Adoptive Cell Therapy in Mice Sensitized to a Grass Pollen Allergen.

The proportion of patients with type I allergy in the world population has been increasing and with it the number of people suffering from allergic symptoms. Recently we showed that prophylactic cell therapy employing allergen-expressing bone marrow (BM) cells or splenic B cells induced allergen-specific tolerance in naïve mice. Here we investigated if cell therapy can modulate an established secondary allergen-specific immune response in pre-immunized mice. We sensitized mice against the grass pollen allergen Phl p 5 and an unrelated control allergen, Bet v 1, from birch pollen before the transfer of Phl p 5-expressing BM cells. Mice were conditioned with several combinations of low-dose irradiation, costimulation blockade, rapamycin and T cell-depleting anti-thymocyte globulin (ATG). Levels of allergen-specific IgE and IgG1 in serum after cell transfer were measured via ELISA and alterations in cellular responses were measured via an in vitro proliferation assay and transplantation of Phl p 5+ skin grafts. None of the tested treatment protocols impacted Phl p 5-specific antibody levels. Transient low-level chimerism of Phl p 5+ leukocytes as well as a markedly prolonged skin graft survival were observed in mice conditioned with high numbers of Phl p 5+ BMC or no sensitization events between the day of cell therapy and skin grafting. The data presented herein demonstrate that a pre-existing secondary allergen-specific immune response poses a substantial hurdle opposing tolerization through cell therapy and underscore the importance of prophylactic approaches for the prevention of IgE-mediated allergy.

Epigenetic modulation of myeloid cell functions in HIV and SARS-CoV-2 infection.

Myeloid cells play a vital role in innate immune responses as they recognize and phagocytose pathogens like viruses, present antigens, produce cytokines, recruit other immune cells to combat infections, and contribute to the attenuation of immune responses to restore homeostasis. Signal integration by pathogen recognition receptors enables myeloid cells to adapt their functions by a network of transcription factors and chromatin remodelers. This review provides a brief overview of the subtypes of myeloid cells and the main epigenetic regulation mechanisms. Special focus is placed on the epigenomic alterations in viral nucleic acids of HIV and SARS-CoV-2 along with the epigenetic changes in the host's myeloid cell compartment. These changes are important as they lead to immune suppression and promote the progression of the disease. Finally, we highlight some promising examples of 'epidrugs' that modulate the epigenome of immune cells and could be used as therapeutics for viral infections.

Vascular Responses following Light Therapy: A Pilot Study with Healthy Volunteers.

(1) Background: Studies have reported the effectiveness of light therapy in various medical conditions. Our pilot study aimed to assess the effect of Maharishi light therapy (MLT) on physiological parameters, such as the heart rate (HR), HR variability (HRV), blood pressure (BP), BP variability (BPV), and the retinal microvasculature of healthy participants; (2) Methodology: Thirty (14 males and 16 females) healthy, non-smoking participants between 23 and 71 years old (46 ± 18 years) were included in this randomized crossover study. Each participant was tested with a placebo (using LED light) and gem lights, 24 h apart. Hemodynamic parameters were recorded during the session, and 24 h heart rate and BP levels were assessed via mobile devices. Retinal vascular responses were captured with fundus images and the subsequent analysis of retinal vessel widths. A linear model, using repeated measures ANOVA, was used to compare the responses across the sexes and to assess the effect of the MLT; (3) Results: Changes in the central retinal artery equivalent (CRAE) (p < 0.001) and central retinal vein equivalent (CRVE) (p = 0.002) parameters were observed. CRAE and CRVE decreased under MLT and increased under the placebo condition from before to after. However, the baseline values of the participants already differed significantly before the application of any therapy, and the variation in the retinal vessel diameters was already large in the baseline measurements. This suggests that the observed effect results may only reflect naturally occurring fluctuations in the microcirculation and not the effect of MLT. Furthermore, no significant effects were observed in any other investigated parameters; (4) Conclusion: Our study with healthy participants finds significant changes in retinal parameters, but the biological variation in the baseline measurements was large to begin with. This suggests that the observed effect results only reflect naturally occurring fluctuations in the microcirculation and not the effect of MLT. However, in the future, larger studies in which MLT is applied for longer periods and/or in patients with different diseases could discover the physiological impacts of this type of therapy.

Target Selection for T-Cell Therapy in Epithelial Ovarian Cancer: Systematic Prioritization of Self-Antigens.

Adoptive T cell-receptor therapy (ACT) could represent a promising approach in the targeted treatment of epithelial ovarian cancer (EOC). However, the identification of suitable tumor-associated antigens (TAAs) as targets is challenging. We identified and prioritized TAAs for ACT and other immunotherapeutic interventions in EOC. A comprehensive list of pre-described TAAs was created and candidates were prioritized, using predefined weighted criteria. Highly ranked TAAs were immunohistochemically stained in a tissue microarray of 58 EOC samples to identify associations of TAA expression with grade, stage, response to platinum, and prognosis. Preselection based on expression data resulted in 38 TAAs, which were prioritized. Along with already published Cyclin A1, the TAAs KIF20A, CT45, and LY6K emerged as most promising targets, with high expression in EOC samples and several identified peptides in ligandome analysis. Expression of these TAAs showed prognostic relevance independent of molecular subtypes. By using a systematic vetting algorithm, we identified KIF20A, CT45, and LY6K to be promising candidates for immunotherapy in EOC. Results are supported by IHC and HLA-ligandome data. The described method might be helpful for the prioritization of TAAs in other tumor entities.

How stable is lung function in patients with stable chronic obstructive pulmonary disease when monitored using a telehealth system? A longitudinal and home-based study.

BACKGROUND: Many telehealth systems have been designed to identify signs of exacerbations in patients with chronic obstructive pulmonary disease (COPD), but few previous studies have reported the nature of recorded lung function data and what variations to expect in this group of individuals. The aim of the study was to evaluate the nature of individual diurnal, day-to-day and long-term variation in important prognostic markers of COPD exacerbations by employing a telehealth system developed in-house. METHODS: Eight women and five men with COPD performed measurements (spirometry, pulse oximetry and the COPD assessment test (CAT)) three times per week for 4-6 months using the telehealth system. Short-term and long-term individual variations were assessed using the relative density and weekly means respectively. Quality of the spirometry measurements (forced expiratory volume in one second (FEV1) and inspiratory capacity (IC)) was assessed employing the criteria of American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines. RESULTS: Close to 1100 measurements of both FEV1 and IC were performed during a total of 240 patient weeks. The two standard deviation ranges for intra-individual short-term variation were approximately ±210 mL and ± 350 mL for FEV1 and IC respectively. In long-term, spirometry values increased and decreased without notable changes in symptoms as reported by CAT, although it was unusual with a decrease of more than 50 mL per measurement of FEV1 between three consecutive measurement days. No exacerbation occurred. There was a moderate to strong positive correlation between FEV1 and IC, but weak or absent correlation with the other prognostic markers in the majority of the participants. CONCLUSIONS: Although FEV1 and IC varied within a noticeable range, no corresponding change in symptoms occurred. Therefore, this study reveals important and, to our knowledge, previously not reported information about short and long-term variability in prognostic markers in stable patients with COPD. The present data are of significance when defining criteria for detecting exacerbations using telehealth strategies.