Dealing With Wild Pig Depredation In California: The Strategic Plan

The Wild Pig Management Plan is required by Fish and Game Code Section 4651. It is intended to be a strategic plan for dealing with wild pigs for the five-year period 1995-2000. The plan is a dynamic document that will be reviewed and updated at least every five years. As prescribed by law, the plan contains information related to the status and trend of wild pig populations, and describes management units established by the Department to address regional needs and opportunities. Those needs include alleviating damage to property, protecting sensitive natural resources, and providing recreational hunting where feasible. Opportunities include using the demand for recreational hunting of wild pigs as a practical and cost-effective means of controlling wild pigs and their impact on property and natural resources. In addition, there are opportunities for cooperation between public agencies, conservation organizations, and private landowners that use incentives to manage wild pigs in conjunction with primary land use objectives. The plan invites participation from the public and incorporates the results of surveys and applied research to achieve stated objectives. The plan has seven objectives as follows: 1) Study the distribution and density of wild pigs in California. 2) Reduce wild pig depredation on private land. 3) Increase hunting opportunities. 4) Determine the impact of wild pigs on native communities and agricultural areas. 5) Provide public information. 6) Monitor disease, both endemic and exotic, in the wild pig population. 7) Investigate the economic impact of wild pigs. This paper will only concentrate on that aspect of the plan that deals with reducing wild pig depredation on private land

Tissue-resident memory T cells orchestrate tumour-immune equilibrium

The immune system can prevent tumour development by engaging in a process termed cancer immunosurveillance, during which immune cells such as T cells restrict tumour growth either by completely eradicating cancer cells in a process of ‘elimination’ or by suppressing cancer cell outgrowth by establishing a state of tumour-immune ‘equilibrium’. Most cancers develop within epithelial layers of tissues but circulating T cells are largely excluded from these epithelial tissue compartments in the absence of infection or overt inflammation. In contrast, CD8+ tissue-resident memory T (TRM) cells reside permanently within epithelial layers of peripheral tissues without recirculating in blood. Accumulating evidence suggests that TRM cells are found in diverse human solid cancers where they correlate with improved prognosis and can protect against tumour challenge in mice. However, the mechanisms through which these cells mediate cancer protection are poorly understood. In our recent study (Park SL et al, Nature 565(7739), 2019) we developed a melanoma model that allowed us to identify a critical role for TRM cells in the establishment and maintenance of tumour-immune equilibrium in skin. Our findings provide insight into the immune cell populations important for maintaining long-term tumour dormancy in peripheral tissues and imply that targeting TRM cells may serve as a novel cancer treatment strategy

Identifying the optimal donor for natural killer cell adoptive therapy to treat paediatric B- and T-cell acute lymphoblastic leukaemia.

Objectives: Natural killer (NK) cells are an attractive source of cells for an 'off the shelf' cellular therapy because of their innate capacity to target malignant cells, and ability to be transferred between donors and patients. However, since not all NK cells are equally effective at targeting cancer, selecting the right donor for cellular therapy is critical for the success of the treatment. Recently, cellular therapies utilising NK cells from cytomegalovirus (CMV)-seropositive donors have been explored. However, whether these NK cells are the best source to treat paediatric acute lymphoblastic leukaemia (ALL) remains unclear. Methods: Using a panel of patient-derived paediatric B- and T-ALL, we assessed the ability of NK cells from 49 healthy donors to mount an effective functional response against these two major subtypes of ALL. Results: From this cohort, we have identified a pool of donors with superior activity against multiple ALL cells. While these donors were more likely to be CMV+, we identified multiple CMVneg donors within this group. Furthermore, NK cells from these donors recognised B- and T-ALL through different activating receptors. Dividing functional NK cells into 29 unique subsets, we observed that within each individual the same NK cell subsets dominated across all ALL cells. Intriguingly, this occurred despite the ALL cells in our panel expressing different combinations of NK cell ligands. Finally, we can demonstrate that cellular therapy products derived from these superior donors significantly delayed leukaemia progression in preclinical models of ALL. Conclusions: We have identified a pool of superior donors that are effective against a range of ALL cells, representing a potential pool of donors that can be used as an adoptive NK cell therapy to treat paediatric ALL

Escherichia coli O157:H7 in Feral Swine near Spinach Fields and Cattle, Central California Coast1

