Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells

Antigen-specific, CD8+, cytolytic T lymphocytes (CTLs) could potentially provide resistance to several infectious and malignant diseases. However, the cellular requirements for the generation of specific CTLs in human lymphocyte cultures are not well defined, and repetitive stimulation with antigen is often required. We find that strong CD8+ CTL responses to influenza virus can be generated from freshly isolated blood T cells, as long as dendritic cells are used as antigen presenting cells (APCs). Small numbers of dendritic cells (APC:T cell ratio of 1:50-1:100) induce these CTL responses from most donors in 7 d of culture, but monocytes are weak or inactive. Whereas both dendritic cells and monocytes are infected with influenza virus, the former serve as effective APCs for the induction of CD8+ T cells while the latter act as targets for the CTLs that are induced. The strong CD8+ response to influenza virus-infected dendritic cells is accompanied by extensive proliferation of the CD8+ T cells, but the response can develop in the apparent absence of CD4+ helpers or exogenous lymphokines. CD4+ influenza virus-specific CTLs can also be induced by dendritic cells, but the cultures initially must be depleted of CD8+ cells. These findings should make it possible to use dendritic cells to generate human, antigen-specific, CD8+ CTLs to other targets. The results illustrate the principle that efficient T cell-mediated responses develop in two stages: an afferent limb in which dendritic cells are specialized APCs and an efferent limb in which the primed T cells carry out an immune response to many types of presenting cells

Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells

Bhardwaj, N., Bender, A., Gonzalez, N., Bui, L.K., Garrett, M.C., and Steinman, R.M. Influenza virus-infected dendritic cells stimulate strong proliferative and cytolytic responses from human CD8+ T cells. J. Clin. Invest. 94: 797-807,1994https://digitalcommons.rockefeller.edu/historical-scientific-reports/1038/thumbnail.jp

Specific star formation rates to redshift 5 from the FORS Deep Field and the GOODS-S Field

We explore the build-up of stellar mass in galaxies over a wide redshift range 0.4 < z < 5.0 by studying the evolution of the specific star formation rate (SSFR), defined as the star formation rate per unit stellar mass, as a function of stellar mass and age. Our work is based on a combined sample of ~ 9000 galaxies from the FORS Deep Field and the GOODS-S field, providing high statistical accuracy and relative insensitivity against cosmic variance. As at lower redshifts, we find that lower-mass galaxies show higher SSFRs than higher mass galaxies, although highly obscured galaxies remain undetected in our sample. Furthermore, the highest mass galaxies contain the oldest stellar populations at all redshifts, in principle agreement with the existence of evolved, massive galaxies at 1 < z < 3. It is remarkable, however, that this trend continues to very high redshifts of z ~ 4. We also show that with increasing redshift the SSFR for massive galaxies increases by a factor of ~ 10, reaching the era of their formation at z ~ 2 and beyond. These findings can be interpreted as evidence for an early epoch of star formation in the most massive galaxies, and ongoing star-formation activity in lower mass galaxies.Comment: Accepted for publication in ApJL; 4 pages, 2 color figures, uses emulateapj.cl

The Munich Near-Infrared Cluster Survey (MUNICS) - IX. Galaxy Evolution to z ~ 2 From Optically Selected Catalogues

(Abridged) We present B, R, and I-band selected galaxy catalogues based on the Munich Near-Infrared Cluster Survey (MUNICS) which, together with the K-selected sample, serve as an important probe of galaxy evolution in the redshift range 0 < z < 2. Furthermore, used in comparison they are ideally suited to study selection effects. The construction of the B, R, and I-selected photometric catalogues, containing ~9000, ~9000, and ~6000 galaxies, respectively, is described in detail. The catalogues reach 50% completeness limits for point sources of B ~ 24.5mag, R ~ 23.5mag, and I ~ 22.5mag and cover an area of about 0.3 square degrees. Photometric redshifts are derived for all galaxies with an accuracy of dz/(1+z) ~ 0.057. We investigate the influence of selection band and environment on the specific star formation rate (SSFR). We find that K-band selection indeed comes close to selection in stellar mass, while B-band selection purely selects galaxies in star formation rate. We use a galaxy group catalogue constructed on the K-band selected MUNICS sample to study possible differences of the SSFR between the field and the group environment, finding a marginally lower average SSFR in groups as compared to the field, especially at lower redshifts. The field-galaxy luminosity function in the B and R band as derived from the R-selected sample evolves out to z ~ 2 in the sense that the characteristic luminosity increases but the number density decreases. This effect is smaller at longer rest-frame wavelengths and gets more pronounced at shorter wavelengths. Parametrising the redshift evolution of the Schechter parameters as M*(z) = M*(0) + a ln(1+z) and Phi*(z) = Phi*(0) (1+z)^b we find evolutionary parameters a ~ -2.1 and b ~ -2.5 for the B band, and a ~ -1.4 and b ~ -1.8 for the R band.Comment: 23 pages, 19 figures; accepted for publication in MNRAS; version with high-resolution figures will be made available at http://www.usm.uni-muenchen.de/people/feulner/munics9/preprint_munics9.pd

