Dendritic cells constitutively secrete a population of small (50–90 nm diameter) Ag-presenting vesicles called exosomes. When sensitized with tumor antigenic peptides, dendritic cells produce exosomes, which stimulate anti-tumor immune responses and the rejection of established tumors in mice. Using a systematic proteomic approach, we establish the first extensive protein map of a particular exosome population; 21 new exosomal proteins were thus identified. Most proteins present in exosomes are related to endocytic compartments. New exosomal residents include cytosolic proteins most likely involved in exosome biogenesis and function, mainly cytoskeleton-related (cofilin, profilin I, and elongation factor 1α) and intracellular membrane transport and signaling factors (such as several annexins, rab 7 and 11, rap1B, and syntenin). Importantly, we also identified a novel category of exosomal proteins related to apoptosis: thioredoxin peroxidase II, Alix, 14-3-3, and galectin-3. These findings led us to analyze possible structural relationships between exosomes and microvesicles released by apoptotic cells. We show that although they both represent secreted populations of membrane vesicles relevant to immune responses, exosomes and apoptotic vesicles are biochemically and morphologically distinct. Therefore, in addition to cytokines, dendritic cells produce a specific population of membrane vesicles, exosomes, with unique molecular composition and strong immunostimulating properties.

Adeno-associated viruses (AAVs) are small, nonenveloped single-stranded DNA viruses that require helper viruses to facilitate efficient replication. Despite the presence of humoral responses to the wild-type AAV in humans, AAV remains one of the most promising candidates for therapeutic gene transfer to treat many genetic and acquired diseases. Characterization of the IgG subclass responses to AAV and study of the prevalence of both IgG and neutralizing factors to AAV types 1, 2, 5, 6, 8, and 9 in the human population are of importance for the development of new strategies to overcome these immune responses. Natural exposure to AAV types 1, 2, 5, 6, 8, and 9 can result in the production of antibodies from all four IgG subclasses, with a predominant IgG1 response and low IgG2, IgG3, and IgG4 responses. Prevalences of anti-AAV1 and -AAV2 total IgG determined by enzyme-linked immunosorbent assay were higher (67 and 72%) than those of anti-AAV5 (40%), anti-AAV6 (46%), anti-AAV8 (38%), and anti-AAV9 (47%). Furthermore, data showed that cross-reactions are important. The two highest neutralizing factor seroprevalences were observed for AAV2 (59%) and AAV1 (50.5%) and the lowest were observed for AAV8 (19%) and AAV5 (3.2%). Vectors based on AAV5, AAV8, and AAV9 may have an advantage for gene therapy in humans. Furthermore, among individuals seropositive for AAV5, AAV8, and AAV9, about 70-100% present low titers. Better characterization of the preexisting humoral responses to the AAV capsid and cross-reactivity will allow development of new strategies to circumvent AAV acquired immune responses.

Dendritic cells (DCs) secrete vesicles of endosomal origin, called exosomes, that bear major histocompatibility complex (MHC) and T cell costimulatory molecules. Here, we found that injection of antigen- or peptide-bearing exosomes induced antigen-specific naïve CD4+ T cell activation in vivo. In vitro, exosomes did not induce antigen-dependent T cell stimulation unless mature CD8alpha- DCs were also present in the cultures. These mature DCs could be MHC class II-negative, but had to bear CD80 and CD86. Therefore, in addition to carrying antigen, exosomes promote the exchange of functional peptide-MHC complexes between DCs. Such a mechanism may increase the number of DCs bearing a particular peptide, thus amplifying the initiation of primary adaptive immune responses.

Aims. This catalogue is aimed at presenting a compilation of all known AGN in a compact and convenient form and we hope that it will be useful to all workers in this field. Methods. Like the eleventh edition, it includes position and redshift as well as photometry (U, B, V) and 6 cm flux densities when available. We now give 20 cm rather than 11 cm flux densities.Results. The present version contains 85 221 quasars, 1122 BL Lac objects and 21 737 active galaxies (including 9628 Seyfert 1s), almost doubling the number listed in the 11th edition. We also give a list of all known lensed and double quasars.

