Distinct phenotypes of antigen-selected CD8 T cells emerge at different stages of an in vivo immune response.

We have previously described a unique system for identifying Ag-selected CD8 T cells during an in vivo response in normal mice. In this system, lymphocytes isolated from DBA/2 mice injected i.p. with HLA-CW3 transfected syngeneic (H-2d) P815 cells show a remarkable expansion of CD8 cells that utilize TCR expressing the V beta 10 gene segment and additional structural features characteristic of Kd-restricted CW3-specific CTL clones. We have now taken advantage of this system to characterize the surface phenotype of CD8 cells selected by Ag in vivo. We observed several distinct phenotypes at different stages of the response. At the peak of the response, Ag-selected cells were low in CD62L and CD45RB expression but displayed high levels of CD44. In addition, there was a partial down-regulation of CD8 and TCR. Cells of this phenotype were present in lymphoid tissues for several mo after immunization. Much later in the response, Ag-selected cells expressed higher levels of CD8 and TCR. Moreover, a distinct subset of these long-term immune cells emerged that now expressed CD62L and CD45RB. Analysis of CD8 cells from different tissues also revealed certain differences, particularly in TCR and co-receptor levels from liver-derived cells compared with circulating cells at the peak of the response. Our findings suggest that the function of Ag-selected CD8 cells may be regulated over time and according to location by subtle changes in cell-surface phenotype.

Interpretarium: una propuesta de plataforma educativa Moodle para la enseñanza-aprendizaje en línea de la Interpretación

Dentro del Espacio Europeo de Educación Superior, las nuevas tecnologías se han convertido en la herramienta por excelencia del aprendizaje, como lo demuestra la multiplicación de los campus virtuales. Los programas informáticos para la formación en interpretación, si bien ofrecen recursos valiosos para la práctica, siguen siendo escasos y su acceso muy restringido. El propósito de nuestro proyecto es proponer un dispositivo que una todos los recursos necesarios para formarse en interpretación y saque mayor provecho del desarrollo reciente de plataformas educativas. Así, planteamos la creación de Interpretarium mediante la plataforma Moodle, cuyas funcionalidades permiten no sólo subsanar las carencias de los proyectos anteriores sino también potenciar una enseñanza-aprendizaje reflexiva y cooperativa en línea. El diseño de la versión test de Interpretarium constituye el primer paso de un proceso de innovación docente para el que la colaboración de sus usuarios (docentes, estudiantes y profesionales de la interpretación) es esencial.

Interpreting in Iceland

The idea of this project is to study the profession of interpreter in Iceland going through different aspects like the need of interpreters in the country, the steps to follow to become an interpreter, the existing means in order to be able to develop the profession or how the future looks like.

TCR-MHC class II interaction is required for peripheral expansion of CD4 cells in a T cell-deficient host.

It is well established that T cell-deficient nude and SCID mice can be reconstituted by i.v. injection of small numbers of purified peripheral CD4+ T cells; however, the requirements for expansion of the transferred T cells in such systems are not clear. We show here that blood and lymphoid organs of MHC class II-deficient mice (which selectively lack mature CD4+ T cells) cannot be reconstituted by transfer of purified splenic CD4+ T cells, whereas TCRalpha-deficient mice (which lack both CD4+ and CD8+ mature T cells) are readily reconstituted. The failure of CD4+ T cell reconstitution in MHC class II-deficient mice was not due to the presence of CD8+ T cells, since similar results were obtained in TCRalpha-MHC class II double-deficient mice. Consistent with most previous studies CD4+ T cells in reconstituted TCRalpha-deficient mice had a diverse TCR Vbeta repertoire and were predominantly of an activated/memory (CD44high) phenotype. Collectively our data demonstrate that the expansion of peripheral CD4+ T cells in a T cell-deficient host is dependent upon interactions of the TCR with MHC class II.

Homeostasis limits the development of mature CD8+ but not CD4+ thymocytes.

