scholarly journals Donor-Specific Regulatory T Cell-Mediated Immune Tolerance in an Intrahepatic Murine Allogeneic Islet Transplantation Model with Short-Term Anti-CD154 mAb Single Treatment

2020 ◽  
Vol 29 ◽  
pp. 096368972091387 ◽  
Author(s):  
Seok-Joo Lee ◽  
Hyun-Je Kim ◽  
Na-ri Byun ◽  
Chung-Gyu Park
Keyword(s):  
Islet Transplantation ◽  
Immune Tolerance ◽  
Treg Cells ◽  
Transplantation Tolerance ◽  
Single Treatment ◽  
Short Term ◽  
Donor Skin ◽  
First Time ◽  
Mixed Lymphocyte Reactions ◽  
Transplantation Model

Anti-CD154 blockade-based regimens remain unequaled in prolonging graft survival in various organ transplantation models. Several studies have focused on transplantation tolerance with the anti-CD154 blockade, but none of these studies has investigated the mechanisms associated with its use as the sole treatment in animal models, delaying our understanding of anti-CD154 blockade-mediated immune tolerance. The purpose of this study was to investigate the mechanism underlying the anti-CD154 monoclonal antibody (mAb) blockade in inducing immune tolerance using an intrahepatic murine allogeneic islet transplantation model. Allogeneic BALB/c AnHsd (BALB/c) islets were infused into the liver of diabetic C57BL/6 (B6) mice via the cecal vein. Anti-CD154 mAb (MR1) was administered on −1, 0, 1, 3, 5, and 7 d posttransplantation at 0.5 mg per mouse. We showed that short-term MR1 monotherapy could prolong the allogeneic islet grafts to more than 250 d in the murine intrahepatic islet transplantation model. The second islet grafts transplanted under the kidney capsule of the recipients were protected from rejection. We also found that rejection of same-donor skin grafts transplanted to the tolerant mice was modestly delayed. Using a DEREG mouse model, FoxP3+ regulatory T (Treg) cells were shown to play important roles in transplantation tolerance. In mixed lymphocyte reactions, Treg cells from the tolerant mice showed more potency in suppressing BALB/c splenocyte-stimulated Teff cell proliferation than those from naïve mice. In this study, we demonstrated for the first time that a short-term anti-CD154 mAb single treatment could induce FoxP3+ Treg cell-mediated immune tolerance in the intrahepatic murine allogeneic islet transplantation model.

SAT0278 LOW-DOSE IL-2 RESTORES TREG-MEDIATED IMMUNE TOLERANCE IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1083-1084
Author(s):  
R. Wu ◽  
R. Su ◽  
T. Ding ◽  
H. Xue ◽  
J. An ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Low Dose ◽  
Granulomatosis With Polyangiitis ◽  
Absolute Number ◽  
Treg Cells ◽  
Healthy Controls ◽  
Short Term ◽  
Anca Associated Vasculitis ◽  
T Subsets ◽  
The Absolute

