Dissecting the complexity of the memory T cell response

Memory immune responses are classically attributed to the reactivation of long-lived, antigen-specific T lymphocytes that persist in a quiescent state. Determining mechanisms for the generation of memory T cells and dissecting the functional nature of the memory T cell pool has been encumbered by an inability to distinguish recently activated effector T cells from memory T cells. We have established new activation and biochemical criteria that distinguish effector and memory T cells and have applied these criteria to follow memory generation from activated cells in vivo. We found that the resultant memory T cell pool is heterogeneous and consists of effector-like and resting memory-like subsets that differ in expression of the homing receptor, CD62L. We discuss these findings in the context of memory T cell heterogeneity identified in human and mouse systems. These results suggest that more than one type of previously activated T cell can mediate recall or memory immune responses and that elucidating the fundamental phenotypic and functional features of memory T cell subsets is therefore critical to deciphering the complex nature of the memory immune response.     

Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of thefirst phase I clinical trial

BACKGROUND: DC derived-exosomes are nanomeric vesicles harboring functional MHC/peptide complexes capable of promoting T cell immune responses and tumor rejection. Here we report the feasability and safety of the first Phase I clinical trial using autologous exosomes pulsed with MAGE 3 peptides for the immunization of stage III/IV melanoma patients. Secondary endpoints were the monitoring of T cell responses and the clinical outcome. PATIENTS AND METHODS: Exosomes were purified from day 7 autologous monocyte derived-DC cultures. Fifteen patients fullfilling the inclusion criteria (stage IIIB and IV, HLA-A1+, or -B35+ and HLA-DPO4+ leukocyte phenotype, tumor expressing MAGE3 antigen) were enrolled from 2000 to 2002 and received four exosome vaccinations. Two dose levels of either MHC class II molecules (0.13 versus 0.40 x 1014 molecules) or peptides (10 versus 100 mug/ml) were tested. Evaluations were performed before and 2 weeks after immunization. A continuation treatment was performed in 4 cases of non progression. RESULTS: The GMP process allowed to harvest about 5 x 1014 exosomal MHC class II molecules allowing inclusion of all 15 patients. There was no grade II toxicity and the maximal tolerated dose was not achieved. One patient exhibited a partial response according to the RECIST criteria. This HLA-B35+/A2+ patient vaccinated with A1/B35 defined CTL epitopes developed halo of depigmentation around naevi, a MART1-specific HLA-A2 restricted T cell response in the tumor bed associated with progressive loss of HLA-A2 and HLA-BC molecules on tumor cells during therapy with exosomes. In addition, one minor, two stable and one mixed responses were observed in skin and lymph node sites. MAGE3 specific CD4+ and CD8+ T cell responses could not be detected in peripheral blood. CONCLUSION: The first exosome Phase I trial highlighted the feasibility of large scale exosome production and the safety of exosome administration.     

Effect of 940 nm laser diode irradiation prior to bonding procedure on postoperative sensitivity following class II composite restorations: a split-mouth randomized clinical trial

The aim of this study was to evaluate the effect of 940 nm laser diode on class II composite cavities prior to bonding and restoration process on the postoperative sensitivity (POS). Thirty patients with two bilateral premolars with mesio or disto-occlusal carious lesions were evaluated. In each patient, the teeth were randomly divided into the control and laser groups. After cavity preparation and isolation and before the bonding process, the laser group was subjected to 940 nm irradiation (Epic 10, Biolase, USA) by 400 μ tip continuously at 100 mW with 398 J/cm² energy density of tip, which was applied for 5 s at a distance of 2 mm on the axial wall of the cavity. In the control group, irradiation was performed by using the aiming beam. Access cavity was then restored with a composite resin. Cold sensitivity was measured using a cold spray application on the middle third of teeth buccal surface at baseline (before the intervention), 1, 14, and 30 days after the restoration by visual analog scale (VAS) criteria. The mean Friedman and Wilcoxon signed-rank tests were used for data analysis. It was shown that in both laser and control groups, the VAS was significantly decreased at all times compared to the baseline (p ≤ 0.05). There was no statistically significant difference between the mean VAS of two groups at baseline and first day (p ≤ 0.05), but at 14 and 30 days after the intervention, it was significantly lower in the laser group (p ≤ 0.05). The results of this study demonstrated that the cavity pretreatment with laser diode (940 nm) effectively reduces the postoperative sensitivity in class II composite restorations.

