Natural killer (NK) cells from killers to regulators: Distinct features between peripheral blood and decidual NK cells

Natural killer (NK) cells are a key component of innate immunity, particularly crucial during the early phase of immune responses against certain viruses, parasites, and microbial pathogens. The role of NK cell during pregnancy has been vividly discussed over the past years and it is now becoming increasingly clear that NK cells control pregnancy maintenance at several levels. In normal pregnancy, it appears that they provide benefit by properly secreting cytokines, chemokines and angiogenic factors rather than functioning as cytotoxic effector cells. However, as they are endowed with all the cytolytic weapons, they promptly become capable of attacking fetal and maternal tissues during infection and inflammation. © 2007 The Authors Journal compilation 2007 Blackwell Munksgaard

Histone Deacetylase Inhibitors Impair the Elimination of HIV-Infected Cells by Cytotoxic T-Lymphocytes

Resting memory CD4+ T-cells harboring latent HIV proviruses represent a critical barrier to viral eradication. Histone deacetylase inhibitors (HDACis), such as suberanilohydroxamic acid (SAHA), romidepsin, and panobinostat have been shown to induce HIV expression in these resting cells. Recently, it has been demonstrated that the low levels of viral gene expression induced by a candidate HDACi may be insufficient to cause the death of infected cells by viral cytopathic effects, necessitating their elimination by immune effectors, such as cytotoxic T-lymphocytes (CTL). Here, we study the impact of three HDACis in clinical development on T-cell effector functions. We report two modes of HDACi-induced functional impairment: i) the rapid suppression of cytokine production from viable T-cells induced by all three HDACis ii) the selective death of activated T-cells occurring at later time-points following transient exposures to romidepsin or, to a lesser extent, panobinostat. As a net result of these factors, HDACis impaired CTL-mediated IFN-γ production, as well as the elimination of HIV-infected or peptide-pulsed target cells, both in liquid culture and in collagen matrices. Romidepsin exerted greater inhibition of antiviral function than SAHA or panobinostat over the dose ranges tested. These data suggest that treatment with HDACis to mobilize the latent reservoir could have unintended negative impacts on the effector functions of CTL. This could influence the effectiveness of HDACi-based eradication strategies, by impairing elimination of infected cells, and is a critical consideration for trials where therapeutic interruptions are being contemplated, given the importance of CTL in containing rebound viremia

Vertical schooling and learning transformations in curriculum research:points and counterpoints in outdoor education and sustainability

Urbanisation, environmental degradation, and lack of green spaces in dense metropolitan environments raises critical considerations for curriculum research. Urban densification has led to the prominence of high-rise architecture across city skylines and similar trends are underway in education where ‘vertical schooling’ (VS) is making its debut in Australia (Bleby 2016; Edwards 2017; The Urban Developer 2018). The issues discussed in this article relate to an impending future urban landscape of VS with limited space for direct contact and access to nature. Firstly, the prominence of VS within the national context is discussed, identifying critical questions relating to its potential impact on students’ access to, understandings of, and relationships with nature. Secondly, an overview of the benefits of nature and outdoor learning is presented and followed by an examination of curriculum links that support education for sustainability and place-based outdoor learning. Lastly, the new spatialities of VS are problematised, specifically in relation to the separation of schooling from community. The points and counterpoints highlight considerations regarding physical design and architecture on environmental and social sustainability, serving as a call for curriculum researchers to explore new ways of looking at nature in VS, and innovative approaches to making sense of the different meanings that become attached to such an idea