In vivo dynamics and adaptation of HTLV-1-infected clones under different clinical conditions.

Human T-cell leukemia virus type 1 (HTLV-1) spreads through cell contact. Therefore, this virus persists and propagates within the host by two routes: clonal proliferation of infected cells and de novo infection. The proliferation is influenced by the host immune responses and expression of viral genes. However, the detailed mechanisms that control clonal expansion of infected cells remain to be elucidated. In this study, we show that newly infected clones were strongly suppressed, and then stable clones were selected, in a patient who was infected by live liver transplantation from a seropositive donor. Conversely, most HTLV-1+ clones persisted in patients who received hematopoietic stem cell transplantation from seropositive donors. To clarify the role of cell-mediated immunity in this clonal selection, we suppressed CD8+ or CD16+ cells in simian T-cell leukemia virus type 1 (STLV-1)-infected Japanese macaques. Decreasing CD8+ T cells had marginal effects on proviral load (PVL). However, the clonality of infected cells changed after depletion of CD8+ T cells. Consistent with this, PVL at 24 hours in vitro culture increased, suggesting that infected cells with higher proliferative ability increased. Analyses of provirus in a patient who received Tax-peptide pulsed dendritic cells indicate that enhanced anti-Tax immunity did not result in a decreased PVL although it inhibited recurrence of ATL. We postulate that in vivo selection, due to the immune response, cytopathic effects of HTLV-1 and intrinsic attributes of infected cells, results in the emergence of clones of HTLV-1-infected T cells that proliferate with minimized HTLV-1 antigen expression

Additional file 1: of Optimal regimens of sulfamethoxazole-trimethoprim for chemoprophylaxis of Pneumocystis pneumonia in patients with systemic rheumatic diseases: results from a non-blinded, randomized controlled trial

List of ethics committees that approved this study. (DOCX 13 kb

Concept design of the LiteBIRD satellite for CMB B-mode polarization

LiteBIRD is a candidate for JAXA's strategic large mission to observe the cosmic microwave background (CMB) polarization over the full sky at large angular scales. It is planned to be launched in the 2020s with an H3 launch vehicle for three years of observations at a Sun-Earth Lagrangian point (L2). The concept design has been studied by researchers from Japan, U.S., Canada and Europe during the ISAS Phase-A1. Large scale measurements of the CMB B-mode polarization are known as the best probe to detect primordial gravitational waves. The goal of LiteBIRD is to measure the tensor-to-scalar ratio (r) with precision of r < 0:001. A 3-year full sky survey will be carried out with a low frequency (34 - 161 GHz) telescope (LFT) and a high frequency (89 - 448 GHz) telescope (HFT), which achieve a sensitivity of 2.5 \u3bcK-arcmin with an angular resolution 30 arcminutes around 100 GHz. The concept design of LiteBIRD system, payload module (PLM), cryo-structure, LFT and verification plan is described in this paper