Molecular signatures distinguish human central memory from effector memory CD8 T cell subsets

Abstract Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naive central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that TCM have a gene expression and cytokine signaling signature that lies between that of naive and TEM or TEMRA cells, whereas TEM and TEMRA are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that TEM and TEMRA cells strongly express genes with known importance in CD8 T cell effector function. In contrast, TCM are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish TCM and TEM/TEMRA at the molecular level and are consistent with the concept that TCM represent memory stem cells.</jats:p

Human naive CD8 T cells down-regulate expression of the WNT pathway transcription factors lymphoid enhancer binding factor 1 and transcription factor 7 (T cell factor-1) following antigen encounter in vitro and in vivo

Abstract The transcription factors lymphoid enhancer binding factor 1 (LEF1) and transcription factor 7 (TCF7) (T cell factor-1 (TCF-1)) are downstream effectors of the WNT signaling pathway, which is a critical regulator of T cell development in the thymus. In this study, we show that LEF1 and TCF7 (TCF-1) are not only expressed in thymocytes, but also in mature T cells. Our data demonstrate that Ag encounter in vivo and engagement of the TCR or IL-15 receptor in vitro leads to the down-regulation of LEF1 and TCF7 (TCF-1) expression in human naive CD8 T cells. We further show that resting T cells preferentially express inhibitory LEF1 and TCF7 (TCF-1) isoforms and that T cell activation changes the isoform balance in favor of stimulatory TCF7 (TCF-1) isoforms. Altogether, our study suggests that proteins involved in the WNT signaling pathway not only regulate T cell development, but also peripheral T cell differentiation.</jats:p

In an interconnected world: Joint research priorities for the environment, agriculture and infectious disease

In 2008 the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases (TDR) commissioned ten think-tanks to work on disease-specific and thematic reference groups to identify top research priorities that would advance the research agenda on infectious diseases of poverty, thus contributing to improvements in human health. The first of the thematic reference group reports - on environment, agriculture and infectious diseases of poverty - was recently released. In this article we review, from an insider perspective, the strengths and weaknesses of this thematic reference group report and highlight key messages for policy-makers, funders and researchers

Waiting for the wave, but missing the tide: Case studies of climate-related (im)mobility and health

Climate change amplifies health risks, including through the health impacts of climate-related displacement. Yet diverse mobility responses in a warming world can also provide a pathway for climate change adaptation. This article examines the connections between climatic and environmental change, human mobility and health. It presents case studies across three countries: Fiji, Bangladesh, and Burkina Faso. All case studies used qualitative methods, including semi-structured interviews, storytelling, and group discussions. The Fiji case study focuses on relocation of a coastal village exposed to erosion, flooding and saltwater intrusion; it highlights self-reported health risks and opportunities following relocation. The Bangladesh case study includes seven sites that variously experience flooding, cyclones and riverbank erosion; while residents use migration and mobility as a coping strategy, there are associated health risks, particularly for those who feel trapped in new sites of residence. The case study from a village in Burkina Faso examines seasonal labour migration to the Ivory Coast and Mali during times of drought and reduced agricultural productivity, and discusses health risks for men who migrate and for women who remain in sending communities. These case studies illustrate that there is no consistent figure that represents a 'climate migrant', ‘climate refugee’, or ‘trapped’ person. Accordingly, we argue that where planetary health looks to highlight ‘waves’ of climate displacement, it may miss the ‘tide’ of slower onset climatic changes and smaller-scale and diverse forms of (im)mobility. However, even where climate-related mobility is broadly adaptive - e.g. providing opportunities for livelihood diversification, or migration away from environmental risks - there can be health risks and opportunities that are shaped by socio-political contexts, access to healthcare, altered food sources, and living and working conditions. Responsive solutions are required to protect and promote the health of mobile populations in a warming world

Early motherhood: A qualitative study exploring the experiences of African Australian teenage mothers in greater Melbourne, Australia

BACKGROUND: Motherhood is a significant and important aspect of life for many women around the globe. For women in communities where motherhood is highly desired, motherhood is considered crucial to the woman's identity. Teenage motherhood, occurring at a critical developmental stage of teenagers' lives, has been identified as having adverse social and health consequences. This research aimed to solicit the lived experiences of African Australian young refugee women who have experienced early motherhood in Australia. METHODS: This qualitative research used in-depth interviews. The research methods and analysis were informed by intersectionality theory, phenomenology and a cultural competency framework. Sixteen African born refugee young women who had experienced teenage pregnancy and early motherhood in Greater Melbourne, Australia took part in this research. Interviews were audio recorded, transcribed and data analysed using thematic content analysis. Ethics approval for this research was granted by Victoria University Human Research Ethics committee. RESULTS: Motherhood brings increased responsibilities, social recognition, and a sense of purpose for young mothers. Despite the positive aspects of motherhood, participants faced challenges that affected their lives. Most often, the challenges included coping with increased responsibilities following the birth of the baby, managing the competing demands of schooling, work and taking care of a baby in a site of settlement. The young mothers indicated they received good support from their mothers, siblings and close friends, but rarely from the father of their baby and the wider community. Participants felt that teenage mothers are frowned upon by their wider ethnic communities, which left them with feelings of shame and embarrassment, despite the personal perceived benefits of achieving motherhood. CONCLUSIONS: We propose that service providers and policy makers support the role of the young mothers' own mother, sisters, their grandmothers and aunts following early motherhood. Such support from significant females will help facilitate young mothers' re-engagement with education, work and other aspects of life. For young migrant mothers, this is particularly important in order to facilitate settlement in a new country and reduce the risk of subsequent mistimed pregnancies. Service providers need to expand their knowledge and awareness of the specific needs of refugee teen mothers living in 'new settings'