)-CHOP treated patients. Despite the indolent nature of FCL a significant proportion of cases undergo high-grade transformation to more aggressive DLBCL. In order to see if transformation is associated with changes in microRNA expression we compared transformed DLBCL cases (n = 16) with de novo DLBCL, as well as FCL cases that underwent subsequent transformation (n = 7) with FCL cases that had not transformed at a median follow-up of 60 months (n = 11). Differential expression of 12 microRNAs correctly predicted >85% of transformed versus de novo DLBCL cases; six microRNAs (miR-223, 217, 222, 221 and let-7i and 7b) were found which could similarly predict or transformation in FCL (P < 0.05). These data suggest that microRNAs have potential as diagnostic and prognostic markers in these lymphomas and may be used to identify FCL patients at risk of high-grade transformation.