The involvement of a variety of clonal selection processes during the development of T lymphocytes in the thymus has been well established. Less information, however, is available on how homeostatic mechanisms may regulate the generation and maturation of thymocytes. To investigate this question, mixed radiation bone marrow chimeras were established in which wild-type T cell precursors capable of full maturation were diluted with precursors deficient in maturation potential because of targeted mutations of the RAG1 or TCR-alpha genes. In chimeras in which the majority of thymocytes are blocked at the CD4- CD8- CD25+ stage (RAG1 deficient), and only a small proportion of T cell precursors are of wild-type origin, we observed no difference in the maturation of wild-type CD4- CD8- CD25+ cells to the CD4+ CD8+ stage as compared with control chimeras. Therefore, the number of cell divisions occurring during this transition is fixed and not subject to homeostatic regulation. In contrast, in mixed chimeras in which the majority of thymocytes are blocked at the CD4+ CD8+ stage (TCR-alpha deficient), an increased efficiency of development of wild-type mature CD8+ cells was observed. Surprisingly, the rate of generation of mature CD4+ thymocytes was not affected in these chimeras. Thus, the number of selectable CD8 lineage thymocytes apparently saturates the selection mechanism in normal mice while the development of CD4 lineage cells seems to be limited only by the expression of a suitable TCR. These data may open the way to the identification of homeostatic mechanisms regulating thymic output and CD4/CD8 lineage commitment, and the development of means to modulate it.

El bilingüismo en la interpretación. Estudio comparativo entre los tipos de bilingüismo enfocado a la interpretación

Este trabajo delimita el término bilingüismo y define los diferentes tipos estudiando qué relevancia tienen (ventajas y/o desventajas) en la interpretación. Se estudia si algún tipo de bilingüismo ofrece mayor predisposición para interpretar. Concluye con un experimento de Think Aloud Protocol (TAP) a estudiantes de interpretación castellano-alemán.

Thymic lineage commitment rather than selection causes genetic variations in size of CD4 and CD8 compartments.

During their development, immature CD4+ CD8+ thymocytes become committed to either the CD4 or CD8 lineage. Subsequent complete maturation of CD4+ and CD8+ cells requires a molecular match of the expressed coreceptor and the MHC specificity of the TCR. The final size of the mature CD4+ and CD8+ thymic compartments is therefore determined by a combination of lineage commitment and TCR-mediated selection. In humans and mice, the relative size of CD4+ and CD8+ peripheral T cell compartments shows marked genetic variability. We show here that genetic variations in thymic lineage commitment, rather than TCR-mediated selection processes, are responsible for the distinct CD4/CD8 ratios observed in common inbred mouse strains. Genetic variations in the regulation of lineage commitment open new ways to analyze this process and to identify the molecules involved.

An adult thymic stromal-cell suspension model for in vitro positive selection.

Presented here is a cell-suspension model for positive selection using thymocytes from alphabeta-TCR (H-2Db-restricted) transgenic mice specific to the lymphocytic choriomeningitis virus (LCMV) on a nonselecting MHC background (H-2d or TAP-1 -/-), cocultured with freshly isolated adult thymus stromal cells of the selecting MHC type. The thymic stromal cells alone induced positive selection of functional CD4- CD8+ cells whose kinetics and efficiency were enhanced by nominal peptide. Fibroblasts expressing the selecting MHC alone did not induce positive selection; however, together with nonselecting stroma and nominal peptide, there was inefficient positive. These results suggest multiple signaling in positive selection with selection events able to occur on multiple-cell types. The ease with which this model can be manipulated should greatly facilitate the resolution of the mechanisms of positive selection in normal and pathological states.

The role of the T-cell receptor (TCR) in alpha beta/gamma delta lineage commitment: clues from intracellular TCR staining.