Bodengestützte GPS Wasserdampf-Tomographie

Die Signale des Global Positioning Systems (GPS) ermöglichen nicht nur die präzise Positionsbestimmung an jedem Ort der Erde, sondern enthalten auch Informationen über den Wasserdampfgehalt der Atmosphäre. Aus diesen Informationen kann mit Hilfe tomographischer Verfahren die dreidimensionale Wasserdampfverteilung in der Troposphäre rekonstruiert werden. Dabei ist es von besonderem Interesse, wie zuverlässig die Wasserdampfverteilung alleine aus den Daten bodengestützter GPS-Netzwerke, d. h. ohne die Einbeziehung von Low Earth Orbitern (LEOs) oder von Wettersatelliten, bestimmt werden kann. Zu diesem Zweck werden GPS-Daten für unterschiedliche GPS-Netzwerke simuliert und auf ihre Eignung für eine tomographische Rekonstruktion untersucht. Besonders der Zusammenhang zwischen der Anzahl der Satelliten, der Stationsdichte und der in der tomographischen Rekonstruktion erreichbaren Auflösung ist dabei von großer Bedeutung. Aus diesem Grund erfolgt zunächst eine geometrische Bewertung der GPS-Eingangsdaten. Die Rekonstruktion eines 3D-Feldes und die dabei auftretenden Abweichungen zwischen dem originalen und dem rekonstruierten Feld werden abschließend an einem Beispiel dargestellt.The signals of the global positioning system (GPS) can not only be used to obtain the precise position all over the world but carry also information about the water vapour distribution in the atmosphere. This 3D distribution can be reconstructed from the GPS data by means of tomographic techniques. Of special interest is the quality of the reconstructed 3D distribution using data from GPS ground stations alone, without regarding low earth orbiters (LEOs) and weather satellites. Therefore, GPS data have been simulated for different model networks. A subsequent data validation shows the correlation between the number of GPS satellites, the density of ground stations and the spatial resolution of the water vapour field which might be obtained from a tomographic reconstruction. Some selected data sets have been used to reconstruct a given 3D distribution and to analyse variations between the initial model field and the results obtained with different tomographic techniques

Final results of the DFG funded project “Development of a tomographic water vapour sounding system based on GNSS data”

Since 2008 a group of scientists of the Leipzig Institute of Meteorology (LIM) and the German Research Centre for Geosciences Potsdam (GFZ) develops a method to derive water vapour profiles out of continuously available GNSS data (Global Navigation Satellite System). The aim of this project - supported by the Deutsche Forschungsgemeinschaft (DFG) - was to develop a processing system with related scientific algorithms, which uses data of regional GNSS ground networks to derive 3D water vapour distributions above these stations. This systems use the line of sight water vapour information from each ground station to every GNSS satellite in view (slants) as basis of a 3D tomographic reconstruction. At this time these reconstructions are based on GNSS data of about 330 German or near Germany located groundstations. This leads to a horizontal resolution of the reconstructed 3D water vapour field up to 40km and a vertical resolution of about 0.5km from the upper part of troposphere down to the atmospheric boundary layer (1km height).Seit 2008 befasst sich eine Arbeitsgruppe von Wissenschaftlern am LIM und dem GFZ in Potsdam im Rahmen eines DFG-geförderten Projektes mit der Ableitung von dreidimensionalen Wasserdampfverteilungen in der Atmosphäre aus Beobachtungsdaten regionaler GNSS-Bodennetze (GlobaleNavigationsSatellitenSysteme). Die Wasserdampfverteilungen können aus der atmosphärischen Information entlang der Sichtlinien zwischen den Bodenstationen und den sichtbaren GNSS-Satelliten (sogenannte Slants) berechnet werden. Diese zahlreichen Sichtlinien ermöglichen eine tomographische Verarbeitung der Daten. Der entwickelte tomographische Algorithmus nutzt derzeit bis zu 330 deutsche und nahe Deutschland gelegene GNSS-Stationen, was eine horizontale Auflösung der resultierenden 3D-Felder von 40km und einer vertikalen Auflösung von 0,5km bis hinab zur atmosphärischen Grenzschicht (bis 1 km über dem Boden) ermöglich