We investigated involvement of feral swine in contamination of agricultural fields and surface waterways with Escherichia coli O157:H7 after a nationwide outbreak traced to bagged spinach from California. Isolates from feral swine, cattle, surface water, sediment, and soil at 1 ranch were matched to the outbreak strain

CCR6 is expressed on an IL-10–producing, autoreactive memory T cell population with context-dependent regulatory function

Interleukin (IL)-10 produced by regulatory T cell subsets is important for the prevention of autoimmunity and immunopathology, but little is known about the phenotype and function of IL-10–producing memory T cells. Human CD4+CCR6+ memory T cells contained comparable numbers of IL-17– and IL-10–producing cells, and CCR6 was induced under both Th17-promoting conditions and upon tolerogenic T cell priming with transforming growth factor (TGF)–β. In normal human spleens, the majority of CCR6+ memory T cells were in the close vicinity of CCR6+ myeloid dendritic cells (mDCs), and strikingly, some of them were secreting IL-10 in situ. Furthermore, CCR6+ memory T cells produced suppressive IL-10 but not IL-2 upon stimulation with autologous immature mDCs ex vivo, and secreted IL-10 efficiently in response to suboptimal T cell receptor (TCR) stimulation with anti-CD3 antibodies. However, optimal TCR stimulation of CCR6+ T cells induced expression of IL-2, interferon-γ, CCL20, and CD40L, and autoreactive CCR6+ T cell lines responded to various recall antigens. Notably, we isolated autoreactive CCR6+ T cell clones with context-dependent behavior that produced IL-10 with autologous mDCs alone, but that secreted IL-2 and proliferated upon stimulation with tetanus toxoid. We propose the novel concept that a population of memory T cells, which is fully equipped to participate in secondary immune responses upon recognition of a relevant recall antigen, contributes to the maintenance of tolerance under steady-state conditions

Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection

Although mucosal surfaces represent the main portal of entry for pathogens, the mechanism of antigen presentation by dendritic cells (DCs) that patrol various mucosal tissues remains unclear. Instead, much effort has focused on the understanding of initiation of immune responses generated against antigens delivered by injection. We examined the contributions of migratory versus lymph node–resident DC populations in antigen presentation to CD4 and CD8 T cells after needle injection, epicutaneous infection, or vaginal mucosal herpes simplex virus (HSV) 1 infection. We show that upon needle injection, HSV-1 became lymph-borne and was rapidly presented by lymph node–resident DCs to CD4 and CD8 T cells. In contrast, after vaginal HSV-1 infection, antigens were largely presented by tissue-derived migrant DCs with delayed kinetics. In addition, migrant DCs made more frequent contact with HSV-specific T cells after vaginal infection compared with epicutaneous infection. Thus, both migrant and resident DCs play an important role in priming CD8 and CD4 T cell responses, and their relative importance depends on the mode of infection in vivo

IL-2 Mediates CD4+ T Cell Help in the Breakdown of Memory-Like CD8+ T Cell Tolerance under Lymphopenic Conditions

Background: Lymphopenia results in the proliferation and differentiation of naïve T cells into memory-like cells in the apparent absence of antigenic stimulation. This response, at least in part due to a greater availability of cytokines, is thought to promote anti-self responses. Although potentially autoreactive memory-like CD8 + T cells generated in a lymphopenic environment are subject to the mechanisms of peripheral tolerance, they can induce autoimmunity in the presence of antigen-specific memory-like CD4 + T helper cells. Methodology/Principal Findings: Here, we studied the mechanisms underlying CD4 help under lymphopenic conditions in transgenic mice expressing a model antigen in the beta cells of the pancreas. Surprisingly, we found that the self-reactivity mediated by the cooperation of memory-like CD8 + and CD4 + T cells was not abrogated by CD40L blockade. In contrast, treatment with anti-IL-2 antibodies inhibited the onset of autoimmunity. IL-2 neutralization prevented the CD4-mediated differentiation of memory-like CD8 + T cells into pathogenic effectors in response to self-antigen cross-presentation. Furthermore, in the absence of helper cells, induction of IL-2 signaling by an IL-2 immune complex was sufficient to promote memory-like CD8 + T cell self-reactivity. Conclusions/Significance: IL-2 mediates the cooperation of memory-like CD4 + and CD8 + T cells in the breakdown of crosstolerance, resulting in effector cytotoxic T lymphocyte differentiation and the induction of autoimmune disease