Stimulation of lymphokine release from T lymphoblasts: Requirement for mRNA synthesis and inhibition by cyclosporin A

[No abstract available

Dendritic cells induce T lymphocytes to release B cell-stimulating factors by an interleukin 2-dependent mechanism

[No abstract available

Virus replication begins in dendritic cells during the transmission of HIV-1 from mature dendritic cells to T cells

Background: To initiate immunity, dendritic cells (DCs) capture antigens or viruses at body surfaces, undergo maturation to express T-cell costimulatory molecules, and then migrate to lymphoid organs. DCs at body surfaces can capture human immunodeficiency virus 1 (HIV-1), but mature DCs do not support replication of the virus unless T cells are added. The initial site for HIV-1 replication remains unknown and it is unclear whether replication can take place in DCs or whether the virus must first be transmitted from DCs to T cells. Results: We generated mature DCs from monocyte precursors. Upon infection with HIV-1, reverse transcription was completed only when T cells were added. When the reverse transcriptase inhibitor azidothymidine was added to the DCs during exposure to HIV-1, the DCs remained fully infectious, as long as the drug was removed just before culturing the DCs with T cells. HIV-1 variants that were engineered to undergo only one cycle of replication were able to infect DCs and replicate once in these cells. When T cells were added, newly produced HIV-1 Gag protein was exclusively localized to the DCs. With wild-type virus, subsequent rounds of replication took place in T cells. Soluble CD40 ligand (CD40L) and CD40L-transfected fibroblasts stimulated HIV-1 replication in purified mature DCs. Conclusions: Mature DCs provide a drug-resistant reservoir for HIV-1. This reservoir is activated within DCs by CD40L and upon interaction with T cells, and the virus then spreads rapidly to other T cells

The Effect of Immunosuppressive Agents on the Induction of Nuclear Factors that Bind to Sites on the Interleukin 2 Promoter

Cyclosporin A (CSA), FK506, and glucocorticosteroids all inhibit the production of lymphokines by decreasing lymphokine gene expression. Previous experiments have defined six different sites that may contribute to the transcriptional control of the interleukin 2 (IL2) promoter, and for each, active nuclear binding factors are induced upon mitogenic stimulation. While dexamethasone markedly blocks the increase in IL2 mRNA in stimulated human blood T cells, we found that the drug does not block the appearance of factors that bind to the transcriptional control sites termed AP-1, AP-3, NF-kB, OCT1, B site, and NF-AT. In contrast, both CSA and FK506 have similar effects : the drugs cause modest decreases in AP-3 and NF-kB, and marked decreases in the activity of AP-1 and NF-AT Therefore, CSA and FK506, while chemically different, seem to act upon a similar pathway that leads to IL2 gene expression, whereas glucocorticoids do not affect this pathway

Multiparametric Mri in the Management of Prostate Cancer: an Update-A Narrative Review

The growing interest in multiparametric MRI is leading to important changes in the diagnostic process of prostate cancer. MRI-targeted biopsy is likely to become a standard for the diagnosis of prostate cancer in the next years. Despite it is well known that MRI has no role as a staging technique, it is clear that multiparametric MRI may be of help in active surveillance protocols. Noteworthy, MRI in active surveillance is not recommended, but a proper understanding of its potential may be of help in achieving the goals of a delayed treatment strategy. Moreover, the development of minimally invasive techniques, like laparoscopic and robotic surgery, has led to greater expectations as regard to the functional outcomes of radical prostatectomy. Multiparametric MRI may play a role in planning surgical strategies, with the aim to provide the highest oncologic outcome with a minimal impact on the quality of life. We maintain that a proper anatomic knowledge of prostate lesions may allow the surgeon to achieve a better result in planning as well as in performing surgery and help the surgeon and the patient engage in a shared decision in planning a more effective strategy for prostate cancer control and treatment. This review highlights the advantages and the limitations of multiparametric MRI in prostate cancer diagnosis, in active surveillance and in planning surgery

APOBEC3G/3F mediates intrinsic resistance of monocyte-derived dendritic cells to HIV-1 infection

