Spatiotemporal in vivo tracking of polyclonal human regulatory T cells (Tregs) reveals a role for innate immune cells in Treg transplant recruitment

Supplemental information is available online at: https://www.sciencedirect.com/science/article/pii/S2329050120302515#appsec2 .Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs has been shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive, which hampers clinical translation. Here we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behavior, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nano-single-photon emission computed tomography (nanoSPECT)/computed tomography (CT) for up to 40 days, and the results were validated ex vivo. Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1+ innate immune cells. We demonstrated the utility of radionuclide reporter gene-afforded quantitative Treg in vivo tracking, addressing a fundamental need in Treg therapy development and offering a clinically compatible methodology for future Treg therapy imaging in humans.This work was supported by the British Heart Foundation (RG/13/12/30395), the MRC Centre for Transplantation at King's College London (MR/J006742/1), Cancer Research UK (C48390/A21153), and the Wellcome/EPSRC Centre for Medical Engineering (WT203148/Z/16/Z). This research was funded/supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London and/or the NIHR Clinical Research Facility

Sistema soporte de decisiones para empresas industriales: diseño de la base de modelos

En este trabajo presentamos el diseño conceptual de la. estructura de la Base de Modelos de un Sistema Soporte de Decisiones para empresas industriales dedicadas a la elaboración de varios productos. La Base de Modelos se representa mediante una estructura modular especificando la función de cada módulo en el proceso de soporte de decisiónEje: AplicacionesRed de Universidades con Carreras en Informática (RedUNCI

Spatiotemporal in vivo tracking of polyclonal human regulatory T cells reveals a role for innate immune cells in Treg transplant recruitment

Regulatory T cells (Tregs) are emerging as a new cell-based therapy in solid organ transplantation. Adoptive transfer of Tregs was shown preclinically to protect from graft rejection, and the safety of Treg therapy has been demonstrated in clinical trials. Despite these successes, the in vivo distribution and persistence of adoptively transferred Tregs remained elusive which hampers clinical translation. Here, we isolated human Tregs using a GMP-compatible protocol and lentivirally transduced them with the human sodium iodide symporter to render them traceable in vivo by radionuclide imaging. Engineered human Tregs were characterized for phenotype, survival, suppressive capacity, and reporter function. To study their trafficking behaviour, they were subsequently administered to humanized mice with human skin transplants. Traceable Tregs were quantified in skin grafts by non-invasive nanoSPECT/CT for up to 40 days and results validated ex vivo. Using this approach, we demonstrated that Treg trafficking to skin grafts was regulated by the presence of recipient Gr-1⁺ innate immune cells. We demonstrated the utility of radionuclide reporter gene afforded quantitative Treg in vivo tracking thereby addressing a fundamental need in Treg therapy development and offering clinically compatible methodology for future Treg therapy imaging in humans

Sistema soporte de decisiones para empresas industriales: diseño de la base de modelos

En este trabajo presentamos el diseño conceptual de la. estructura de la Base de Modelos de un Sistema Soporte de Decisiones para empresas industriales dedicadas a la elaboración de varios productos. La Base de Modelos se representa mediante una estructura modular especificando la función de cada módulo en el proceso de soporte de decisiónEje: AplicacionesRed de Universidades con Carreras en Informática (RedUNCI

Sistema soporte de decisiones para empresas industriales: diseño de la base de modelos

En este trabajo presentamos el diseño conceptual de la. estructura de la Base de Modelos de un Sistema Soporte de Decisiones para empresas industriales dedicadas a la elaboración de varios productos. La Base de Modelos se representa mediante una estructura modular especificando la función de cada módulo en el proceso de soporte de decisiónEje: AplicacionesRed de Universidades con Carreras en Informática (RedUNCI

TA treatment of depression: a hermeneutic single-case efficacy design study- 'Penelope'

This study is the second of a series of three, and represents an Italian replication of a previous UK -based case series (Widdowson 2012a, 2012b, 2012c, 2013) that investigated the effectiveness of a recently manualised transactional analysis treatment for depression with British clients, using Hermeneutic Single-Case Efficacy Design (HSCED). The various stages of HSCED as a systematic case study research method are described, as a quasi-judicial method to sift case evidence in which researchers construct opposing arguments around multiple sources of quantitative and qualitative evidence and judges evaluate these to conclude whether the client changed substantially over the course of therapy, and whether the outcome was attributable to the therapy. The therapist in this case was a white Italian man in the third year of training to become a psychotherapist, and the client, Penelope, was a 45- year old white Italian woman with mild depression and anxiety. The conclusion of the judges was that this was a mixed-outcome case: the client improved some aspects of her problems, without obtaining a complete and stable remission. Interestingly, this case presents a minimal correlation between empirical and proxy-rated indexes of depression and anxiety and answers to self reported questionnaires, raising the question of validity of self report measures with specific typology of client

Inflammatory bowel disease in children and adolescents in Italy: data from the pediatric national IBD register (1996-2003).

Abstract BACKGROUND: The purpose was to assess in Italy the clinical features at diagnosis of inflammatory bowel disease (IBD) in children. METHODS: In 1996 an IBD register of disease onset was established on a national scale. RESULTS: Up to the end of 2003, 1576 cases of pediatric IBD were recorded: 810 (52%) ulcerative colitis (UC), 635 (40%) Crohn's disease (CD), and 131 (8%) indeterminate colitis (IC). In the period 1996-2003 an increase of IBD incidence from 0.89 to 1.39/10(5) inhabitants aged <18 years was observed. IBD was more frequent among children aged between 6 and 12 years (57%) but 20% of patients had onset of the disease under 6 years of age; 28 patients were <1 year of age. Overall, 11% had 1 or more family members with IBD. The mean interval between onset of symptoms and diagnosis was higher in CD (10.1 months) and IC (9 months) versus UC (5.8 months). Extended colitis was the most frequent form in UC and ileocolic involvement the most frequent in CD. Upper intestinal tract involvement was present in 11% of CD patients. IC locations were similar to those of UC. Bloody diarrhea and abdominal pain were the most frequent symptoms in UC and IC, and abdominal pain and diarrhea in CD. Extraintestinal symptoms were more frequent in CD than in UC. CONCLUSIONS: The IBD incidence in children and adolescents in Italy shows an increasing trend for all 3 pathologies. UC diagnoses exceeded CD