Background:Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of autoimmune disease that can cause systemic organ damage, including granulomatosis with polyangiitis(GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis(EGPA)[1]. Several observations have showed that the breakdown of immune tolerance was involved in the pathogenesis of AAV [2], furthermore, a single, open and clinical trial demonstrates that IL-2 can be used to treat patients with GPA [3]. But there is still a lack of understanding of the relationship between Th17 / Treg and AAV and evidence for the therapeutic effect of IL-2 on AAV, which needs further exploration.Objectives:We first measured the absolute number of CD4+T subsets in peripheral blood of patients to explore the pathogenesis of AAV, and then investigated the effects of short-term and low-dose recombinant human IL-2 (rhIL-2) on CD4+T subsets of patients to analyze the regulatory effect of IL-2 on AAV.Methods:49 patients with AAV, hospitalized at the Second Hospital of Shanxi Medical University from the May 2016 to the November 2019 were enrolled, including 36 patients who were only received conventional glucocorticoids and DMARDs, and other 13 patients who were not only received these treatments but were also injected subcutaneously rhIL-2(50WIU/day for a 5-day course). 31 age and gender-matched healthy adults were selected as controls. The absolute number of Th17 and Treg cells in peripheral blood of health controls and the patients before and after treatment was detected by flow cytometry.Results:There was significant decreased level of Treg cells in the patients with AAV compared with healthy controls (P<0.001) leading to a higher Th17/Treg ratio in the patients with AAV, but there was no statistically significant in the absolute number of Th17 cells between the patients and healthy controls. After the treatment of short-term and low-dose IL-2, there was a significant increase in the absolute number of Treg cells (P<0.01) leading to a decrease in the ratio of Th17 and Treg (p<0.05).The absolute number of Th17 had a trend towards higher values but was not statistical significance.Conclusion:The difference of Treg cells between the patients and healthy controls suggested that the decreased number of Treg cells failed to control autoimmune inflammatory response contributing to the pathogenesis of AAV. After the treatment of short-term and low-dose rhIL-2, there was a more significant increase in the absolute number of Treg cells showing that IL-2 could selectively stimulate the growth of Treg cells and restore the Treg-mediated immune tolerance in patients with AAV to achieve disease remission.References:[1]Cosmi, L.,Th17 and Treg lymphocytes as cellular biomarkers of disease activity in Granulomatosis with Polyangiitis.Eur J Immunol, 2017.47(4): p. 633-636.[2]Pagnoux, C.,Updates in ANCA-associated vasculitis.Eur J Rheumatol, 2016.3: p. 122-133.[3]Rosenzwajg, M., et al.,Immunological and clinical effects of low-dose interleukin-2 across 11 autoimmune diseases in a single, open clinical trial.Annals of the Rheumatic Diseases, 2019.78(2): p. 209-217.Disclosure of Interests:None declared

Insulin-mimetic effects of short-term Rapamycin in type 1 diabetic patients prior islet transplantation

2017 ◽  
Author(s):  
Federica Ermetici ◽  
Silvia Briganti ◽  
Stefano Benedini ◽  
Roberto Codella ◽  
Paola Maffi ◽  
...  
Keyword(s):  
Islet Transplantation ◽  
Diabetic Patients ◽  
Short Term ◽  
Insulin Mimetic ◽  
Type 1 Diabetic Patients

Regulating short-term rentals: Joined cases C-724/18 and C-727/18 Cali Apartments

2021 ◽  
pp. 1023263X2110146
Author(s):  
Tania Pantazi
Keyword(s):  
Consumer Protection ◽  
European Court Of Justice ◽  
Short Term ◽  
European Regulation ◽  
Future Developments ◽  
Online Platforms ◽  
Court Of Justice ◽  
European Court ◽  
Tourist Accommodation ◽  
First Time

The increase in short-term rentals via online platforms has captured the attention of scholars and regulators. Short-term letting is now considered a considerable alternative to traditional tourist accommodation contracts, challenging matters such as conditions in the housing market and consumer protection. Online platforms, such as Airbnb, Booking.com , Expedia and Tripadvisor, now provide offers for short-term accommodation contracts along with traditional accommodation options (hotels, hostels, apartments). The recent decision of the European Court of Justice in Joined cases C-724/18 and C-727/18 addresses for the first time the issue of regulation of short-term rentals in Member States and evaluates a national authorization scheme in light of the Services Directive. The present paper provides a brief background of European regulation affecting short-term rentals and discusses the judgment and its implications for future developments.

scholarly journals A SLR Pre-Processing Algorithm Based on Satellite Signature Effect

2021 ◽  
Vol 11 (19) ◽  
pp. 8880
Author(s):  
Bowen Guan ◽  
Cunbo Fan ◽  
Ning An ◽  
Ricardo Cesar Podesta ◽  
Dra Ana Pacheco ◽  
...  
Keyword(s):  
Mean Value ◽  
Observation Data ◽  
Short Term ◽  
Error Sources ◽  
Effect Model ◽  
The Mean ◽  
The Stability ◽  
First Time ◽  
Satellite Signature Effect

