NS1 Specific CD8(+) T-Cells with Effector Function and TRBV11 Dominance in a Patient with Parvovirus B19 Associated Inflammatory Cardiomyopathy

Background: Parvovirus B19 (B19V) is the most commonly detected virus in endomyocardial biopsies (EMBs) from patients with inflammatory cardiomyopathy (DCMi). Despite the importance of T-cells in antiviral defense, little is known about the role of B19V specific T-cells in this entity. Methodology and Principal Findings: An exceptionally high B19V viral load in EMBs (115,091 viral copies/mg nucleic acids), peripheral blood mononuclear cells (PBMCs) and serum was measured in a DCMi patient at initial presentation, suggesting B19V viremia. The B19V viral load in EMBs had decreased substantially 6 and 12 months afterwards, and was not traceable in PBMCs and the serum at these times. Using pools of overlapping peptides spanning the whole B19V proteome, strong CD8(+) T-cell responses were elicited to the 10-amico-acid peptides SALKLAIYKA (19.7% of all CD8(+) cells) and QSALKLAIYK (10%) and additional weaker responses to GLCPHCINVG (0.71%) and LLHTDFEQVM (0.06%). Real-time RT-PCR of IFN gamma secretion-assay-enriched T-cells responding to the peptides, SALKLAIYKA and GLCPHCINVG, revealed a disproportionately high T-cell receptor Vbeta (TRBV) 11 expression in this population. Furthermore, dominant expression of type-1 (IFN gamma, IL2, IL27 and Tbet) and of cytotoxic T-cell markers (Perforin and Granzyme B) was found, whereas gene expression indicating type-2 (IL4, GATA3) and regulatory T-cells (FoxP3) was low. Conclusions: Our results indicate that B19V Ag-specific CD8(+) T-cells with effector function are involved in B19V associated DCMi. In particular, a dominant role of TRBV11 and type-1/CTL effector cells in the T-cell mediated antiviral immune response is suggested. The persistence of B19V in the endomyocardium is a likely antigen source for the maintenance of CD8(+) T-cell responses to the identified epitopes

Parallax in “Pi of the Sky” project

The main goal of the “Pi of the Sky” project is search for optical transients (OTs) of astrophysical origin, in particular those related to gamma-ray bursts (GRBs). Since March 2011 the project has two running observatories: one in northern Chile and the other one insouthern Spain. This allows for regular observations of a common sky fields, visible from both observatories which are scheduled usually 1–2 h per night. In such a case, the on-line flash recognition algorithm, looking for optical transients, can use parallax information toassure that events observed from both sites have parallax angle smaller than the error of astrometry. On the other hand, the remaining OT candidates can be verified against a hypothesis of being near-Earth objects. This paper presents algorithm using parallax information for identification of near-Earth objects, which might be satellites, or space debris elements. Preliminary results of the algorithm are also presented

GRB 080319B: A Naked-Eye Stellar Blast from the Distant Universe

Long duration gamma-ray bursts (GRBs) release copious amounts of energy across the entire electromagnetic spectrum, and so provide a window into the process of black hole formation from the collapse of a massive star. Over the last forty years, our understanding of the GRB phenomenon has progressed dramatically; nevertheless, fortuitous circumstances occasionally arise that provide access to a regime not yet probed. GRB 080319B presented such an opportunity, with extraordinarily bright prompt optical emission that peaked at a visual magnitude of 5.3, making it briefly visible with the naked eye. It was captured in exquisite detail by wide-field telescopes, imaging the burst location from before the time of the explosion. The combination of these unique optical data with simultaneous gamma-ray observations provides powerful diagnostics of the detailed physics of this explosion within seconds of its formation. Here we show that the prompt optical and gamma-ray emissions from this event likely arise from different spectral components within the same physical region located at a large distance from the source, implying an extremely relativistic outflow. The chromatic behaviour of the broadband afterglow is consistent with viewing the GRB down the very narrow inner core of a two-component jet that is expanding into a wind-like environment consistent with the massive star origin of long GRBs. These circumstances can explain the extreme properties of this GRB.Comment: 43 pages, 18 figures, 3 tables, submitted to Nature May 11, 200

Incidence of WHO stage 3 and 4 conditions following initiation of Anti-Retroviral Therapy in resource limited settings

To determine the incidence of WHO clinical stage 3 and 4 conditions during early anti-retroviral therapy (ART) in resource limited settings (RLS)

