Simultaneous expression of CD4 and CD8 antigens by a substantial proportion of resting porcine T lymphocytes

The existence of four subpopulations in resting porcine T lymphocytes is documented. In addition to the two known subpopulations which are typified by a mutually exclusive expression of either the CD8 or the CD4 differentiation antigen, CD4-CD8+ and CD4+CD8- T lymphocytes, respectively, two unusual subpopulations were prominent not only in peripheral blood, but also in lymphoid tissues: CD4-CD8- T lymphocytes expressing neither of these antigens and CD4+CD8+ T lymphocytes coexpressing both antigens. While CD4+CD8+ lymphoblasts have been found also in other species, resting T lymphocytes with that phenotype are without precedent among all species analyzed to date. This unique composition of the porcine T lymphocyte population has to be taken into consideration when the swine is used as a large animal model in experimental medicine

Speaking out about gender imbalance in invited speakers improves diversity.

Omissions of qualified women scientists from major meeting programs continue to occur despite a surge in articles indicating persistent gender-discriminatory practices in hiring and promotion, and calls for gender balance in conference organizing committees

Emerging immunopharmacological targets in multiple sclerosis.

Inflammatory demyelination of the central nervous system (CNS) is the hallmark of multiple sclerosis (MS), a chronic debilitating disease that affects more than 2.5 million individuals worldwide. It has been widely accepted, although not proven, that the major pathogenic mechanism of MS involves myelin-reactive T cell activation in the periphery and migration into the CNS, which subsequently triggers an inflammatory cascade that leads to demyelination and axonal damage. Virtually all MS medications now in use target the immune system and prevent tissue damage by modulating neuroinflammatory processes. Although current therapies such as commonly prescribed disease-modifying medications decrease the relapse rate in relapsing-remitting MS (RRMS), the prevention of long-term accumulation of deficits remains a challenge. Medications used for progressive forms of MS also have limited efficacy. The need for therapies that are effective against disease progression continues to drive the search for novel pharmacological targets. In recent years, due to a better understanding of MS immunopathogenesis, new approaches have been introduced that more specifically target autoreactive immune cells and their products, thus increasing specificity and efficacy, while reducing potential side effects such as global immunosuppression. In this review we describe several immunopharmacological targets that are currently being explored for MS therapy

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Intravenous Sodium Thiosulphate for Calciphylaxis of Chronic Kidney Disease:A Systematic Review and Meta-analysis

Importance: Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label therapeutic in calciphylaxis, but there is a lack of clinical trials and studies that demonstrate its effect compared with those without STS treatment. Objective: To perform a meta-analysis of the cohort studies that provided data comparing outcomes among patients with calciphylaxis treated with and without intravenous STS. Data Sources: PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using relevant terms and synonyms including sodium thiosulphate and calci∗ without language restriction. Study Selection: The initial search was for cohort studies published before August 31, 2021, that included adult patients diagnosed with CKD experiencing calciphylaxis and could provide a comparison between patients treated with and without intravenous STS. Studies were excluded if they reported outcomes only from nonintravenous administration of STS or if the outcomes for CKD patients were not provided. Data Extraction and Synthesis: Random-effects models were performed. The Egger test was used to measure publication bias. Heterogeneity was assessed using the I2test. Main Outcomes and Measures: Skin lesion improvement and survival, synthesized as ratio data by a random-effects empirical Bayes model. Results: Among the 5601 publications retrieved from the targeted databases, 19 retrospective cohort studies including 422 patients (mean age, 57 years; 37.3% male) met the eligibility criteria. No difference was observed in skin lesion improvement (12 studies with 110 patients; risk ratio, 1.23; 95% CI, 0.85-1.78) between the STS and the comparator groups. No difference was noted for the risk of death (15 studies with 158 patients; risk ratio, 0.88; 95% CI, 0.70-1.10) and overall survival using time-to-event data (3 studies with 269 participants; hazard ratio, 0.82; 95% CI, 0.57-1.18). In meta-regression, lesion improvement associated with STS negatively correlated with publication year, implying that recent studies are more likely to report a null association compared with past studies (coefficient = -0.14; P =.008). Conclusions and Relevance: Intravenous STS was not associated with skin lesion improvement or survival benefit in patients with CKD experiencing calciphylaxis. Future investigations are warranted to examine the efficacy and safety of therapies for patients with calciphylaxis.</p

Register shifting of an insulin peptide–MHC complex allows diabetogenic T cells to escape thymic deletion

A single amino acid shift in TCR recognition of self peptide–MHC determines whether potentially diabetogenic CD4 T cells will be purged in the thymus or have the opportunity to undergo activation in the islets of Langerhans of mice