T-cell brain infiltration and immature antigen-presenting cells in transgenic models of Alzheimer's disease-like cerebral amyloidosis.

Cerebral beta-amyloidosis, one of the pathological hallmarks of Alzheimer's disease (AD), elicits a well-characterised, microglia-mediated local innate immune response. In contrast, it is not clear whether cells of the adaptive immune system, in particular T-cells, react to cerebral amyloidosis in AD. Even though parenchymal T-cells have been described in post-mortem brains of AD patients, it is not known whether infiltrating T-cells are specifically recruited to the extracellular deposits of beta-amyloid, and whether they are locally activated into proliferating, effector cells upon interaction with antigen-presenting cells (APCs). To address these issues we have analysed by confocal microscopy and flow-cytometry the localisation and activation status of both T-cells and APCs in transgenic (tg) mice models of AD-like cerebral amyloidosis. Increased numbers of infiltrating T-cells were found in amyloid-burdened brain regions of tg mice, with concomitant up-regulation of endothelial adhesion molecules ICAM-1 and VCAM-1, compared to non-tg littermates. The infiltrating T-cells in tg brains did not co-localise with amyloid plaques, produced less interferon-gamma than those in controls and did not proliferate locally. Bona-fide dendritic cells were virtually absent from the brain parenchyma of both non-tg and tg mice, and APCs from tg brains showed an immature phenotype, with accumulation of MHC-II in intracellular compartments. These results indicate that cerebral amyloidosis promotes T-cell infiltration but interferes with local antigen presentation and T-cell activation. The inability of the brain immune surveillance to orchestrate a protective immune response to amyloid-beta peptide might contribute to the accumulation of amyloid in the progression of the disease.

Amplitude-encoded calcium oscillations in fish cells.

The reaction of intracellular Ca(2+) to different agonist stimuli in primary hepatocytes from rainbow trout (Oncorhynchus mykiss) as well as the permanent fish cell line RTL-W1 was investigated systematically. In addition to "classical" agonists such as phenylephrine and ATP, model environmental toxicants like 4-nitrophenol and 3,4-dichloroaniline were used to elucidate possible interactions between toxic effects and Ca(2+) signaling. We report Ca(2+) oscillations in response to several stimuli in RTL-W1 cells and to a lesser extent in primary hepatocytes. Moreover, these Ca(2+) oscillations are amplitude-encoded in contrast to their mammalian counterpart. Bioinformatics and computational analysis were employed to identify key players of Ca(2+) signaling in fish and to determine likely causes for the experimentally observed differences between the Ca(2+) dynamics in fish cells compared to those in mammalian liver cells.