Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality

Programmed death ligand-1 (PD-L1) interaction with PD-1 induces T cell exhaustion and is a therapeutic target to enhance immune responses against cancer and chronic infections. In murine bone marrow transplant models, PD-L1 expression on host target tissues reduces the incidence of graft-versus-host disease (GVHD). PD-L1 is also expressed on T cells; however, it is unclear whether PD-L1 on this population influences immune function. Here, we examined the effects of PD-L1 modulation of T cell function in GVHD. In patients with severe GVHD, PD-L1 expression was increased on donor T cells. Compared with mice that received WT T cells, GVHD was reduced in animals that received T cells from Pdl1–/– donors. PD-L1–deficient T cells had reduced expression of gut homing receptors, diminished production of inflammatory cytokines, and enhanced rates of apoptosis. Moreover, multiple bioenergetic pathways, including aerobic glycolysis, oxidative phosphorylation, and fatty acid metabolism, were also reduced in T cells lacking PD-L1. Finally, the reduction of acute GVHD lethality in mice that received Pdl1–/– donor cells did not affect graft-versus-leukemia responses. These data demonstrate that PD-L1 selectively enhances T cell–mediated immune responses, suggesting a context-dependent function of the PD-1/PD-L1 axis, and suggest selective inhibition of PD-L1 on donor T cells as a potential strategy to prevent or ameliorate GVHD

Revised nomenclature for the mammalian long-chain acyl-CoA synthetase gene family: TABLE 1.

By consensus, the acyl-CoA synthetase (ACS) community, with the advice of the human and mouse genome nomenclature committees, has revised the nomenclature for the mammalian long-chain acyl-CoA synthetases. ACS is the family root name, and the human and mouse genes for the long-chain ACSs are terme

Chasing Gravitational Waves with the Cherenkov Telescope Array

The detection of gravitational waves (GWs) from a binary neutron star (BNS) merger by Advanced LIGO and Advanced Virgo (GW170817), along with the discovery of the electromagnetic counterparts of this GW event, ushered in a new era of multimessenger astronomy, providing the first direct evidence that BNS mergers are progenitors of short gamma-ray bursts (GRBs). Such events may also produce very-high-energy (VHE, > 100GeV) photons which have yet to be detected in coincidence with a GW signal. The Cherenkov Telescope Array (CTA) is a next-generation VHE observatory which aims to be indispensable in this search, with an unparalleled sensitivity and ability to slew anywhere on the sky within a few tens of seconds. Achieving such a feat will require a comprehensive real-time strategy capable of coordinating searches over potentially very large regions of the sky. This work will evaluate and provide estimations on the number of GW-CTA events determined from simulated BNS systems and short GRBs, considering both on- and off-axis emission. In addition, we will present and discuss the prospects of potential follow-up strategies with CTA

Performance update of an event-type based analysis for the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) will be the next-generation observatory in the field of very-high-energy (20 GeV to 300 TeV) gamma-ray astroparticle physics. The traditional approach to data analysis in this field is to apply quality cuts, optimized using Monte Carlo simulations, on the data acquired to maximize sensitivity. Subsequent steps of the analysis typically use the surviving events to calculate one set of instrument response functions (IRFs) to physically interpret the results. However, an alternative approach is the use of event types, as implemented in experiments such as the Fermi-LAT. This approach divides events into sub-samples based on their reconstruction quality, and a set of IRFs is calculated for each sub-sample. The sub-samples are then combined in a joint analysis, treating them as independent observations. In previous works we demonstrated that event types, classified using Machine Learning methods according to their expected angular reconstruction quality, have the potential to significantly improve the CTA angular and energy resolution of a point-like source analysis. Now, we validated the production of event-type wise full-enclosure IRFs, ready to be used with science tools (such as Gammapy and ctools). We will report on the impact of using such an event-type classification on CTA high-level performance, compared to the traditional procedure

Expected exclusion limits to TeV dark matter from the Perseus Cluster with the Cherenkov Telescope Array

Clusters of galaxies are the largest gravitationally-bound structures in the Universe. They are composed of galaxies and gas (approximately 15% of the total mass) mostly dark matter (DM, accounts up to 85% of the total mass). If the DM is composed of Weakly Interacting Massive Particles (WIMPs), galaxy clusters represent one of the best targets to search for gamma-ray signals induced by the decay of WIMPs, with masses around the TeV scale. Due to its sensitivity and energy range of operation (from 20 GeV to 300 TeV), the Cherenkov Telescope Array (CTA) Observatory has a unique opportunity to test WIMPs with masses close to the unitarity limit. This will complement the searches for DM from other gamma-ray observatories as well as direct and collider experiments. The CTA Observatory is planning to search for gamma-ray emission, either its origin may be cosmic-ray (CR) or DM related, in the Perseus galaxy cluster during the first years of operation. In this poster, we will present the software created to perform the analysis using the ctools software and the corresponding results

Sensitivity of the Cherenkov Telescope Array to the gamma-ray emission from neutrino sources detected by IceCube

Gamma-ray observations of the astrophysical neutrino sources are fundamentally important for understanding the underlying neutrino production mechanism. We investigate the Cherenkov Telescope Array (CTA) ability to detect the very-high-energy (VHE) gamma-ray counterparts to the neutrino-emitting Active Galaxies. The CTA performance under different configurations and array layouts is computed based on the neutrino and gamma-ray simulations of steady and transient types of sources, assuming that the neutrino events are detected with the IceCube neutrino telescope. The CTA detection probability is calculated for both CTA sites taking into account the visibility constraints. We find that, under optimal observing conditions, CTA could observe the VHE gamma-ray emission from at least 3 neutrino events per year