Several subsets of αβ regulatory T cells (Tregs) have been described and studied intensively, but the potential regulatory role of γδ T cells remains largely unclear. Lymphocytes expressing γδ TCR are involved in both innate and adaptive immune responses, and their major adult human peripheral blood subset (Vγ9Vδ2) displays a broad reactivity against microbial agents and tumors. In this study we report that γδ T lymphocytes with regulatory functions (Vδ2 Tregs) are induced in vitro in the presence of specific Ag stimulation and cytokines (TGF-β1 and IL-15). These cells express FOXP3 and, similarly as αβ Tregs, suppress the proliferation of anti-CD3/anti-CD28 stimulated-PBMC. Phenotypic and functional analyses of Vδ2 Tregs will very likely improve our understanding about the role of γδ T cells in the pathogenesis of autoimmune, infectious, and neoplastic diseases.
The pathogenesis of sepsis is characterized by the inability of the host to regulate the inflammatory response, and as a consequence, dysregulated inflammatory processes induce organ dysfunctions and death. Altered transglutaminase type II (TG2) expression is associated with the development of many inflammatory diseases. Therefore, in this study, we questioned whether TG2 could also contribute to the pathological inflammatory dysregulation occurring in septic shock in vivo. To this aim, we used as an experimental model the TG2 knockout mice, in which the process of septic shock was elicited by treatment with LPS. Interestingly, our results demonstrated that TG2 ablation leads to partial resistance to experimental sepsis. The increased survival of TG2−/− mice was reflected in a drastic reduction of organ injury, highlighted by a limited infiltration of neutrophils in kidney and peritoneum and by a better homeostasis of the proinflammatory mediators as well as mitochondrial function. We also showed that in wild-type mice, the TG2 expression is increased during endotoxemia and, being directly involved in the mechanisms of NF-κB activation, it may cause a continuous activation cycle in the inflammatory process, thus contributing to development of sepsis pathogenesis. We propose that the inhibition of TG2 could represent a novel approach in the treatment of inflammatory processes associated with sepsis.
The COVID-19 pandemic has changed individuals' lifestyles to a great extent, particularly in Italy. Although many concerns about it have been highlighted, its impact on children and adolescents has scarcely been examined. The purpose of this study was to explore behavioral consequences and coping strategies related to the pandemic among families in Italy, by focusing on developmental ages from the caregivers' perspective, 3 weeks into quarantine. An exploratory cross-sectional online survey was conducted over 14 days. Google Forms was employed to conduct the survey. Demographic variables and pre-existing Psychological Weaknesses (PsW) were asked. Adults' sleep difficulties (SleepScore) and coping strategies during quarantine were assessed. Behavioral changes related to quarantine of both subjects completing the form (COVIDStress) and their children (when present) were questioned. Of the 6,871 respondents, we selected 6,800 valid questionnaires; 3,245 declared children aged under 18 years of age (caregivers). PsWs were recognizable in 64.9% among non-caregivers and in 61.5% of caregivers, with a mean PsW score of 1.42 ± 1.26 and 1.30 ± 1.25 over 3 points, respectively. The 95.5% of the non-caregivers and the 96.5% of caregivers presented behavioral changes with a mean COVIDStress of 3.85 ± 1.82 and 4.09 ± 1.79 over 8, respectively (p<0.001). Sleep difficulties were present in the 61.6% of the non-caregivers and in the 64.4% of the caregivers (p < 0.001), who showed higher SleepScores (2.41 ± 1.26 against 2.57 ± 1.38 points over 6, p < 0.001). COVIDStress (and SleepScore) strongly correlated with PsW (p < 0.001). Caregivers observed behavioral changes in their children in the 64.3% of the <6 years old and in 72.5% of 6–18 years old. Caregivers' discomfort related to quarantine (COVIDStress, SleepScore) was strongly associated to behavioral changes in both age groups of <6 and 6–18 (p < 0.001). Presence of caregivers' coping strategies was less associated to behavioral changes in the <6 sample (p = 0.001) but not in the 6–18 (p = 0.06). The COVID-19 pandemic has adversely impacted families in Italy with regard to behavioral changes, especially in high-risk categories with PsWs and caregivers, especially the ones with children aged <6 years. While coping strategies functioned as protective factors, a wide array of stress symptoms had implications for children's and adolescents' behaviors. It is recommended that public children welfare strategies be implemented, especially for higher-psychosocial-risk categories.
Vero cells transfected with either neo- or bcl-2-plasmid were infected with SARS-CoV at a high multiplicity of infection. Apoptosis appeared after the onset of CPE and completion of virus replication, and could be prevented by Bcl-2 expression. Apoptosis is likely mediated by the mitochondrial pathway, as demonstrated by its inhibition using Bcl-2, and by the activation of the caspase cascade, resulting in PARP cleavage. Prevention of apoptosis did not affect susceptibility to infection, kinetics and extent of viral replication and release, thus implying that apoptosis is not involved in facilitating release and/or dissemination of SARS-CoV in Vero cells.
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