HIV-1 infects immature dendritic cells (iDCs), but infection is inefficient compared with activated CD4+ T cells and only involves a small subset of iDCs. We analyzed whether this could be attributed to specific cellular restrictions during the viral life cycle. To study env-independent restriction to HIV-1 infection, we used a single-round infection assay with HIV-1 pseudotyped with vesicular stomatitis virus G protein (HIV-VSVG). Small interfering RNA–mediated depletion of APOBEC3G/3F (A3G/3F), but not TRIM5α, enhanced HIV-1 infection of iDCs, indicating that A3G/3F controls the sensitivity of iDCs to HIV-1 infection. Furthermore, sequences of HIV reverse transcripts revealed G-to-A hypermutation of HIV genomes during iDC infection, demonstrating A3G/3F cytidine deaminase activity in iDCs. When we separated the fraction of iDCs that was susceptible to HIV, we found the cells to be deficient in A3G messenger RNA and protein. We also noted that during DC maturation, which further reduces susceptibility to infection, A3G levels increased. These findings highlight a role for A3G/3F in explaining the resistance of most DCs to HIV-1 infection, as well as the susceptibility of a fraction of iDCs. An increase in the A3G/3F-mediated intrinsic resistance of iDCs could result in a block of HIV infection at its mucosal point of entry

'Cyanidin volumetric index' and 'chromaticity coordinates ratio' to characterize red raspberry (Rubus idaeus)

The object of this work is presented in a larger research project concerning ‘New indexes to evidence the nutritional quality of small fruits’ in progress at the Analytical Food Research Laboratories, University of Milan. The present paper contains data that contribute to the analytical characterization of 12 varieties of red raspberry through the high-performance liquid chromatography determination of the aglycon ‘cyanidin’ derived from chemical hydrolysis of berries. Even more interesting results are the proposal of the ‘cyanidin volumetric index’, by which it is possible to compare different red raspberry varieties with higher meaningfulness. A new possible correlation between the ratio of chromaticity coordinates ‘a/b’ and the cyanidin content of red raspberries has been identified

Online Monitoring of the Osiris Reactor with the Nucifer Neutrino Detector

Originally designed as a new nuclear reactor monitoring device, the Nucifer detector has successfully detected its first neutrinos. We provide the second shortest baseline measurement of the reactor neutrino flux. The detection of electron antineutrinos emitted in the decay chains of the fission products, combined with reactor core simulations, provides an new tool to assess both the thermal power and the fissile content of the whole nuclear core and could be used by the Inter- national Agency for Atomic Energy (IAEA) to enhance the Safeguards of civil nuclear reactors. Deployed at only 7.2m away from the compact Osiris research reactor core (70MW) operating at the Saclay research centre of the French Alternative Energies and Atomic Energy Commission (CEA), the experiment also exhibits a well-suited configuration to search for a new short baseline oscillation. We report the first results of the Nucifer experiment, describing the performances of the 0.85m3 detector remotely operating at a shallow depth equivalent to 12m of water and under intense background radiation conditions. Based on 145 (106) days of data with reactor ON (OFF), leading to the detection of an estimated 40760 electron antineutrinos, the mean number of detected antineutrinos is 281 +- 7(stat) +- 18(syst) electron antineutrinos/day, in agreement with the prediction 277(23) electron antineutrinos/day. Due the the large background no conclusive results on the existence of light sterile neutrinos could be derived, however. As a first societal application we quantify how antineutrinos could be used for the Plutonium Management and Disposition Agreement.Comment: 22 pages, 16 figures - Version

Intensified and protective CD4+ T cell immunity in mice with anti–dendritic cell HIV gag fusion antibody vaccine

Current human immunodeficiency virus (HIV) vaccine approaches emphasize prime boost strategies comprising multiple doses of DNA vaccine and recombinant viral vectors. We are developing a protein-based approach that directly harnesses principles for generating T cell immunity. Vaccine is delivered to maturing dendritic cells in lymphoid tissue by engineering protein antigen into an antibody to DEC-205, a receptor for antigen presentation. Here we characterize the CD4+ T cell immune response to HIV gag and compare efficacy with other vaccine strategies in a single dose. DEC-205–targeted HIV gag p24 or p41 induces stronger CD4+ T cell immunity relative to high doses of gag protein, HIV gag plasmid DNA, or recombinant adenovirus-gag. High frequencies of interferon (IFN)-γ– and interleukin 2–producing CD4+ T cells are elicited, including double cytokine-producing cells. In addition, the response is broad because the primed mice respond to an array of peptides in different major histocompatibility complex haplotypes. Long-lived T cell memory is observed. After subcutaneous vaccination, CD4+ and IFN-γ–dependent protection develops to a challenge with recombinant vaccinia-gag virus at a mucosal surface, the airway. We suggest that a DEC-targeted vaccine, in part because of an unusually strong and protective CD4+ T cell response, will improve vaccine efficacy as a stand-alone approach or with other modalities