As one of the major error sources, satellite signature effect should be reduced or even erased from the distribution of the post-fit residuals to improve the ranging precision. A simulation of satellite signature effect removal process for normal point algorithm is conducted based on a revised model of satellite response, which fully considers the structural and distribution characteristics of retroreflectors. In order to eliminate both long-term and short-term satellite signature effect, a clipping method for SLR data processing is proposed by defining the clipping location as 5.6 mm away from the mean value of the long-term fit residuals to select effective returns for normal points. The results indicate that, compared to normal points algorithm, the RMS per NP of LAGEOS-1 observation data processed by the clipping method is reduced from 62.90 ± 9.9 mm to 56.07 ± 4.69 mm, and the stability of RMS is improved 53%. This study improves the satellite signature effect model and simulates the fluctuation of normal points caused by satellite signature effect for the first time. The new method based on the simulation of satellite signature effect has stronger robustness and applicability, which can further minimize the influence of satellite signature effect on the SLR production and significantly improve the data property.

scholarly journals Experimental evidence for foraminiferal calcification under anoxia

2014 ◽  
Vol 11 (14) ◽  
pp. 4029-4038 ◽  
Author(s):  
M. P. Nardelli ◽  
C. Barras ◽  
E. Metzger ◽  
A. Mouret ◽  
H. L. Filipsson ◽  
...  
Keyword(s):  
Environmental Variability ◽  
Sediment Cores ◽  
Adult Mortality ◽  
Short Term ◽  
Essential Information ◽  
Ample Evidence ◽  
Anoxic Conditions ◽  
Inhibition Of Growth ◽  
Foraminiferal Species ◽  
First Time

Abstract. Benthic foraminiferal tests are widely used for paleoceanographic reconstructions from a range of different environments with varying dissolved oxygen concentrations in the bottom water. There is ample evidence that foraminifera can live in anoxic sediments. For some species, this is explained by a switch to facultative anaerobic metabolism (i.e. denitrification). Here we show for the first time that adult specimens of three benthic foraminiferal species are not only able to survive, but are also able to calcify under anoxic conditions, at various depths in the sediment, and with or without nitrates. In fact, several specimens of Ammonia tepida (1–4%), Bulimina marginata (8–24%) and Cassidulina laevigata (16–23%) were able to calcify at different redox fronts of sediment cores, under laboratory conditions. This demonstrates ongoing metabolic processes, even in micro-environments where denitrification is not possible. Earlier observations suggest that the disappearance of foraminiferal communities after prolonged anoxia is not due to instantaneous or strongly increased adult mortality. Here we show that it cannot be explained by an inhibition of growth through chamber addition either. Our observations of ongoing calcification under anoxic conditions mean that geochemical proxy data obtained from benthic foraminifera in settings experiencing intermittent anoxia have to be reconsidered. The analysis of whole single specimens or of their successive chambers may provide essential information about short-term environmental variability and/or the causes of anoxia.

scholarly journals Adenovirus-Mediated CCR7 and BTLA Overexpression Enhances Immune Tolerance and Migration in Immature Dendritic Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Haiming Xin ◽  
Jinhong Zhu ◽  
Hongcheng Miao ◽  
Zhenyu Gong ◽  
Xiaochen Jiang ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Tolerance ◽  
Transplant Recipients ◽  
T Helper ◽  
T Helper 2 ◽  
Immature Dendritic Cells ◽  
And Migration ◽  
Mixed Lymphocyte Reactions ◽  
Dc Maturation

Our previous report revealed that immature dendritic cells (imDCs) with adenovirus-mediated CCR7 overexpression acquired an enhanced migratory ability but also exhibited the lower immune tolerance observed in more mature cells. In the present study, we aimed to investigate whether BTLA overexpression was sufficient to preserve immune tolerance in imDCs with exogenous CCR7 overexpression. Scanning electron microscopy and surface antigens analysis revealed that BTLA overexpression suppressed DC maturation, an effect further potentiated in CCR7 and BTLA cooverexpressing cells. Correspondingly, in vitro chemotaxis assays and mixed lymphocyte reactions demonstrated increased migratory potential and immune tolerance in CCR7 and BTLA coexpressing cells. Furthermore, CCR7 and BTLA cooverexpressed imDCs suppressed IFN-γ and IL-17 expression and promoted IL-4 and TGF-beta expression of lymphocyte, indicating an increase of T helper 2 (Th2) regulatory T cell (Treg). Thus, these data indicate that CCR7 and BTLA cooverexpression imparts an intermediate immune phenotype in imDCs when compared to that in CCR7- or BTLA-expressing counterparts that show a more immunocompetent or immunotolerant phenotype, respectively. All these results indicated that adenovirus-mediated CCR7 and BTLA overexpression could enhance immune tolerance and migration of imDCs. Our study provides a basis for further studies on imDCs in immune tolerance, with the goal of developing effective cellular immunotherapies for transplant recipients.

Short-Term Training in Mindfulness Predicts Helping Behavior Toward Racial Ingroup and Outgroup Members

2021 ◽  
pp. 194855062110530
Author(s):  
Daniel R. Berry ◽  
Catherine S. J. Wall ◽  
Justin D. Tubbs ◽  
Fadel Zeidan ◽  
Kirk Warren Brown
Keyword(s):  
Controlled Trial ◽  
Helping Behavior ◽  
Mindfulness Training ◽  
Trait Mindfulness ◽  
Short Term ◽  
Randomized Controlled ◽  
Ecological Momentary ◽  
First Time ◽  
Momentary Assessment

A randomized controlled trial tested whether mindfulness training would increase lab-based and in vivo spontaneous helping behaviors toward racial outgroup members. First, across conditions, those scoring higher in baseline trait mindfulness showed higher levels of preintervention lab-based and ecological momentary assessment (EMA)-based helping behavior. Next, short-term (4-day) training in mindfulness, relative to a well-matched sham meditation training, increased interracial helping behavior in a lab-based simulation. Finally, among people scoring lower in a basic form of trait mindfulness at baseline—that is, with greater room for improvement—mindfulness training predicted higher postintervention in vivo helping behavior reported via EMA. However, neither training condition alone attenuated preferential helping toward racial ingroup members. These findings indicate, for the first time, that mindfulness and its training fosters helping behavior toward strangers and acquaintances regardless of their racial ingroup or outgroup status, but preferential helping of racial ingroup members remains.

Learning from a Frozen Ocean: The Changing Face of Antarctic Ocean Ecology

2016 ◽  
Author(s):  
Hugh W. Ducklow
Keyword(s):  
Research Collaboration ◽  
Scientific Work ◽  
Principal Investigator ◽  
Rate Of Change ◽  
Short Term ◽  
Temporal Perspective ◽  
Ocean Science ◽  
Long Term Ecological Research ◽  
History Of ◽  
First Time

The temporal perspective provided by the Long-Term Ecological Research (LTER) program places individual, limited, short-term observations and experiments in a valuable context. Proper interpretation of short-term results may be incomplete without a longer-term perspective. This often makes me skeptical of individual studies. The remote location and harsh environment of Antarctica place special demands and constraints on research, collaboration, and education. Meeting these challenges is one of the most exhilarating aspects of our LTER project. Keeping the proper balance between maintaining continuity of observations and keeping the research program new and innovative is another key challenge for research in the LTER program. But rather than constraining them, the ongoing nature of the LTER program facilitates and enhances creative observations and innovation. In 2001, I joined the LTER network as lead principal investigator for the Palmer LTER project (PAL), one of two pelagic marine sites in the LTER network. That was my first formal exposure to the LTER program, about midway through my scientific career. After majoring in the history of science in college, I received my PhD in environmental engineering from Harvard in 1977. I was originally trained as an environmental microbiologist and gradually evolved into a biological oceanographer and ocean biogeochemist. Prior to joining PAL, I worked in other large, multidisciplinary, and interdisciplinary ocean science programs. In addition to leading PAL, I study the roles of ocean microbes in the biogeochemical cycling of carbon and other elements in the ice-influenced ocean surrounding Antarctica. As a principal investigator, I participate in planning and guiding the LTER network. Network participation has significantly broadened my perspective on my own personal scientific work. This participation has been one of my more interesting and fulfilling experiences as a scientist. Over the past 20 years, research has shown that the western Antarctic Peninsula is one of the most rapidly warming regions on earth, and we are gradually beginning to understand how the ecosystem is responding to this unprecedented rate of change. Joining PAL changed my life. (Actually, going to Antarctica for the first time changed my life, but the LTER program gave me the opportunity to go there every year.)

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