Kinetics of IL-7 and IL-15 Levels after Allogeneic Peripheral Blood Stem Cell Transplantation following Nonmyeloablative Conditioning

Background: We analysed kinetics of IL-7 and IL-15 levels in 70 patients given peripheral blood stem cells after nonmyeloablative conditioning. Methods: EDTA-anticoagulated plasma and serum samples were obtained before conditioning and about once per week after transplantation until day 100. Samples were aliquoted and stored at 280uC within 3 hours after collection until measurement of cytokines. IL-7 and IL-15 levels were measured by ELISAs. Results: Median IL-7 plasma levels remained below 6 pg/L throughout the first 100 days, although IL-7 plasma levels were significantly higher on days 7 (5.1 pg/mL, P = 0.002), 14 (5.2 pg/mL, P,0.001), and 28 (5.1 pg/mL, P = 0.03) (but not thereafter) than before transplantation (median value of 3.8 pg/mL). Median IL-15 serum levels were significantly higher on days 7 (12.5 pg/mL, P,0.001), 14 (10.5 pg/mL, P,0.001), and 28 (6.2 pg/mL, P,0.001) than before transplantation (median value of 2.4 pg/mL). Importantly, IL-7 and IL-15 levels on days 7 or 14 after transplantation did not predict grade II–IV acute GVHD. Conclusions: These data suggest that IL-7 and IL-15 levels remain relatively low after nonmyeloablative transplantation, and that IL-7 and IL-15 levels early after nonmyeloablative transplantation do not predict for acute GVHD

Thinking out of the box - New approaches to controlling GVHD

Graft-versus-host disease (GVHD) remains a major limitation of allogeneic hematopoietic cell transplantation (allo-HCT). Despite major advances in the understanding of GVHD pathogenesis, standard GVHD prophylaxis regimens continue to bebased on the combination of a calcineurin inhibitor with an antimetabolite, while first line treatmentsstill relies on high-dose corticosteroids. Further, no second line treatment has emerged thus far in acute or chronic GVHD patients who failed on corticosteroids. After briefly reviewing current standards of GVHD prevention and treatment, this article will discuss recent approaches that might change GVHD prophylaxis / treatment in the next decades, with a special focus on recently developed immunoregulatory strategies based on infusion of mesenchymal stromal or regulatory T-cells, or on injection of lowdose interleukin-2

Imatinib mesylate inhibits STAT5 phosphorylation in response to IL-7 and promotes T cell lymphopenia in chronic myelogenous leukemia patients

AbstractImatinib mesylate (IM) therapy has been shown to induce lower T cell counts in chronic myelogenous leukemia (CML) patients and an interference of IM with T cell receptor (TCR) signaling has been invoked to explain this observation. However, IL-7 and TCR signaling are both essential for lymphocyte survival. This study was undertaken to determine whether IM interferes with IL-7 or TCR signaling to explain lower T cell counts in patients. At diagnosis, CML patients have typically lower CD4+ counts in their blood, yet CD8+ counts are normal or even increased in some. Following the initiation of IM treatment, CD4+ counts were further diminished and CD8+ T lymphocytes were dramatically decreased. In vitro studies confirmed IM interference with TCR signaling through the inhibition of ERK phosphorylation and we showed a similar effect on IL-7 signaling and STAT5 phosphorylation (STAT5-p). Importantly however, using an in vivo mouse model, we demonstrated that IM impaired T cell survival through the inhibition of IL-7 and STAT5-p but not TCR signaling which remained unaffected during IM therapy. Thus, off-target inhibitory effects of IM on IL-7 and STAT5-p explain how T cell lymphopenia occurs in patients treated with IM.</jats:p

Correction: Imatinib mesylate inhibits STAT5 phosphorylation in response to IL-7 and promotes T cell lymphopenia in chronic myelogenous leukemia patients

A correction to this paper has been published and can be accessed via a link at the top of the paper.</jats:p

Tiling an Interval of the Discrete Line

Solve a conjecture concerning two integer sequences referenced in the Encyclopedia of Integer Sequences as A107736 and A067824: these two sequences are in fact identical.International audienceWe consider the problem of tiling a segment {0, . . . , n} of the discrete line. More precisely, we ought to characterize the structure of the patterns that tile a segment and their number. A pattern is a subset of N. A tiling pattern or tile for {0, . . . , n} is a subset A P(N) such that there exists B P(N) and such that the direct sum of A and B equals {0, . . . , n}. This problem is related to the di cult question of the decomposition in direct sums of the torus Z/nZ (proposed by Minkowski). Using combinatorial and algebraic techniques, we give a new elementary proof of Krasner factorizations. We combinatorially prove that the tiles are direct sums of some arithmetic sequences of speci c lengths. Besides, we show there are as many tiles whose smallest tilable segment is {0, . . . , n} as tiles whose smallest tilable segment is {0, . . . , d}, for all strict divisors d of n. This enables us to exhibit an optimal linear time algorithm to compute for a given pattern the smallest segment that it tiles if any, as well as a recurrence formula for counting the tiles of a segment

Dip-coated screen for gain calibration and alignment of gamma-ray telescope mirrors

In this communication, we will present a dual-purpose calibration system of NectarCAM, a medium-size-telescope camera proposed for the Cherenkov Telescope Array (CTA). The device is based on a white diffuse-reflective screen mounted on an XY motorization to reach every location in the focal plane, including a parking position when not in use. The design of the system was led by the requirements to perform the mirror alignment and the study of the telescope Point Spread Function (PSF) on one side (A), and to calibrate the photodetection chains (one for each of the 1855 photomultiplier tubes) of the camera in single photoelectron mode on the other side (B). The main requirement for the calibration device consists in producing a high-reflective (> 90% between 450 nm and 700 nm) and diffusive (following Lambert's cosine law) surface for side A. The other side, B, should emit an homogeneous amount of light over the surface. To satisfy these requirements, we developed a unique screen made out of PMMA and coated with the BC-620 paint from Saint-Gobain. For single-photoelectron calibration purposes, light is produced by a pulsed light source and injected into the screen via a fishtail light guide. We studied the optimal screen shape, paint, and painting process. To do so, we produced several prototypes and compared the light output intensity over the screen surface. These studies led to the definition of a specific painting pattern that enhances the light emission uniformity over the final octagonal screen surface. After having briefly described the developed prototypes that led to the current calibration device, we will focus on the calibration system performances and will describe the dip-coating application process, which is an essential technique to achieve reliable and reproducible optical performances