Classification of Light-Induced Desorption of Alkali Atoms in Glass Cells Used in Atomic Physics Experiments

We attempt to provide physical interpretations of light-induced desorption phenomena that have recently been observed for alkali atoms on glass surfaces of alkali vapor cells used in atomic physics experiments. We find that the observed desorption phenomena are closely related to recent studies in surface science, and can probably be understood in the context of these results. If classified in terms of the photon-energy dependence, the coverage and the bonding state of the alkali adsorbates, the phenomena fall into two categories: It appears very likely that the neutralization of isolated ionic adsorbates by photo-excited electron transfer from the substrate is the origin of the desorption induced by ultraviolet light in ultrahigh vacuum cells. The desorption observed in low temperature cells, on the other hand, which is resonantly dependent on photon energy in the visible light range, is quite similar to light-induced desorption stimulated by localized electronic excitation on metallic aggregates. More detailed studies of light-induced desorption events from surfaces well characterized with respect to alkali coverage-dependent ionicity and aggregate morphology appear highly desirable for the development of more efficient alkali atom sources suitable to improve a variety of atomic physics experiments.Comment: 6 pages, 1 figure; minor corrections made, published in e-Journal of Surface Science and Nanotechnology at http://www.jstage.jst.go.jp/article/ejssnt/4/0/4_63/_articl

Prospective Monitoring Reveals Dynamic Levels of T Cell Immunity to Mycobacterium Tuberculosis in HIV Infected Individuals

Monitoring of latent Mycobacterium tuberculosis infection may prevent disease. We tested an ESAT-6 and CFP-10-specific IFN-γ Elispot assay (RD1-Elispot) on 163 HIV-infected individuals living in a TB-endemic setting. An RD1-Elispot was performed every 3 months for a period of 3–21 months. 62% of RD1-Elispot negative individuals were positive by cultured Elispot. Fluctuations in T cell response were observed with rates of change ranging from −150 to +153 spot-forming cells (SFC)/200,000 PBMC in a 3-month period. To validate these responses we used an RD1-specific real time quantitative PCR assay for monokine-induced by IFN-γ (MIG) and IFN-γ inducible protein-10 (IP10) (MIG: r = 0.6527, p = 0.0114; IP-10: r = 0.6967, p = 0.0056; IP-10+MIG: r = 0.7055, p = 0.0048). During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB. Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB. The RD1-Elispot appears to have limited value in this setting

"Pi of the Sky" - all-sky, real-time search for fast optical transients

An apparatus to search for optical flashes in the sky is described. It has been optimized for gamma ray bursts (GRB) optical counterparts. It consists of 2x16 cameras covering all the sky. The sky is monitored continuously and the data are analysed on-line. It has self-triggering capability and can react to external triggers with negative delay. The prototype with two cameras has been installed at Las Campanas (Chile) and is operational from July 2004. The paper presents general idea and describes the apparatus in detail. Performance of the prototype is briefly reviewed and perspectives for the future are outlined

Dual Function of the NK Cell Receptor 2B4 (CD244) in the Regulation of HCV-Specific CD8+ T Cells

The outcome of viral infections is dependent on the function of CD8+ T cells which are tightly regulated by costimulatory molecules. The NK cell receptor 2B4 (CD244) is a transmembrane protein belonging to the Ig superfamily which can also be expressed by CD8+ T cells. The aim of this study was to analyze the role of 2B4 as an additional costimulatory receptor regulating CD8+ T cell function and in particular to investigate its implication for exhaustion of hepatitis C virus (HCV)-specific CD8+ T cells during persistent infection. We demonstrate that (i) 2B4 is expressed on virus-specific CD8+ T cells during acute and chronic hepatitis C, (ii) that 2B4 cross-linking can lead to both inhibition and activation of HCV-specific CD8+ T cell function, depending on expression levels of 2B4 and the intracellular adaptor molecule SAP and (iii) that 2B4 stimulation may counteract enhanced proliferation of HCV-specific CD8+ T cells induced by PD1 blockade. We suggest that 2B4 is another important molecule within the network of costimulatory/inhibitory receptors regulating CD8+ T cell function in acute and chronic hepatitis C and that 2B4 expression levels could also be a marker of CD8+ T cell dysfunction. Understanding in more detail how 2B4 exerts its differential effects could have implications for the development of novel immunotherapies of HCV infection aiming to achieve immune control