     

COVID-19 in Kidney Transplant Patients From a Large UK Transplant Center: Exploring Risk Factors for Disease Severity

BackgroundThe novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has raised concern for the health of immunocompromised individuals, who are potentially at higher risk of more severe infection and poorer outcomes. As a large London transplant center serving a diverse patient population, we report the outcomes of SARS-CoV-2 infection in our cohort of 2848 kidney and/or pancreas transplant patients.MethodsData were obtained retrospectively for all transplant patients who attended hospital during the peak of the pandemic and had a positive nasopharyngeal SARS-CoV-2 test.ResultsSixty-six patients were found to be positive for SARS-CoV-2. Twenty percent were treated as outpatients, 59% were admitted to the general ward, and 21% required intensive care. Treatment consisted of reduced immunosuppression, antibiotics for pneumonia or sepsis, and other supportive treatments. Within our cohort, 12 patients died (18%), with an overall mortality of 0.4%. Predictive risk factors for COVID-19 severity were explored.ConclusionsSevere disease was associated with lower hemoglobin prior to COVID-19 diagnosis and lower lymphocyte count at the time of diagnosis but not age, sex, ethnicity, or preexisting comorbidities. Lower glomerular filtration rate and higher C-reactive protein were associated with more severe disease. Despite no use of hydroxychloroquine, azithromycin, antiviral, or immunomodulatory medications, our mortality rate (kidney and pancreas transplant patients) is similar to current international rates.     

Regulation of Th17 cells by P. UF1 against systemic Listeria monocytogenes infection

Regulation of Th17 and Th1 cell responses against intracellular pathogens, including Listeria monocytogenes (L. m), is critical to limit inflammation-induced tissue damage. We recently demonstrated the ability of P. UF1 bacterium derived from the intestinal bacterial commensals of preterm infants fed human breast milk to significantly mitigate pathogen-induced inflammation limiting colonic tissue damage. Here we further elucidated the potential of P. UF1 to also regulate innate and T cells, particularly Th17 and Th1 cells, against systemic L. m infection. Data demonstrate that P. UF1 not only robustly regulated protective Th17 and Th1 cells, but also sustained regulatory T cells (Treg cells) resulting in accelerated L. m clearance. Together, regulation of pathogenic inflammation by a novel probiotic bacterium such as P. UF1 may illuminate a new strategy to specifically control Th17-Th1 cells via IL-10⁺ Treg cells to limit systemic tissue damage induced by intracellular pathogens, including L. m.     

The association between social support and the mental health of social workers and police officers who work with unaccompanied asylum-seeking refugee children’s forced repatriation: A Swedish experience

This study aims to contribute to the knowledge of social support and its association with mental health amongst social workers and police officers in forced repatriation work of unaccompanied asylum-seeking refugee children. Nationally distributed surveys to social workers and police officers with and without experience of forced repatriation were used, measured by an abbreviated version of the Interview Schedule for Social Interaction (ISSI), and analyzed by univariate and multivariable regression models. Social workers in forced repatriation showed significantly poorer mental health than other social workers, but simultaneously relatively high access to social support. Irrespective of working with forced repatriation, police officers reported relatively high access to social support, but no difference in mental health. Furthermore, low levels of satisfaction with social interaction and close emotional support increased the odds of psychological disturbances for police officers in forced repatriation. Findings are discussed with special regard to the complexity of forced repatriation, particularly when children are the focus.     

Evaluation of Non Diseased Specified Outcome Measures in Hand Injuries to Assess Activity and Participation Based on ICF Content

The objective of the study is to provide information about non disease specified outcome measures which evaluate disability in patients who have impairments in hand and upper extremity and to find the extent to which they are evaluating “disability” based on ICF hand Core Set (activity limitation and participation restriction). MEDLINE, CINAHL, GOOGLE SCHOLAR , OVID and SCIENCE DIRECT databases were systematically searched for studies on non disease specified outcome measures used to evaluate upper extremity function; only studies written in English were considered. We reviewed titles and abstracts of the identified studies to determine whether the studies met predefined eligibility criteria (eg, non disease specified out come measures used in hand injured patients). All the outcome measures which had eligibility included. After full text review ,7 non disease specified outcome measures in hand were identified. Studies were extracted, and the information retrieved from them. All the outcome measures which had incuded, were linked with ICF hand core set disability part (activity and participation). All of them only linked to 16 (42 %) components of ICF hand Core Set, which were most activity and less participation from ICF. None of the non disease specified out come measures in hand injuries cover all domains of disability from the ICF Hand Core Set.