@article{SilvaVilchesPletinckxLohnertetal.2017, author = {Silva-Vilches, Cinthia and Pletinckx, Katrien and Lohnert, Miriam and Pavlovic, Vladimir and Ashour, Diyaaeldin and John, Vini and Vendelova, Emilia and Kneitz, Susanne and Zhou, Jie and Chen, Rena and Reinheckel, Thomas and Mueller, Thomas D. and Bodem, Jochen and Lutz, Manfred B.}, title = {Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {7}, doi = {10.1371/journal.pone.0178114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158244}, pages = {e0178114}, year = {2017}, abstract = {Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3\(^{+}\) induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CT\(^{hi}\), CT\(^{lo}\)) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CT\(^{hi}\) conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CT\(^{lo}\)- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3\(^{+}\) iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CT\(^{lo}\)- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3\(^{+}\) Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.}, language = {en} } @article{EichnerReisDoresetal.2021, author = {Eichner, Felizitas A. and Reis, Joschua M. and Dores, Joaquim and Pavlovic, Vladimir and Kreß, Luisa and Daneshkhah, Naeimeh and Weinhardt, Renate and Grau, Armin and M{\"u}hler, Johannes and Soda, Hassan and Schwarzbach, Christopher J. and Schuler, Michael and H{\"a}usler, Karl Georg and Heuschmann, Peter U.}, title = {Cross-sectional study on patients' understanding and views of the informed consent procedure of a secondary stroke prevention trial}, series = {European Journal of Neurology}, volume = {28}, journal = {European Journal of Neurology}, number = {8}, doi = {10.1111/ene.14917}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259404}, pages = {2639-2647}, year = {2021}, abstract = {Background and purpose Improving understanding of study contents and procedures might enhance recruitment into studies and retention during follow-up. However, data in stroke patients on understanding of the informed consent (IC) procedure are sparse. Methods We conducted a cross-sectional study among ischemic stroke patients taking part in the IC procedure of an ongoing cluster-randomized secondary prevention trial. All aspects of the IC procedure were assessed in an interview using a standardized 20-item questionnaire. Responses were collected within 72 h after the IC procedure and analyzed quantitatively and qualitatively. Participants were also asked their main reasons for participation. Results A total of 146 stroke patients (65 ± 12 years old, 38\% female) were enrolled. On average, patients recalled 66.4\% (95\% confidence interval = 65.2\%-67.5\%) of the content of the IC procedure. Most patients understood that participation was voluntary (99.3\%) and that they had the right to withdraw consent (97.1\%); 79.1\% of the patients recalled the study duration and 56.1\% the goal. Only 40.3\% could clearly state a benefit of participation, and 28.8\% knew their group allocation. Younger age, higher graduation, and allocation to the intervention group were associated with better understanding. Of all patients, 53\% exclusively stated a personal and 22\% an altruistic reason for participation. Conclusions Whereas understanding of patient rights was high, many patients were unable to recall other important aspects of study content and procedures. Increased attention to older and less educated patients may help to enhance understanding in this patient population. Actual recruitment and retention benefit of an improved IC procedure remains to be tested in a randomized trial.}, language = {en} }