We have generated a panel of mAbs that identify three presumably novel human dendritic cell Ags: BDCA-2, BDCA-3, and BDCA-4. In blood, BDCA-2 and BDCA-4 are expressed on CD11c− CD123bright plasmacytoid dendritic cells, whereas BDCA-3 is expressed on small population of CD11c+ CD123− dendritic cells. All three Ags are not detectable on a third blood dendritic cell population, which is CD1c+ CD11cbright CD123dim, or on any other cells in blood. BDCA-4 is also expressed on monocyte-derived and CD34+ cell-derived dendritic cells. Expression of all three Ags dramatically changes once blood dendritic cells undergo in vitro maturation. BDCA-2 is completely down-regulated on plasmacytoid CD11c− CD123bright dendritic cells, expression of BDCA-3 is up-regulated on both plasmacytoid CD11c− CD123bright dendritic cells and CD1c+ CD11cbright CD123dim dendritic cells, and expression of BDCA-4 is up-regulated on CD1c+ CD11cbright CD123dim dendritic cells. BDCA-2 is rapidly internalized at 37°C after mAb labeling. The three presumably novel Ags serve as specific markers for the respective subpopulations of blood dendritic cells in fresh blood and will be of great value for their further analysis and to evaluate their therapeutic potential.

Acquiring resistance against transforming growth factor b (TGFb)-induced growth inhibition at early stages of carcinogenesis and shifting to TGFb's tumour-promoting functions at later stages is a pre-requisite for malignant tumour progression and metastasis. We have identified the transcription factor distal-less homeobox 2 (Dlx2) to exert critical functions during this switch. Dlx2 counteracts TGFb-induced cell-cycle arrest and apoptosis in mammary epithelial cells by at least two molecular mechanisms: Dlx2 acts as a direct transcriptional repressor of TGFb receptor II (TGFbRII) gene expression and reduces canonical, Smad-dependent TGFb signalling and expression of the cell-cycle inhibitor p21 CIP1 and increases expression of the mitogenic transcription factor c-Myc. On the other hand, Dlx2 directly induces the expression of the epidermal growth factor (EGF) family member betacellulin, which promotes cell survival by stimulating EGF receptor signalling. Finally, Dlx2 expression supports experimental tumour growth and metastasis of B16 melanoma cells and correlates with tumour malignancy in a variety of human cancer types. These results establish Dlx2 as one critical player in shifting TGFb from its tumour suppressive to its tumour-promoting functions.

The association of delayed skin reactions with allergen specific T-cell parameters in the blood points to an immunologically mediated mechanism leading to positive reactions in the APT.

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A genetic approach has been developed to study transcription by RNA polymerase III. A pair of Schizosaccharomyces pombe nonsense suppressor tRNA genes were arranged in tandem such that expression of the downstream (supS1) tRNA suppressor was dependent upon transcription initiated by the internal promoter of the upstream (sup9‐e) gene. Dominant mutant strains of Saccharomyces cerevisiae were isolated that suppress in trans the effect of an A block promoter mutation (A19) in the sup9‐e gene and restore supS1 suppressor activity. Fifteen mutant strains, eight of which were independently isolated, all have elevated steady‐state levels of sup9‐e A19 RNA consistent with an increase in gene transcription. Extracts of a strain carrying the dominant mutant gene, PCF1, show a general 6‐fold stimulation in transcription of mutant (A19) and wild‐type tRNA genes and increase 5S gene transcription 4‐fold compared with extracts from a wild‐type strain. A transcription factor exclusion assay was used to show that the PCF1 mutation affects two distinct stages in transcription: one prior to and one after stable complex formation; and that these effects are mediated by a component of the stable complex. Further evidence of an effect during complex assembly was obtained in a time‐course experiment that showed a shortened lag phase in the PCF1 extract. The results indicate that PCF1 is either a component of the stable complex or a positive regulator of its activity.