BTLA mediates inhibition of human tumor-specific CD8+ T cells that can be partially reversed by vaccination

The function of antigen-specific CD8+ T cells, which may protect against both infectious and malignant diseases, can be impaired by ligation of their inhibitory receptors, which include CTL-associated protein 4 (CTLA-4) and programmed cell death 1 (PD-1). Recently, B and T lymphocyte attenuator (BTLA) was identified as a novel inhibitory receptor with structural and functional similarities to CTLA-4 and PD-1. BTLA triggering leads to decreased antimicrobial and autoimmune T cell responses in mice, but its functions in humans are largely unknown. Here we have demonstrated that as human viral antigen-specific CD8+ T cells differentiated from naive to effector cells, their surface expression of BTLA was gradually downregulated. In marked contrast, human melanoma tumor antigen-specific effector CD8+ T cells persistently expressed high levels of BTLA in vivo and remained susceptible to functional inhibition by its ligand herpes virus entry mediator (HVEM). Such persistence of BTLA expression was also found in tumor antigen-specific CD8+ T cells from melanoma patients with spontaneous antitumor immune responses and after conventional peptide vaccination. Remarkably, addition of CpG oligodeoxynucleotides to the vaccine formulation led to progressive downregulation of BTLA in vivo and consequent resistance to BTLA-HVEM-mediated inhibition. Thus, BTLA activation inhibits the function of human CD8+ cancer-specific T cells, and appropriate immunotherapy may partially overcome this inhibition.

Arsenic and selenium mobilisation from organic matter treated mine spoil with and without inorganic fertilisation

Organic matter amendments are applied to contaminated soil to provide a better habitat for re-vegetation and remediation, and olive mill waste compost (OMWC) has been described as a promising material for this aim. We report here the results of an incubation experiment carried out in flooded conditions to study its influence in As and metal solubility in a trace elements contaminated soil. NPK fertilisation and especially organic amendment application resulted in increased As, Se and Cu concentrations in pore water. Independent of the amendment, dimethylarsenic acid (DMA) was the most abundant As species in solution. The application of OMWC increased pore water dissolved organic-carbon (DOC) concentrations, which may explain the observed mobilisation of As, Cu and Se; phosphate added in NPK could also be in part responsible of the mobilisation caused in As. Therefore, the application of soil amendments in mine soils may be particularly problematic in flooded systems.

Using Factorial Surveys and Stated Choice Experiments to Investigate Discriminatory Attitudes and Preferences

Empirical research on discriminatory attitudes and behaviour grapples with the social undesirability of its object. In many studies using regular survey methods, estimates are biased, and the social context of discrimination is not taken into account. Several methods have been developed, especially to deal with the first problem. In this regard, the estimation of the ‘true value’ of discriminatory attitudes is at the centre of interest. However, methodological contributions focusing on the social context of attitude communication and discriminatory behaviour, as well as the correlation between both, are rare. We present two experimental methods which address those issues: factorial surveys and stated choice experiments. In a first study, the usefulness of factorial surveys is demonstrated with data on German anti-Semitism (N=279). We show that the rate of approval with anti-Semitic statements increases if (a) respondents are told that the majority of fellows agree with such statements, (b) the term “Jews” is replaced by the term “Israelis”, and (c) reference to the Holocaust is made. Apart from the main effects of these experimental factors, significant interaction effects regarding the political attitudes and social status of respondents are observed. In a second study, a stated choice experiment on the purchase of olive oil and tomatoes was conducted in Germany (N=440). We find that respondents prefer Italian and Dutch products (control treatment) compared to Israeli and Palestinian ones (discrimination treatments). There are no significant differences between preferences for a so called ‘Peace product’ (which is produced jointly by Israelis and Palestinians) and products from Italy as well as the Netherlands. Yet, taking discriminatory attitudes (anti-Semitic and anti-Arabic attitudes) into account, a strong correlation between those attitudes and stated behaviour (purchase of Israeli, Palestinian and jointly produced products) can be found. This adds support to the hypothesis that discriminatory attitudes hold behavioural consequences.