T cells belong to two mutually exclusive lineages expressing either alpha beta or gamma delta T-cell receptors (TCR). Although alpha beta and gamma delta cells are known to share a common precursor the role of TCR rearrangement and specificity in the lineage commitment process is controversial. Instructive lineage commitment models endow the alpha beta or gamma delta TCR with a deterministic role in lineage choice, whereas separate lineage models invoke TCR-independent lineage commitment followed by TCR-dependent selection and maturation of alpha beta and gamma delta cells. Here we review the published data pertaining to the role of the TCR in alpha beta/gamma delta lineage commitment and provide some additional information obtained from recent intracellular TCR staining studies. We conclude that a variant of the separate lineage model is best able to accommodate all of the available experimental results.

A limited role for beta-selection during gamma delta T cell development.

T cells belong to two distinct lineages expressing either alpha beta or gamma delta TCR. During alpha beta T cell development, it is clearly established that productive rearrangement at the TCR beta locus in immature precursor cells leads to the expression of a pre-TCR complex. Signaling through the pre-TCR results in the selective proliferation and maturation of TCR beta+ cells, a process that is known as beta-selection. However, the potential role of beta-selection during gamma delta T cell development is controversial. Whereas PCR-RFLP and sequencing techniques have provided evidence for a bias toward in-frame VDJ beta rearrangements in gamma delta cells (consistent with beta-selection), gamma delta cells apparently develop normally in mice that are unable to assemble a pre-TCR complex due to a deficiency in TCR beta or pT alpha genes. In this report, we have directly addressed the physiologic significance of beta-selection during gamma delta cell development in normal mice by quantitating intracellular TCR beta protein in gamma delta cells and correlating its presence with cell cycle status. Our results indicate that beta-selection plays a significant (although limited) role in gamma delta cell development by selectively amplifying a minor subset of gamma delta precursor cells with productively rearranged TCR beta genes.

Identification and characterization of the Arabidopsis PHO1 gene involved in phosphate loading to the xylem.

The Arabidopsis mutant pho1 is deficient in the transfer of Pi from root epidermal and cortical cells to the xylem. The PHO1 gene was identified by a map-based cloning strategy. The N-terminal half of PHO1 is mainly hydrophilic, whereas the C-terminal half has six potential membrane-spanning domains. PHO1 shows no homology with any characterized solute transporter, including the family of H(+)-Pi cotransporters identified in plants and fungi. PHO1 shows highest homology with the Rcm1 mammalian receptor for xenotropic murine leukemia retroviruses and with the Saccharomyces cerevisiae Syg1 protein involved in the mating pheromone signal transduction pathway. PHO1 is expressed predominantly in the roots and is upregulated weakly under Pi stress. Studies with PHO1 promoter-beta-glucuronidase constructs reveal predominant expression of the PHO1 promoter in the stelar cells of the root and the lower part of the hypocotyl. There also is beta-glucuronidase staining of endodermal cells that are adjacent to the protoxylem vessels. The Arabidopsis genome contains 10 additional genes showing homology with PHO1. Thus, PHO1 defines a novel class of proteins involved in ion transport in plants.

La interpretación judicial: el intérprete de la Ciutat de la Justícia

El presente trabajo pretende ser un reflejo de la realidad del intérprete judicial en los juzgados de Barcelona. En el primer bloque hemos realizado un breve repaso bibliográfico. En el segundo, un estudio de campo que muestra cómo es el intérprete de la Ciutat de la Justícia y cómo trabaja.

Superantigens of mouse mammary tumor virus.

Superantigens (SAgs) are proteins of microbial origin that bind to major histocompatibility complex (MHC) class II molecules and stimulate T cells via interaction with the V beta domain of the T cell receptor (TCR). Mouse mammary tumor virus (MMTV) is a milk-transmitted type B retrovirus that encodes a SAg in its 3' long terminal repeat. Upon MMTV infection, B cells present SAg to the appropriate T cell subset, which leads to a strong "cognate" T-B interaction. This immune reaction results in preferential clonal expansion of infected B cells and differentiation of some of these cells into long-lived memory cells. In this way a stable MMTV infection is achieved that ultimately results in infection of the mammary gland and virus transmission via milk. Thus, in contrast to many microorganisms that attempt to evade the host immune system (reviewed in 1), MMTV depends upon a strong SAg-induced immune response for its survival. Because of their ability to stimulate very strong T cell responses in MHC-identical mice, minor lymphocyte stimulatory (Mls) antigens, discovered more than 20 years ago, are now known to be SAgs encoded by endogenous MMTV proviruses that have randomly integrated into germ cells. The aim of this review is to combine the extensive biology of Mls SAgs with our current understanding of the life cycle of MMTV.

Pelaamisen lumo : tietokoneella pelaaminen terapeuttisena toimintana

Opinnäytetyön tarkoituksena on käsitellä pelaamista toimintana ja tarkastella pelaamista terapeuttisen toiminnan käsitteellisen viitekehyksen kautta. Tavoitteena on löytää perusteita tietokonepelien käyttöön lasten ja nuorten toimintaterapiassa. Opinnäytetyöprosessiani on ohjannut David L. Nelsonin ja Julie Jepson-Thomasin Terapeuttisen toiminnan käsitteellinen viitekehys. Viitekehyksen avulla tutkin millaista terapeuttista toimintaa pelaaminen on. Opinnäytetyön teoriapohja perustuu eri ammattialojen yleisiin pelitutkimuksiin, koska tietokoneella pelaamisen terapeuttisia vaikutuksia on tutkittu hyvin vähän kuntoutuksen näkökulmasta. Opinnäytetyö on laadullinen. Haastattelin kolmea nuorta poikaa heidän pelikokemuksistaan. Opinnäytetyön teoriasta ja aineistosta löytyi useita pelaamiseen vaikuttavia tekijöitä. Niiden perusteella tietokonepelien käyttö lasten ja nuorten toimintaterapiassa on perusteltua koska pelaaminen on lapsille ja nuorille tärkeää ja hyvin motivoivaa toimintaa. Se on merkittävä terapeuttinen tekijä sekä asiakaskeskeisen työskentelytavan ydin. Terapeuttisen toiminnan käsitteellisen viitekehyksen mukaan toiminnan mukautuminen on sitä kun pelaamalla pelaaja muuttaa itseään. Se antaa terapeutille mahdollisuuden työskennellä asiakkaansa tavoitteiden kanssa asiakkaalle hyvin merkityksellisen toiminnan avulla. Terapeutin ja asiakkaan tarkoitukset toiminnalle voivat olla erilaiset, pelaaminen mahdollistaa ne. Toiminnan mukautumista voi tapahtua kaikessa pelaajan kehityksellisessä rakenteessa: sensomotorisessa, kognitiivisessa ja psykososiaalisessa rakenteessa. Pelitutkijoiden tutkimus tukee johtopäätöstä. Pelaamista voi siten käyttää hyvin monen erilaisen asiakasryhmän kanssa. Pelaaminen myös mahdollistaa tavoitteiden toteutuksen varioinnin, tavoitetta voi harjoitella ja kehittää monilla erilaisilla peleillä. Pelaamisen tärkein terapeuttinen tekijä on eläytymisen mahdollisuus. Pelien avulla voi esimerkiksi liikuntavammainen asiakas kokea liikkumisen iloa. Pelaaminen tarjoaa terapeuttisesti tärkeitä voimaannuttavia tekijöitä. Tietokoneella pelaaminen terapeuttisena toimintana on vain yksi osa tavoitteellista terapiaprosessia, ei koskaan ainoa toiminnan muoto. Terapeuttisena toimintana pelaaminen ei ole itsetarkoitus, vaan se mitä pelaaminen mahdollistaa. Tietokoneen terapeuttisessa käytössä täytyy huomioida ja tiedostaa sen rajoitteet. Tietokoneen käyttäminen ei ole aina helppoa ja se on huomattava taloudellinen ja ajallinen resurssi. Siihen voi liittyä myös tekijöitä jotka vähentävät tai jopa poistavat sen terapeuttista vaikutusta.