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.

     

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.     

Silver nanoparticles production by two soil isolated bacteria,Bacillus thuringiensis and Enterobacter cloacae,and assessment of their cytotoxicity and wound healing effect in rats

Production of silver nanoparticles by Bacillus thuringiensis and Enterobacter cloacae was performed and confirmed through UV–visible spectrophotometry, transmission electron microscopy (TEM), and x‐ray diffraction (XRD) analyses. The 3‐(4,5‐dimethylthiazol‐2‐yl)?2,5‐diphenyltetrazolium bromide (MTT) assay using mouse fibroblast cell line NIH‐3T3 D4 was carried out and IC_50s of AgNPs were obtained. The nontoxic dose of each AgNPs solution was selected for wound healing assay. Thirty‐two rats were divided into four groups; two were used as the controls and two were treated by AgNPs that were produced by two bacterial strains. Results revealed that the produced AgNPs were amorphous, spherical in shapes, and had sizes under 100 nm. Histological analysis showed that AgNPs had better wound healing efficacy than the control groups. In conclusion, when the biologically produced AgNPs were used in vivo, they induced the epithelization, formation of the collagen bundles and fibroplasia and reduced the duration of completion of the epithelization and the angiogenesis.