Interleukin 2 pathway is autonomously activated in human T11+3-4-6-8- thymocytes

Mitogenic membrane ligands have been shown to activate interleukin 2 (IL2) production only in mature T cells, IL2 constitutive secretion having not yet been demonstrated. Here we have isolated a population of T11+3-4-6-8- human thymocytes and CD7+/T11-3-4-6-8- prothymocytes which produce and consume IL2 upon phytohemagglutinin triggering. Interestingly, their proliferation in the absence of any exogenous stimulating agent was related to an autonomous use of the IL2 system (IL2 secretion and binding to its specific receptor, whose constitutive, functional expression in human early thymocytes was recently shown). The internal activation of this system before T cell receptor acquisition stresses the relevance of the understanding of the alternative activation pathway(s) in T cell development. These findings, together with the demonstration of IL2-promoted differentiation of human early thymocytes into mature T cells, suggest that IL2 may also be a growth and differentiation factor acting specifically early in T cell development.     

The DC-SIGN-related lectin LSECtin mediates antigen capture and pathogen binding by human myeloid cells

Liver and lymph node sinusoidal endothelial cell C-type lectin (LSECtin [CLEC4G]) is a C-type lectin encoded within the liver/lymph node-specific intercellular adhesion molecule-3-grabbing nonintegrin (L-SIGN)/dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN)/CD23 gene cluster. LSECtin expression has been previously described as restricted to sinusoidal endothelial cells of the liver and lymph node. We now report LSECtin expression in human peripheral blood and thymic dendritic cells isolated ex vivo. LSECtin is also detected in monocyte-derived macrophages and dendritic cells at the RNA and protein level. In vitro, interleukin-4 (IL-4) induces the expression of 3 LSECtin alternatively spliced isoforms, including a potentially soluble form (Delta 2 isoform) and a shorter version of the prototypic molecule (Delta3/4 isoform). LSECtin functions as a pathogen receptor, because its expression confers Ebola virus-binding capacity to leukemic cells. Sugar-binding studies indicate that LSECtin specifically recognizes N-acetyl-glucosamine, whereas no LSECtin binding to Mannan- or N-acetyl-galactosamine-containing matrices are observed. Antibody or ligand-mediated engagement triggers a rapid internalization of LSECtin,which is dependent on tyrosine and diglutamic-containing motifs within the cytoplasmic tail. Therefore, LSECtin is a pathogen-associated molecular pattern receptor in human myeloid cells. In addition, our results suggest that LSECtin participates in antigen uptake and internalization, and might be a suitable target molecule in vaccination strategies.     

Separation of heteroaromatic amines in food products

In recent years, many studies have dealt with the role of certain heteroaromatic amines (HAs) as mutagenic compounds, and their occurrence in foodstuffs. Here we examine the determination of HAs, focusing on the analytical strategies for their extraction and preconcentration from several matrices. We summarise the properties of heteroaromatic amines and the main drawbacks involved in their analysis, and then concentrate on the separation procedures, sorbents and solvents used in the sample treatment. We discuss the requirements of the analytical techniques and the strategies most frequently followed to achieve accurate results.