Advances in the understanding of B-cell biology are anticipated to further broaden options and improve outcomes.”
“Background. Programmed death receptor-1 (PD-1) compromises cytomegalovirus (CMV)-specific T-cell responses and has been linked to CMV viremia after transplantation. An impaired functional and proliferative capacity of PD-1-positive CMV-specific T cells may be reversed by the antibody-mediated blockade of PD-1 signaling. However, knowledge is limited on changes in “”cytokinome”" expression profiles associated with reversal of functional exhaustion.
Methods. The “”cytokinome”" was analyzed by 27-plex Luminex technology
comparing renal transplant recipients with low (n = 5) and high (n = 5) PD-1 expression on CMV-specific T cells. The effect of blocking PD-1 by PD-ligand (PD-L) antibodies on restoration of cytokine expression was examined.
Results. CMV-specific cytokine CB-839 inhibitor release and proliferation was lower in patients with high PD-1 expression on CMV-specific T cells. Antibody-mediated blockade of PD-L in CMV-stimulated samples restored expression levels of interleukin (IL)-1 beta, IL-2,
IL-6, IL-9, IL-10, granulocyte colony-stimulating factor, interferon-gamma, macrophage inflammatory protein-1 alpha, and tumor necrosis factor-alpha. By contrast, no profound effect CH5183284 research buy was observed for controls or patients with low PD-1 expression, or in staphylococcal enterotoxin B-stimulated cells.
Conclusion. Taken together, this pilot LY2835219 manufacturer study provides evidence that a high PD-1 expression on CMV-specific T cells actively impairs proliferation and “”cytokinome”" responses in an antigen-specific manner. Importantly, blockade of PD-L restores CMV-specific T-cell proliferation and expression of a panel of different proinflammatory and/or type 1 cytokines, suggesting a common but as yet unknown regulatory principle. We conclude that PD-1 exhaustion is
reversible and potentially amenable to therapeutic ex vivo and possibly in vivo manipulation. However, detailed knowledge of the differential effects on the “”cytokinome”" will be necessary to increase the safety and the efficacy of such manipulations.”
“Objectives: We measured concentrations of lead (Pb), manganese (Mn), chromium (Cr), and copper (Cu) in umbilical cord whole blood and examined sources of environmental Pb exposures in a predominantly African-American population.
Methods: Between April and July 2006, we collected reproductive histories, questionnaires, and blood samples from 102 women, aged 16-45 years, who delivered at a Memphis, TN hospital.
Results: The prevalence of preeclampsia and low birth weight infancy in the study population was 11% and 10%, respectively. Twenty-eight percent of mothers reported living near a potential Pb-contaminated area, while 43% lived in a residence built before 1978. Geometric mean (GM) concentrations for umbilical cord blood in the study population were 1.3, 3.5, 9.0, and 52.