PC61 (anti-CD25) treatment inhibits influenza A virus-expanded regulatory T cells and severe lung pathology during a subsequent heterologous lymphocytic choriomeningitis virus infection

Prior immunity to influenza A virus (IAV) in mice changes the outcome to a subsequent lymphocytic choriomeningitis virus (LCMV) infection and can result in severe lung pathology, similar to that observed in patients that died of the 1918 H1N1 pandemic. This pathology is induced by IAV-specific memory CD8(+) T cells cross-reactive with LCMV. Here, we discovered that IAV-immune mice have enhanced CD4(+) Foxp3(+) T-regulatory (Treg) cells in their lungs, leading us to question whether a modulation in the normal balance of Treg and effector T-cell responses also contributes to enhancing lung pathology upon LCMV infection of IAV-immune mice. Treg cell and interleukin-10 (IL-10) levels remained elevated in the lungs and mediastinal lymph nodes (mLNs) throughout the acute LCMV response of IAV-immune mice. PC61 treatment, used to decrease Treg cell levels, did not change LCMV titers but resulted in a surprising decrease in lung pathology upon LCMV infection in IAV-immune but not in naive mice. Associated with this decrease in pathology was a retention of Treg in the mLN and an unexpected partial clonal exhaustion of LCMV-specific CD8(+) T-cell responses only in IAV-immune mice. PC61 treatment did not affect cross-reactive memory CD8(+) T-cell proliferation. These results suggest that in the absence of IAV-expanded Treg cells and in the presence of cross-reactive memory, the LCMV-specific response was overstimulated and became partially exhausted, resulting in a decreased effector response. These studies suggest that Treg cells generated during past infections can influence the characteristics of effector T-cell responses and immunopathology during subsequent heterologous infections. Thus, in humans with complex infection histories, PC61 treatment may lead to unexpected results

Positive-strand RNA viruses—a Keystone Symposia report

Positive-strand RNA viruses have been the cause of several recent outbreaks and epidemics, including the Zika virus epidemic in 2015, the SARS outbreak in 2003, and the ongoing SARS-CoV-2 pandemic. On June 18–22, 2022, researchers focusing on positive-strand RNA viruses met for the Keystone Symposium “Positive-Strand RNA Viruses” to share the latest research in molecular and cell biology, virology, immunology, vaccinology, and antiviral drug development. This report presents concise summaries of the scientific discussions at the symposium

Measurement of event-shape observables in Z→ℓ+ℓ− events in pp collisions at √ s=7 TeV with the ATLAS detector at the LHC

Event-shape observables measured using charged particles in inclusive $Z$-boson events are presented, using the electron and muon decay modes of the $Z$ bosons. The measurements are based on an integrated luminosity of $1.1 {\rm fb}^{-1}$ of proton--proton collisions recorded by the ATLAS detector at the LHC at a centre-of-mass energy $\sqrt{s}=7$ TeV. Charged-particle distributions, excluding the lepton--antilepton pair from the $Z$-boson decay, are measured in different ranges of transverse momentum of the $Z$ boson. Distributions include multiplicity, scalar sum of transverse momenta, beam thrust, transverse thrust, spherocity, and $\mathcal{F}$-parameter, which are in particular sensitive to properties of the underlying event at small values of the $Z$-boson transverse momentum. The Sherpa event generator shows larger deviations from the measured observables than Pythia8 and Herwig7. Typically, all three Monte Carlo generators provide predictions that are in better agreement with the data at high $Z$-boson transverse momenta than at low $Z$-boson transverse momenta and for the observables that are less sensitive to the number of charged particles in the event.Comment: 36 pages plus author list + cover page (54 pages total), 14 figures, 4 tables, submitted to EPJC, All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2014-0

Follow up of GW170817 and its electromagnetic counterpart by Australian-led observing programmes

The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor