Anti-CTLA-4 treatment induces IL-10-producing ICOS+ regulatory T cells displaying IDO-dependent anti-inflammatory properties in a mouse model of colitis.

BACKGROUND AND AIMS: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) has been shown to act as a negative regulator of T cell function and has been implicated in the regulation of T helper 1 (Th1)/Th2 development and the function of regulatory T cells. Tests were carried out to determine whether anti-CTLA-4 treatment would alter the polarisation of naive T cells in vivo. METHODS: Mice were treated with anti-CTLA-4 monoclonal antibody (mAb) (UC10-4F10) at the time of immunisation or colonic instillation of trinitrobenzene sulfonic acid (TNBS). The cytokines produced by lymph node cells after in vitro antigenic stimulation and the role of indoleamine 2,3 dioxygenase (IDO) and of interleukin-10 (IL-10) were tested, and the survival of mice was monitored. RESULTS: Injection of anti-CTLA-4 mAb in mice during priming induced the development of adaptive CD4(+) regulatory T cells which expressed high levels of ICOS (inducible co-stimulator), secreted IL-4 and IL-10. This treatment inhibited Th1 memory responses in vivo and repressed experimental intestinal inflammation. The anti-CTLA-4-induced amelioration of disease correlated with IDO expression and infiltration of ICOS(high) Foxp3(+) T cells in the intestine, suggesting that anti-CTLA-4 acted indirectly through the development of regulatory T cells producing IL-10 and inducing IDO. CONCLUSIONS: These observations emphasise the synergy between IL-10 and IDO as anti-inflammatory agents and highlight anti-CTLA-4 treatment as a potential novel immunotherapeutic approach for inducing adaptive regulatory T cells.

Das Bistum Münster 10. Das Augustinerchorherrenstift Bernried

Das Augustinerchorherrenstift Bernried ist eine Gründung des 12. Jahrhunderts und beheimatete bis zur Säkularisation 1803 einen Augustinerchorherrenkonvent. Die Stiftung des Grafenpaares Otto und Adelheid von Valley gehörte zu den neuen geistlichen Niederlassungen, die im Zuge der Reformbewegung der Regularkanoniker fundiert wurden. Für die Region um Bernried am Starnberger See wirkte das Stift als gestalterische Kraft über sechs Jahrhunderte hinweg. Großen Aufschwung nahm das Stift erneut im 18. Jahrhundert, als herausragende Pröpste gerade die musikalische Entwicklung des Konventes förderten: einige Pröpste wirkten als Komponisten; von den Musikalien haben sich zahlreiche Handschriften und Instrumente erhalten. Nach dem bewährten Schema der Germania Sacra skizziert die Autorin Walburga Scherbaum kenntnisreich die Geschichte, die Verfassung, das geistige und religiöse Leben, die Besitzgeschichte und vor allem das Personal des Stiftes von seiner Gründung bis zur Aufhebung. Mit diesem Werk werden die Bemühungen der Germania Sacra um die geistlichen Institutionen im Alten Reich um eine weitere geistliche Niederlassung im bayerischen Raum neben Raitenhaslach (Germania Sacra N. F. 11), Dietramszell (Germania Sacra N. F. 24), Benediktbeuern (Germania Sacra N. F. 28) und Wessobrunn (Germania Sacra N. F. 39) bereichert.

Role of mast cells in inflammatory bowel disease and inflammation-associated colorectal neoplasia in IL-10-deficient mice.

BACKGROUND: Inflammatory bowel disease (IBD) is hypothesized to result from stimulation of immune responses against resident intestinal bacteria within a genetically susceptible host. Mast cells may play a critical role in IBD pathogenesis, since they are typically located just beneath the intestinal mucosal barrier and can be activated by bacterial antigens. METHODOLOGY/PRINCIPAL FINDINGS: This study investigated effects of mast cells on inflammation and associated neoplasia in IBD-susceptible interleukin (IL)-10-deficient mice with and without mast cells. IL-10-deficient mast cells produced more pro-inflammatory cytokines in vitro both constitutively and when triggered, compared with wild type mast cells. However despite this enhanced in vitro response, mast cell-sufficient Il10(-/-) mice actually had decreased cecal expression of tumor necrosis factor (TNF) and interferon (IFN)-gamma mRNA, suggesting that mast cells regulate inflammation in vivo. Mast cell deficiency predisposed Il10(-/-) mice to the development of spontaneous colitis and resulted in increased intestinal permeability in vivo that preceded the development of colon inflammation. However, mast cell deficiency did not affect the severity of IBD triggered by non-steroidal anti-inflammatory agents (NSAID) exposure or helicobacter infection that also affect intestinal permeability. CONCLUSIONS/SIGNIFICANCE: Mast cells thus appear to have a primarily protective role within the colonic microenvironment by enhancing the efficacy of the mucosal barrier. In addition, although mast cells were previously implicated in progression of sporadic colon cancers, mast cells did not affect the incidence or severity of colonic neoplasia in this inflammation-associated model.

Long- incubation time- interferon-gamma release assays in response to PPD-, ESAT-6- and/or CFP-10 for the diagnosis of Mycobacterium tuberculosis infection in children.

Background:Diagnosis of childhood active tuberculosis (aTB) or latent Mycobacterium tuberculosis (Mtb) infection (LTBI) remains a challenge, and replacement of tuberculin skin tests (TST) by commercialized interferon-gamma release assays (IGRA) is not currently recommended.Methods:266 children between 1 month and 15 years of age, 214 being at risk of recent Mtb infection and 51 being included as controls, were prospectively enrolled. According results of clinical evaluation, TST, chest X-Ray and microbiology, children were classified as non-infected, LTBI or aTB. Long-incubation time PPD-, ESAT-6-, and CFP-10-IGRA were performed and evaluated for their accuracy to correctly classify the children.Results:Whereas both TST and PPD-IGRA were suboptimal to detect aTB, combining CFP-10-IGRA with TST or with PPD-IGRA allowed us to detect all the children with aTB, with 96% specificity for children who were positive for CFP-10-IGRA. Moreover, combination of CFP-10- and PPD-IGRA also detected 96% of children classified as LTBI, but a strong IFN-γ response to CFP-10 (>500 pg/ml) was highly suggestive of aTB at least among children less than 3 years old.Conclusions:Long-incubation time CFP-10- and PPD-IGRA should help the clinicians to identify quickly aTB or LTBI in young children.

Archaeological Testing at 10 Francis Street, Annapolis, Maryland, 18AP55

In August 1990, archaeological investigations were permitted at 10 Francis Street (18AP55). The house on this property dates to the early eighteenth century and the property has had little disturbance since that time. Excavation here has provided an excellent opportunity to learn more about this period of Annapolis' history. Two units were excavated and are described fully within this report. One unit, placed next to the house foundation, revealed an eighteenth-century brick sidewalk beneath the current mid-nineteenth-century brick sidewalk, but it did not contain any builder's trench for the structure. A second unit, randomly place in the back yard, revealed intact stratigraphy dating back to the early eighteenth century. These findings demonstrate the integrity of this site and its potential for future investigation. Any alterations to this property should proceed only after further controlled excavations have taken place.

Monocyte-derived interleukin-10 depresses the Bordetella pertussis- specific gamma interferon response in vaccinated infants.

Antigen-specific gamma interferon (IFN-gamma) has been demonstrated to participate in protection against Bordetella pertussis infection. Circulating mononuclear cells from B. pertussis-infected and from pertussis-vaccinated infants secrete high amounts of IFN-gamma after in vitro stimulation by B. pertussis antigens, but with a large variation in the secreted IFN-gamma levels between individuals. We show here that the inhibition of the specific IFN-gamma response can be at least partially attributed to IL-10 secretion by monocytes. This IL-10 secretion was not associated with polymorphisms at positions -1082, -819, and -592 of the IL-10 gene promoter, suggesting that other genetic or environmental factors affect IL-10 expression and secretion.

Molecular dissociation of FHA-induced IL-10 and IL-12 secretion by human dendritic cells.

info:eu-repo/semantics/nonPublished

Role of the IL-10/IL-12 balance in the primary cellular immune response of infants to pertussis vaccines

info:eu-repo/semantics/nonPublished

Effects of different molecular forms of FHA on IL-10 and IL-12 secretions by human dendritic cells.

info:eu-repo/semantics/nonPublished

Caracterización de las heladas en la región pampeana y su variabilidad en los últimos 10 años

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El proceso de modelación matemática en las aulas escolares. A propósito de los 10 años de su inclusión en los lineamientos curriculares colombianos

En este documento se presentan algunos elementos que permiten reflexionar sobre el proceso de modelación como estrategia didáctica para abordar la construcción de conceptos matemáticos en el aula de clase. Estos elementos se convierten en un avance de la investigación en curso “El proceso de modelación en las aulas escolares del suroeste antioqueño” financiado por el Comité para el desarrollo de la investigación (CODI) y la Dirección de Regionalización de la Universidad de Antioquia.

imátgenes 10, 11 y 12

Fue el último en poseerla quien, instantes antes de perderla para siempre y movido por una presunción ya del todo instintiva, bautizó la ciudad con el nombre de Memoria grafiando esa palabra en las fachadas de las avenidas. Presumió que en un futuro, muy lejano quizá pero alcanzable, y a pesar de los trazos ya inseguros de su escritura afectada, alguien podría leerla y recobrar la lucidez.

Psychology and interventions for pupils at risk of underachievement and school exclusion: the year 10 effect

Findings are presented from a longitudinal study of over 1,500 adolescents. Some were engaged in interventions aimed at reducing social disaffection. Participants completed measures of social-identification, academic self-concept and motivation, and social, emotional and behavioural difficulties. Consistent with our previous research, developmental trends in identity and self-concept were found - adolescents became more negative about some school-based factors and more positive about aspects of identity. Trends were less clear in the 120 adolescents receiving interventions. Findings demonstrate the importance of psychology in work with young people. [Source: (2008) 'Invited Address, IUPsyS Invited Symposium, Invited Symposium, Symposium, Paper Session, Poster Session', International Journal of Psychology, 43:3, 348 - 527]