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Abstract.We have compiled a list of 83 objects classified as Narrow-Line Seyfert 1 galaxies (NLS1s) or known to have a broad Balmer component narrower than 2 000 km s −1 . Of these, 19 turned out to have been spectroscopically misidentified in previous studies; only 64 of the selected objects are genuine NLS1s. We have spectroscopically observed 59 of them and tried to characterize their Narrow and Broad-Line Regions (NLR and BLR) by fitting the emission-lines with Gaussian and/or Lorentzian profiles. In most cases, the broad Balmer components are well fitted by a single Lorentzian profile, confirming previous claims that Lorentzian rather than Gaussian profiles are better suited to reproduce the shape of the NLS1s broad emission lines. This has consequences concerning their FWHMs and line ratios: when the broad Balmer components are fitted with a Lorentzian, most narrow line regions have line ratios typical of Seyfert 2s while, when a Gaussian profile is used for fitting the broad Balmer components, the line ratios are widely scattered in the usual diagnostic diagrams (Veilleux & Osterbrock 1987); moreover, the FWHM of the best fitting Lorentzian is systematically smaller than the FWHM of the Gaussian. We find that, in general, the [O III] lines have a relatively narrow Gaussian profile (∼200-500 km s −1 FWHM) with often, in addition, a second broad (∼500-1 800 km s −1 FWHM), blueshifted Gaussian component. We do not confirm that the [O III] lines are weak in NLS1s. As previously suggested, there is a continuous transition of all properties between NLS1s and classical Broad-Line Seyfert 1 Galaxies (BLS1s) and the limit of 2000 km s −1 used to separate the two species is arbitrary; R4570, the ratio of the Fe II to the Hβ fluxes, could be a physically more meaningful parameter to distinguish them.

Abstract. Most Seyfert 1 galaxies show strong Fe II lines in their spectrum having the velocity and width of the broad emission lines. To remove the Fe II contribution in these objects, an accurate template is necessary. We used very high signal-to-noise, medium resolution archive optical spectra of I Zw 1 to build such a template. I Zw 1 is a bright narrow-line Seyfert 1 galaxy. As such it is well suited for a detailed analysis of its emission line spectrum. Furthermore it is known to have a very peculiar spectrum with, in addition to the usual broad and narrow line regions, two emission regions emitting broad and blue shifted [O III] lines making it a peculiarly interesting object. While analysing the spectra, we found that the narrow-line region is, unlike the NLR of most Seyfert 1 galaxies, a very low excitation region dominated by both permitted and forbidden Fe II lines. It is very similar to the emission spectrum of a blob in η Carinae which is a low temperature (T e ∼ 6500 K), relatively high density (N e = 10 6 cm −3 ) cloud. The Fe II lines in this cloud are mainly due to pumping via the stellar continuum radiation field (Verner et al. 2002). We did not succeed in modelling the spectrum of the broad-line region, and we suggest that a non radiative heating mechanism increases the temperature in the excited H I region, thus providing the necessary additional excitation of the Fe II lines. For the low-excitation narrow-line region, we are able to apply boundaries to the physical conditions accounting for the forbidden and permitted Fe II lines (10 6 < N e < 10 7 cm −3 ; 10 −6 < U < 10 −5 ).

Aims. This catalogue is aimed at presenting a compilation of all known AGN in a compact and convenient form, and we hope that it will be useful to all workers in this field. Methods. Like the twelfth edition, it includes position and redshift, as well as photometry (U, B, V) and 6 cm and 20 cm flux densities, when available.Results. The present version contains 133 336 quasars, 1 374 BL Lac objects, and 34 231 active galaxies (including 16 517 Seyfert 1s), almost doubling the number listed in the 12th edition. We also give a list of all known lensed and double quasars.