Impact of Donation Mode on the Proportion and Function of T Lymphocytes in the Liver

Background

Liver T-cells respond to the inflammatory insult generated during organ procurement and contribute to the injury following reperfusion. The mode of liver donation alters various metabolic and inflammatory pathways but the way it affects intrahepatic T-cells is still unclear.

Methods

We investigated the modifications occurring in the proportion and function of T-cells during liver procurement for transplantation. We isolated hepatic mononuclear cells (HMC) from liver perfusate of living donors (LD) and donors after brain death (DBD) or cardiac death (DCD) and assessed the frequency of T-cell subsets, their cytokine secretion profile and CD8 T-cell cytotoxicity function, responsiveness to a danger associated molecular pattern (High Mobility Group Box1, HMGB1) and association with donor and recipient clinical parameters and immediate graft outcome.

Results

We found that T-cells in healthy human livers were enriched in memory CD8 T-cells exhibiting a phenotype of non-circulating tissue-associated lymphocytes, functionally dominated by more cytotoxicity and IFN-γ-production in DBD donors, including upon activation by HMGB1 and correlating with peak of post-transplant AST. This liver-specific pattern of CD8 T-cell was prominent in DBD livers compared to DCD and LD livers suggesting that it was influenced by events surrounding brain death, prior to retrieval.

Conclusion

Mode of liver donation can affect liver T-cells with increased liver damage in DBD donors. These findings may be relevant in designing therapeutic strategies aimed at organ optimization prior to transplantation.     

Miscanthus sacchariflorus – biofuel parent or new weed?

The perennial grass triploid Miscanthus × giganteus is a promising renewable bioenergy feedstock in the United States and Europe. Originating from eastern Asia, this species is a sterile hybrid cross between M. sinensis and M. sacchariflorus. While research has begun to examine the impacts of M. sinensis and triploid M. × giganteus on the landscape, M. sacchariflorus has been largely overlooked in the peer‐reviewed literature. This review article discusses the origin, uses, distribution, and invasive potential of M. sacchariflorus. M. sacchariflorus is capable of producing high yields (10.7 t DM ha^?1 yr^?1), generally does not reproduce by seed, and can be challenging to establish due to poor cold tolerance, likely due to the limited germplasm used in evaluations. However, M. sacchariflorus has abundant and aggressively spreading rhizomes, which underscores its invasive risk. In the United States, it is listed as escaped from cultivation in at least eight states, primarily in the Midwest, although it is likely that not all populations have been reported. As such, it is essential to generate a comprehensive dataset of all known M. sacchariflorus populations and monitor any continued spread of this species.     

Gall Stones in Patients with Disorders of the Terminal Ileum and Disturbed Bile Salt Metabolism

In a combined historical and radiological survey gall stones were found in 23 out of 72 patients with disorders of the terminal ileum (31·9%). This is four to five times the expected incidence of cholelithiasis. In these patients the incidence of gall stones was not related to age, but did, however, increase with increased duration of the ileal disorder. Glycine/taurine conjugation ratios of bile salts in the bile were abnormally high in 10 out of 11 patients with ileal disorders. Both impaired bile salt recirculation and absorption of poorly soluble bacterially degraded bile salts are possible causes of cholelithiasis in these patients.     

Hemagglutinin Stalk-Based Universal Vaccine Constructs Protect against Group 2 Influenza A Viruses

Current influenza virus vaccines contain H1N1 (phylogenetic group 1 hemagglutinin), H3N2 (phylogenetic group 2 hemagglutinin), and influenza B virus components. These vaccines induce good protection against closely matched strains by predominantly eliciting antibodies against the membrane distal globular head domain of their respective viral hemagglutinins. This domain, however, undergoes rapid antigenic drift, allowing the virus to escape neutralizing antibody responses. The membrane proximal stalk domain of the hemagglutinin is much more conserved compared to the head domain. In recent years, a growing collection of antibodies that neutralize a broad range of influenza virus strains and subtypes by binding to this domain has been isolated. Here, we demonstrate that a vaccination strategy based on the stalk domain of the H3 hemagglutinin (group 2) induces in mice broadly neutralizing anti-stalk antibodies that are highly cross-reactive to heterologous H3, H10, H14, H15, and H7 (derived from the novel Chinese H7N9 virus) hemagglutinins. Furthermore, we demonstrate that these antibodies confer broad protection against influenza viruses expressing various group 2 hemagglutinins, including an H7 subtype. Through passive transfer experiments, we show that the protection is mediated mainly by neutralizing antibodies against the stalk domain. Our data suggest that, in mice, a vaccine strategy based on the hemagglutinin stalk domain can protect against viruses expressing divergent group 2 hemagglutinins.     

Structure and assembly of turnip crinkle virus. VI. Identification of coat protein binding sites on the RNA

Structural studies of turnip crinkle virus have been extended to include the identification of high-affinity coat protein binding sites on the RNA genome. Virus was dissociated at elevated pH and ionic strength, and a ribonucleoprotein complex (rp-complex) was isolated by chromatography on Sephacryl S-200. Genomic RNA fragments in the rp-complex, resistant to RNase A and RNase T1 digestion and associated with tightly bound coat protein subunits, were isolated using coat-protein-specific antibodies. The identity of the protected fragments was determined by direct RNA sequencing. These approaches allowed us to study the specific RNA-protein interactions in the rp-complex obtained from dissociated virus particles. The location of one protected fragment downstream from the amber terminator codon in the first and largest of the three viral open reading frames suggests that the coat protein may play a role in the regulation of the expression of the polymerase gene. We have also identified an additional cluster of T1-protected fragments in the region of the coat protein gene that may represent further high-affinity sites involved in assembly recognition.