Mechanisms of T cell organotropism

F.M.M.-B. is supported by the British Heart Foundation, the Medical Research Council of the UK and the Gates Foundation

The ethic of delicacy in phenomenological research.

In this article, the author works out the conceptual framework of the phenomenological method. The core idea of the article is that the phenomenological method is important in human research because it avoids the logic of control of positivism and adopts a logic of delicacy towards the lived experience of the other. Indeed, it is because of this logic that the phenomenological method is particularly suited to research related to health and well-being, since whenever dealing with suffering and endeavoring to improve the quality of life, accuracy and delicacy are essential. First, the article defines the essence of the phenomenological method in the light of phenomenological philosophy; second, it identifies and investigates what mental acts must be developed in order to put into practice the essence of the phenomenological method. These include paying open attention, being-not-in-search, emptying the mind, experiencing cognitive placelessness, having empathy for the other and caring for the other. The detailed description of these cognitive postures is necessary so that the core of the phenomenological method can be clearly understood

CD62Lneg CD38+ expression on circulating CD4 + T cells identifies mucosally differentiated cells in protein fed mice and in human celiac disease patients and controls

Objectives: The aim of this study was to identify new markers of mucosal T cells to monitor ongoing intestinal immune responses in peripheral blood. Methods: Expression of cell-surface markers was studied in mice on ovalbumin (OVA)-specific T cells in the gut-draining mesenteric lymph nodes (MLN) after OVA feed. The effect of the local mucosal mediators retinoic acid (RA) and transforming growth factor-Β (TGF-Β) on the induction of a mucosal phenotype was determined in in vitro T-cell differentiation assays with murine and human T cells. Tetramer stainings were performed to study gluten-specific T cells in the circulation of patients with celiac disease, a chronic small-intestinal inflammation. Results: In mice, proliferating T cells in MLN were CD62LnegCD38 during both tolerance induction and abrogation of intestinal homeostasis. This mucosal CD62LnegCD38 T-cell phenotype was efficiently induced by RA and TGF-Β in mice, whereas for human CD4 T cells RA alone was sufficient. The CD4 CD62LnegCD38 T-cell phenotype could be used to identify T cells with mucosal origin in human peripheral blood, as expression of the gut-homing chemokine receptor CCR9 and Β 7 integrin were highly enriched in this subset whereas expression of cutaneous leukocyte-associated antigen was almost absent. Tetramer staining revealed that gluten-specific T cells appearing in blood of treated celiac disease patients after oral gluten challenge were predominantly CD4 CD62LnegCD38 . The total percentage of circulating CD62LnegCD38 of CD4 T cells was not an indicator of intestinal inflammation as percentages did not differ between pediatric celiac disease patients, inflammatory bowel disease patients and respective controls. However, the phenotypic selection of mucosal T cells allowed cytokine profiling as upon restimulation of CD62LnegCD38 cells interleukin-10 (IL-10) and interferon-γ (IFN-γ) transcripts were readily detected in circulating mucosal T cells. Conclusions: By selecting for CD62LnegCD38 expression that comprises 5-10% of the cells within the total CD4 T-cell pool we are able to highly enrich for effector T cells with specificity for mucosal antigens. This is of pivotal importance for functional studies as this purification enhances the sensitivity of cytokine detection and cellular activation

The ‘New’ Heidegger

If discussion of “new” approaches to Martin Heidegger contradicts Heidegger’s own indictment of the passion for “novelty” in philosophy, today’s Black Notebooks scandal reminds us of the ontic problem of new news. Indeed the backwards working evidence of the notebooks kept before, during, and after WWII both vindicates and problematizes his notion of temporality temporalizing from the future -- lapsing into the past -- setting up what is now regarded as patent in the present. Simultaneously, we see that if heretofore many philosophers of technology sought to dismiss engagement with Heidegger’s critique of technology, these critical contributions turn out to bear on current issues of transhumanism, technoscience, time, even death (the overcoming of which we eagerly anticipate). Heidegger’s thinking remains to be appropriated