TCR-αβ+ DN T cells (CD3+ TCR-αβ+ CD4− CD8− NK1.1− CD49b−) represent a minor heterogeneous population in healthy mice and humans. Both pro-inflammatory and regulatory capacities have been attributed to these cells which are expanded in several autoimmune diseases. Importantly, previous work indicates that self-reactive CD8+ T cells become DN after activation by self-antigens, suggesting that self-reactive T cells may exist within the DN T cell population. Here, we demonstrate that in unmanipulated mice, PD-1 expression identifies a subset of DN T cells that display activation-associated markers and a phenotype that strongly suggests they derive from self-reactive CD8+ cells. We show that the majority of the pro-inflammatory cytokines produced by DN T cells are generated by the PD-1+ subset. Finally, using a TCR-activation reporter mouse (Nur77-GFP), we confirm that PD-1+ DN T cells have engaged endogenous antigen in healthy mice during steady state conditions. In conclusion, we provide evidence that indicates that the PD-1+ fraction of DN T cells represents self-reactive cells.

Neopterin, a product of activated white blood cells, is a marker of nonspecific inflammation that can capture variation in immune investment or disease-related immune activity and can be collected noninvasively in urine. Mounting studies in wildlife point to lifetime patterns in neopterin related to immune development, aging, and certain diseases, but rarely are studies able to assess whether neopterin can capture multiple concurrent dimensions of health and disease in a single system. We assessed the relationship between urinary neopterin stored on filter paper and multiple metrics of health and disease in wild geladas (Theropithecus gelada), primates endemic to the Ethiopian highlands. We tested whether neopterin captures age-related variation in inflammation arising from developing immunity in infancy and chronic inflammation in old age, inflammation related to intramuscular tapeworm infection, helminth-induced anti-inflammatory immunomodulation, and perturbations in the gastrointestinal microbiome. We found that neopterin had a U-shaped relationship with age, no association with larval tapeworm infection, a negative relationship with metrics related to gastrointestinal helminth infection, and a negative relationship with microbial diversity. Together with growing research on neopterin and specific diseases, our results demonstrate that urinary neopterin can be a powerful tool for assessing multiple dimensions of health and disease in wildlife.

Background: Depression is prevalent across the spectrum of Chronic Kidney Disease and associated with poorer outcomes. There is limited evidence regarding the most effective interventions and care pathways for depression in Chronic Kidney Disease.Objectives: To investigate how depression is identified and managed in adults with Chronic Kidney Disease.Design: Scoping review.Methods: Systematic search of eight databases with pre-defined inclusion criteria.Data relevant to the identification and/or management of depression in adults with Chronic Kidney Disease were extracted.Results: Of 2147 articles identified, 860 were included. Depression was most identified using self-report screening tools (n = 716 studies, 85.3%), with versions of the Beck Depression Inventory (n = 283, 33.7%) being the most common. A total of 123 studies included data on the management of depression, with nonpharmacological interventions being more frequently studied (n = 55, 45%). Cognitive Behavioural Therapy (n = 15) was the most common nonpharmacological intervention, which was found to have a significant effect on depressive symptoms compared to controls (n = 10). However, how such approaches could be implemented as part of routine care was not clear. There was limited evidence for antidepressants use in people with Chronic Kidney Disease albeit in a limited number of studies.

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