The effect of dexamethasone on polyclonal T cell activation and redirected target cell lysis as induced by a CD19/CD3-bispecific single-chain antibody construct

BiTE molecules comprise a new class of bispecific single-chain antibodies redirecting previously unstimulated CD8+ and CD4+ T cells for the elimination of target cells. One example is MT103 (MEDI-538; bscCD19xCD3), a CD19-specific BiTE that can induce lysis of normal and malignant B cells at low picomolar concentrations, which is accompanied by T cell activation. Here, we explored in cell culture the impact of the glucocorticoid derivative dexamethasone on various activation parameters of human T cells in response to MT103. In case cytokine-related side effects should occur with BiTE molecules and other T cell-based approaches during cancer therapy it is important to understand whether glucocorticoids do interfere with the cytotoxic potential of T cells. We found that MT103 induced in the presence of target cells secretion by peripheral T cells of interleukin (IL)-2, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-6, IL-10 and IL-4 into the cell culture medium. Production of all studied cytokines was effectively reduced by dexamethasone at a concentration between 1 and 3x10(-7) M. In contrast, upregulation of activation markers CD69, CD25, CD2 and LFA-1 on both CD4+ and CD8+ T cells, and T cell proliferation were barely affected by the steroid hormone analogue. Most importantly, dexamethasone did not detectably inhibit the cytotoxic activity of MT103-activated T cells against a human B lymphoma line as investigated with lymphocytes from 12 human donors. Glucocorticoids thus qualify as a potential co-medication for therapeutic BiTE molecules and other cytotoxic T cell therapies for treatment of cancer.     

Large beech (<Emphasis Type="Italic">Fagus sylvatica</Emphasis>) trees as ‘lifeboats’ for lichen diversity in central European forests

The forest management practices used in central Europe in the last several centuries have led to loss of lichen diversity that may be largely attributed to a loss of substrate variability and quantity. In an attempt to obtain information enabling us to mitigate this process, we surveyed affinity of lichen species to the substrates they currently occupy in six forest areas in the Czech Republic, located between 200 and 1000 m a.s.l. Tree bases and stems represented the most important substrate for lichen species, and especially so for threatened (i.e. red-listed) species. Lichen species richness per individual tree generally increased with stem diameter, especially for beech. Stems and tree bases of large-diameter beeches provide habitats that have enabled the survival of a crucial component of the red-listed lichen species in central Europe, far outweighing other tree species. The deciduous tree species that are commonly considered as favourable for lichen diversity (e.g. maples, ash, elms) were inhabited by only a few other lichen species additional to those associated with beech. This may be due to the low frequency of these tree species in most managed forests, and also some forest reserves, at the present time. Similarly, low incidence of dead wood in managed forests has likely limited its contribution to the lichen diversity, despite the high potential for lichen diversity associated with such substrates. It is thus apparent that bark of large-diameter live beech trees comprises a keystone habitat element in the provision of lichen diversity in central European forests.     

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Plant Systematics and Evolution -     

Eine einfache Apparatur für quantitative Mikroinjektion nebst Bemerkungen über plasmatische Injektion

Zusammenfassung Es wird eine Mikroinjektionseinrichtung beschrieben, welche an Stelle der üblichen Recordspritze eine elastische Dose als wesentlichen Bestandteil enthält, deren Volumen mittels Mikrometerschraube verändert wird. Zwei einfache Arbeitsvorteile erleichtern die reproduzierbare Abgabe (oder Aufnahme) meßbarer Flüssigkeitsmengen: es sind dies die Anbringung eines Quecksilbertropfens knapp innerhalb der Pipettenmündung und die Aufnahme von Paraffinöl in die Pipettenspitze vor Ansaugen der Injektionslösung. Die bewegten Mengen werden durch Vermessen des Volumens bestimmt, welches sie in der Pipettenspitze einnehmen. Die Schwierigkeiten, welche quantitativer Injektion von Seiten der Apparatur entgegenstehen, lassen sich in der angegebenen Art überwinden.Einige Beobachtungen über Plasmaquellung und Mischbarkeit des Plasmas mit Wasser, die bei Mikroinjektion eine Rolle spielen, werden kurz besprochen.     

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