WFPC2 Images of the Central Regions of Early-Type Galaxies - I. The Data

We present high resolution R-band images of the central regions of 67 early-type galaxies obtained with the Wide Field and Planetary Camera 2 (WFPC2) aboard the Hubble Space Telescope (HST). Our sample strikingly confirms the complex morphologies of the central regions of early-type galaxies. In particular, we detect dust in 43 percent of all galaxies, and evidence for embedded stellar disks in a remarkably large fraction of 51 percent. In 14 of those galaxies the disk-like structures are misaligned with the main galaxy, suggesting that they correspond to stellar bars in S0 galaxies. We analyze the luminosity profiles of the galaxies in our sample, and classify galaxies according to their central cusp slope. To a large extent we confirm the clear dichotomy found in previous HST surveys: bright, boxy ellipticals with shallow inner cusps (`core' galaxies) on one hand and faint, disky ellipticals with steep central cusps (`power-law' galaxies) on the other hand. The advantages and shortcomings of classification schemes utilizing the extrapolated central cusp slope are discussed, and it is shown that this cusp slope might be an inadequate representation for galaxies whose luminosity profile slope changes smoothly with radius rather than resembling a broken power-law. In fact, we find evidence for an `intermediate' class of galaxies, that cannot unambiguously be classified as either core or power-law galaxies, and which have central cusp slopes and absolute magnitudes intermediate between those of core and power-law galaxies.Comment: 44 pages, 7 Postscript figures. Accepted for publication in the Astronomical Journal. The associated Appendix with figures of luminosity profiles, contour plots and isophotal parameters for all galaxies is available at http://www.astro.washington.edu/rest/centralpro

The FORS Deep Field: Field selection, photometric observations and photometric catalog

The FORS Deep Field project is a multi-colour, multi-object spectroscopic investigation of an approx. 7 times 7 region near the south galactic pole based mostly on observations carried out with the FORS instruments attached to the VLT telescopes. It includes the QSO Q 0103-260 (z = 3.36). The goal of this study is to improve our understanding of the formation and evolution of galaxies in the young Universe. In this paper the field selection, the photometric observations, and the data reduction are described. The source detection and photometry of objects in the FORS Deep Field is discussed in detail. A combined B and I selected UBgRIJKs photometric catalog of 8753 objects in the FDF is presented and its properties are briefly discussed. The formal 50% completeness limits for point sources, derived from the co-added images, are 25.64, 27.69, 26.86, 26.68, 26.37, 23.60 and 21.57 in U, B, g, R, I, J and Ks (Vega-system), respectively. A comparison of the number counts in the FORS Deep Field to those derived in other deep field surveys shows very good agreement.Comment: 15 pages, 11 figures (included), accepted for publication in A&

Rapid Induction of Tumor-specific Type 1 T Helper Cells in Metastatic Melanoma Patients by Vaccination with Mature, Cryopreserved, Peptide-loaded Monocyte-derived Dendritic Cells

There is consensus that an optimized cancer vaccine will have to induce not only CD8+ cytotoxic but also CD4+ T helper (Th) cells, particularly interferon (IFN)-γ–producing, type 1 Th cells. The induction of strong, ex vivo detectable type 1 Th cell responses has not been reported to date. We demonstrate now that the subcutaneous injection of cryopreserved, mature, antigen-loaded, monocyte-derived dendritic cells (DCs) rapidly induces unequivocal Th1 responses (ex vivo detectable IFN-γ–producing effectors as well as proliferating precursors) both to the control antigen KLH and to major histocompatibility complex (MHC) class II–restricted tumor peptides (melanoma-antigen [Mage]-3.DP4 and Mage-3.DR13) in the majority of 16 evaluable patients with metastatic melanoma. These Th1 cells recognized not only peptides, but also DCs loaded with Mage-3 protein, and in case of Mage-3DP4–specific Th1 cells IFN-γ was released even after direct recognition of viable, Mage-3–expressing HLA-DP4+ melanoma cells. The capacity of DCs to rapidly induce Th1 cells should be valuable to evaluate whether Th1 cells are instrumental in targeting human cancer and chronic infections

Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 × 106 DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 × 106 and 12 × 106 DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1–specific CD8+ cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8+ T cell infiltration, whereas nonregressing lesions lacked CD8+ T cells as well as Mage-3 mRNA expression. This study proves the principle that DC “vaccines” can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8+ CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression