CD28 Costimulation Is Required for In Vivo Induction of Peripheral Tolerance in CD8 T Cells

Whereas ligation of CD28 is known to provide a critical costimulatory signal for activation of CD4 T cells, the requirement for CD28 as a costimulatory signal during activation of CD8 cells is less well defined. Even less is known about the involvement of CD28 signals during peripheral tolerance induction in CD8 T cells. In this study, comparison of T cell responses from CD28-deficient and CD28 wild-type H-Y–specific T cell receptor transgenic mice reveals that CD8 cells can proliferate, secrete cytokines, and generate cytotoxic T lymphocytes efficiently in the absence of CD28 costimulation in vitro. Surprisingly, using pregnancy as a model to study the H-Y–specific response of maternal T cells in the presence or absence of CD28 costimulation in vivo, it was found that peripheral tolerance does not occur in CD28KO pregnants in contrast to the partial clonal deletion and hyporesponsiveness of remaining T cells observed in CD28WT pregnants. These data demonstrate for the first time that CD28 is critical for tolerance induction of CD8 T cells, contrasting markedly with CD28 independence of in vitro activation, and suggest that the role of CD28/B7 interactions in peripheral tolerance of CD8 T cells may differ significantly from that of CD4 T cells

Beta-glucan reflects liver injury after preservation and transplantation in dogs.

Graft failure and extrahepatic organ complications, which frequently develop after transplantation, may be related to inflammatory mediators stimulated by endotoxin (ET). The role of endotoxemia after liver transplantation is controversial and may depend upon differences in the ET assay method used in the various contradicting studies. While the standard Limulus amebocyte lysate (LAL) is reactive for ET and beta-glucan, a novel turbidimetric assay method enables separate determinations of ET and beta-glucan. Beagle dogs undergoing orthotopic liver transplantation were divided into two groups. In Group I (n = 6) the grafts were transplanted immediately and in Group II (n = 6) grafts were preserved for 48 h in University of Wisconsin (UW) solution. Animals received cyclosporine immunosuppression and were followed for 14 days. Daily measurements of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were performed. Samples for ET and beta-glucan measurement were collected serially and processed using the turbidimetric assay method. While no graft failure was seen in Group I, three of six Group II animals died from graft failure within 1 day after transplantation. Preservation and reperfusion injury was much more severe in the Group II grafts than in Group I grafts. While endotoxemia could not be detected, postoperative beta-glucan levels (undetectable pretransplant) were seen in both groups. Beta-glucan levels were much higher in Group II grafts than in Group I grafts, and correlated with the severity of liver damage. In conclusion, this study shows that beta-glucan, instead of ET, appears during the early posttransplant period. We believe that posttransplant elevation of beta-glucan is related to liver damage, especially endothelial damage by preservation and reperfusion

Light Induced Increase of Electron Diffusion Length in a p n Junction Type CH3NH3PbBr3 Perovskite Solar Cell

High band gap, high open circuit voltage solar cells with methylammonium lead tribromide MAPbBr3 perovskite absorbers are of interest for spectral splitting and photoelectrochemical applications, because of their good performance and ease of processing. The physical origin of high performance in these and similar perovskite based devices remains only partially understood. Using cross sectional electron beaminduced current EBIC measurements, we find an increase in carrier diffusion length in MAPbBr3 Cl based solar cells upon low intensity a few percent of 1 sun intensity blue laser illumination. Comparing dark and illuminated conditions, the minority carrier electron diffusion length increases about 3.5 times from Ln 100 50 nm to 360 22 nm. The EBIC cross section profile indicates a p amp; 8722;n structure between the n FTO TiO2 and p perovskite, rather than the p amp; 8722;i amp; 8722;n structure, reported for the iodide derivative. On the basis of the variation in space charge region width with varying bias, measured by EBIC and capacitance amp; 8722;voltage measurements, we estimate the net doping concentration in MAPbBr3 Cl to be 3 amp; 8722;6 1017 cm amp; 8722;

The time is right to introduce an independent commissioner

The authors of Home et al (2020) respond to the Letter to the Editor on the call for an independent anti-female genital mutilation commissioner in the U