Enhanced effector and memory CTL responses generated by incorporation of receptor activator of NF-kappa B(RANK)/RANK ligand costimulatory molecules into dendritic cell immunogens expressing a human tumor-specific antigen

The outcome of dendritic cell (DC) presentation of Ag to T cells via the TCR/MHC synapse is determined by second signaling through CD80/86 and, importantly, by ligation of costimulatory ligands and receptors located at the DC and T cell surfaces. Downstream signaling triggered by costimulatory molecule ligation results in reciprocal DC and T cell activation and survival, which predisposes to enhanced T cell-mediated immune responses. In this study, we used adenoviral vectors to express a model tumor Ag (the E7 oncoprotein of human papillomavirus 16) with or without coexpression of receptor activator of NF-kappaB (RANK)/RANK ligand (RANKL) or CD40/CD40L costimulatory molecules, and used these transgenic DCs to immunize mice for the generation of E7-directed CD8(+) T cell responses. We show that coexpression of RANK/RANKL, but not CD40/CD40L, in E7-expressing DCs augmented E7-specific IFN-gamma-secreting effector and memory T cells and E7-specific CTLs. These responses were also augmented by coexpression of T cell costimulatory molecules (RANKL and CD40L) or DC costimulatory molecules (RANK and CD40) in the E7-expressing DC immunogens. Augmentation of CTL responses correlated with up-regulation of CD80 and CD86 expression in DCs transduced with costimulatory molecules, suggesting a mechanism for enhanced T cell activation/survival. These results have generic implications for improved tumor Ag-expressing DC vaccines, and specific implications for a DC-based vaccine approach for human papillomavirus 16-associated cervical carcinoma.

Transient evoked otoacoustic emissions in adults: a comparison between two test protocols

This study compares the performance of the Quickscreen and Default protocols of the ILO-96 Otodynamics Analyzer in recording transient evoked otoacoustic emissions (TEOAEs) from adults using clinical decision analysis. Data were collected from 25 males (mean age = 29.0 years, SD = 6.8) and 35 females (mean age = 28.1 years, SD = 9.6). The results showed that the mean signal-to-noise ratios obtained from the Quickscreen were significantly greater than those from the Default protocol at 1,2, and 4 kHz. The comparison of the performance of the two protocols, based on the results using receiver operating characteristics curves, revealed a higher performance of the Quickscreen than the Default protocol at 1 and 4 kHz but not at 2 kHz. In view of the enhanced performance of the Quickscreen over the Default protocol in general, the routine use of the Default protocol for testing adults in audiology clinics should be reconsidered.