A Collaborative Approach to Systematic Marine Protected Area Network Planning in British Columbia

In British Columbia, legislated responsibilities for the protection of marine values are a shared responsibility between federal and provincial governments. Traditionally, the governments of Canada and B.C. have established marine protected areas (MPAs) independently, on an ad-hoc basis, and often in response to single species or habitat specific conservation issues. This is challenging because dual designation may be required to meet MPA objectives, and ad hoc approaches may lead to gaps in biophysical representation and greater uncertainty for marine stakeholders. Recognizing the need to partner together and move towards more systematic marine conservation planning, the governments of Canada and B.C. have completed a strategy for the design of a network of MPAs on the Pacific Coast. The strategy proposes a clear vision, identifies priority goals and objectives, and recommends a set of general operating and network design principles to guide development and implementation of a coast-wide network of MPAs. Identifying gaps in biophysical representation is a preliminary step towards future implementation. Initial GIS analyses suggest gaps in biophysical representation in existing MPAs, reinforcing the need for a more collaborative systematic approach to MPA network planning in BC. This presentation will describe how governments will work collaboratively to design an effective network of MPAs through existing integrated marine spatial planning processes

ADAM17-dependent proteolysis of L-selectin promotes early clonal expansion of cytotoxic T cells

L-selectin on T-cells is best known as an adhesion molecule that supports recruitment of blood-borne naïve and central memory cells into lymph nodes. Proteolytic shedding of the ectodomain is thought to redirect activated T-cells from lymph nodes to sites of infection. However, we have shown that activated T-cells re-express L-selectin before lymph node egress and use L-selectin to locate to virus-infected tissues. Therefore, we considered other roles for L-selectin proteolysis during T cell activation. In this study, we used T cells expressing cleavable or non-cleavable L-selectin and determined the impact of L-selectin proteolysis on T cell activation in virus-infected mice. We confirm an essential and non-redundant role for ADAM17 in TCR-induced proteolysis of L-selectin in mouse and human T cells and show that L-selectin cleavage does not regulate T cell activation measured by CD69 or TCR internalisation. Following virus infection of mice, L-selectin proteolysis promoted early clonal expansion of cytotoxic T cells resulting in an 8-fold increase over T cells unable to cleave L-selectin. T cells unable to cleave L-selectin showed delayed proliferation in vitro which correlated with lower CD25 expression. Based on these results, we propose that ADAM17-dependent proteolysis of L-selectin should be considered a regulator of T-cell activation at sites of immune activity

T cell phenotypes in COVID-19 - a living review

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation

The role and uses of antibodies in COVID-19 infections: a living review

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity

The superantigens SpeC and TSST-1 specifically activate TRBV12-3/12-4+ memory T cells

In peripheral blood mononuclear cells from healthy human donors, the superantigens SpeC and TSST-1 are shown to specifically activate TRBV12-3/12-4+ memory T cells

The superantigens SpeC and TSST-1 specifically activate TRBV12-3/12-4+ memory T cells

Severe bacterial or viral infections can induce a state of immune hyperactivation that can culminate in a potentially lethal cytokine storm. The classic example is toxic shock syndrome, a life-threatening complication of Staphylococcus aureus or Streptococcus pyogenes infection, which is driven by potent toxins known as superantigens (SAgs). SAgs are thought to promote immune evasion via the promiscuous activation of T cells, which subsequently become hyporesponsive, and act by cross-linking major histocompatibility complex class II molecules on antigen-presenting cells to particular β-chain variable (TRBV) regions of αβ T cell receptors (TCRs). Although some of these interactions have been defined previously, our knowledge of SAg-responsive TRBV regions is incomplete. In this study, we found that CD4+ and CD8+ T cells expressing TRBV12-3/12-4+ TCRs were highly responsive to streptococcal pyrogenic exotoxin C (SpeC) and toxic shock syndrome toxin-1 (TSST-1). In particular, SpeC and TSST-1 specifically induced effector cytokine production and the upregulation of multiple coinhibitory receptors among TRBV12-3/12-4+ CD4+ and CD8+ memory T cells, and importantly, these biological responses were dependent on human leukocyte antigen (HLA)-DR. Collectively, these data provided evidence of functionally determinative and therapeutically relevant interactions between SpeC and TSST-1 and CD4+ and CD8+ memory T cells expressing TRBV12-3/12-4+ TCRs, mediated via HLA-DR

Identifying priority areas for marine conservation in British Columbia: a collaborative approach

Implementation of marine conservation measures has been slow in British Columbia, providing the motivation\ud for initiating the British Columbia Marine Conservation Analysis (BCMCA) project. The purpose of the\ud BCMCA project is to collaboratively identify areas of high conservation interest for the marine waters of\ud British Columbia. The project team is comprised of representatives from academia, First Nations organizations,\ud non-profit environmental groups, federal and provincial government agencies, and user groups. The BCMCA\ud project is developing two products: 1) an atlas of known ecological and human use values; and 2) a series of\ud Marxan spatial analyses. The atlas will map ecological data, human use data, areas where data are lacking,\ud and a combination of areas of ecological value and more intensive human use. The Marxan spatial analyses\ud will iteratively identify: 1) areas with high conservation value based on ecological data only; 2) areas of high\ud conservation value that minimize overlap with areas important to human use; and 3) areas of high conservation\ud value that incorporate additional marine reserve design considerations. To guide and inform the analysis, we\ud held five ecological expert workshops focused on various ecosystem components, are engaging user groups,\ud and have a workshop planned to refine analysis methods. The ecological workshops drew on the knowledge and\ud expertise of resource managers, the conservation community, academics and First Nations, to help assemble and\ud use the best available data – biological, ecological and oceanographic – in developing sound, defensible analysis\ud methods and products. Results of the BCMCA project are intended to advance marine planning initiatives in\ud British Columbia by collaboratively and iteratively identifying potential areas of high conservation value