1,721,116 research outputs found
Role of regulatory T cells and FOXP3 in human diseases
No full textImmune regulation and tolerance are specific functions ofthe immune system, meaning at prevention or limitation ofeffector immune responses against inner and external insults.Regulatory T (Treg) cells are crucial players in this immunebalance network. Research over the last 10 years hassignificantly contributed to characterizing Treg cell features,their mechanisms of function, and their role in humanpathologies. The discovery of FOXP3 as an essentialtranscription factor not only for differentiation and functionof naturally occurring Treg cells but also for regulationof intracellular molecules related to effector T-cellresponses has provided new insights into the pathogenesisof immune-mediated diseases. Interestingly, there is increasingevidence that the individual signature of genes relevantfor immune regulation definitely influences the final outcomeof an immune response
CD4+ regulatory T cells: mechanisms of induction and effector function
No full texthe main subsets of CD4(+) regulatory T (Tr) cells are the CD4(+) CD25(+) Tr cells and the type 1 regulatory (Tr1) cells. Both subsets are essential for the maintenance of peripheral tolerance. CD4(+) CD25(+) Tr cells control immune homeostasis (e.g., in autoimmunity) mainly by cell contact-dependent interactions. In contrast, Tr1 cells regulate immune responses in transplantation, allergy, and autoirnmune diseases, via an IL-10- and TGF-beta-dependent mechanism. Identification of the mechanisms responsible for the induction of the different Tr subsets in vivo is a matter of intense investigation. Studies on dendritic cells (DC), performed in the last years by several groups, have significantly contributed to clarify this point. Indeed, it is now clear that the role of DCs is not only to sense danger, but also to tolerize the immune system to antigens (Ags) encountered in the absence of maturation/inflammatory stimuli. Therefore, if a naive T cell encounters the antigen on immature DCs (iDCs), it differentiates into a Tr cell rather than an effector T cell.
A better understanding of the mechanisms underlying the induction and functions of Tr cells in controlling the immune system is critical in view of a future cellular therapy to modulate immune-mediated pathologies
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The role of IL-10 and TGF-beta in the differentiation and effector function of T regulatoy cells
No full textSuppression by T regulatory (Tr) cells is essential for the induction of peripheral tolerance. Many types of CD4+ Tr cells have been described in a number of systems, and although the precise mechanisms which mediate their effects remain to be defined, it is well established that they can suppress immune responses via cell-cell interactions and/or the production of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). Type 1 T regulatory (Tr1) cells are defined by their ability to produce high levels of IL-10 and TGF-beta, and these cytokines mediate their ability to suppress pathological immune responses in the settings of transplantation, allergy and autoimmune disease. TO cell activity is not necessarily beneficial, and they can also suppress immune responses to antigens from tumours and pathogens. In vivo, the differentiation of TO cells is likely controlled by certain dendritic cells which promote IL-10 production and may express tolerogenic costimulatory molecules. Another subset of CD4+ Tr cells is defined by constitutive expression of CD25, and although these CD4+CD25+ Tr cells appear to suppress via mechanisms which are largely independent of cytokines, they may actively promote the differentiation of Tr1 cells. Many questions about the basic biology of Tr1 cells remain to be answered, but the development of therapeutic strategies designed to harness their immunoregulatory effects can already be contemplated
HUMAN HEMATOPOIETIC-CELLS AND THYMIC EPITHELIAL-CELLS INDUCE TOLERANCE VIA DIFFERENT MECHANISMS IN THE SCID-HU MOUSE THYMUS
No full textTo study the role of thymic education on the development of the human T cell repertoire, SCID-hu mice were constructed with fetal liver and fetal thymus obtained from the same or two different donors. These animals were studied between 7 and 12 mo after transplantation, at which times all thymocytes and peripheral T cells were derived from stem cells of the fetal liver graft. Immunohistology of the thymus grafts demonstrated that thymic epithelial cells were of fetal thymus donor (FTD) origin. Dendritic cells and macrophages of fetal liver donor (FLD) origin were abundantly present in the medullary and cortico-medullary areas. Thymocytes of SCID-hu mice transplanted with liver and thymus of two different donors (FLD(A)/FTD(B) animals) were nonresponsive to Epstein-Barr virus-transformed B cell lines (B-LCL) established from both the FLD(A) and FTD(B), but proliferated vigorously when stimulated with third-party allogeneic B-LCL. Mixing experiments showed that the nonresponsiveness to FTD(B) was not due to suppression. Limiting dilution analysis revealed that T cells reacting with the human histocompatibility leukocyte antigens (HLA) of the FLD were undetectable in the CD8+ T cell population and barely measurable in the CD4+ subset. On the other hand, CD4+ and CD8+ T cells reactive to the HLA antigens of the FTD were readily detectable. These results indicate that FLD-reactive cells were clonally deleted, whereas FTD-reactive cells were not. However, the frequencies of FTD-reactive T cells were consistently twofold lower than those of T cells specific for any third-party B-LCL. In addition, the cytotoxic activity and interleukin 2 production by FTD-specific T cells were lower compared with that of third-party-reactive T cell clones, suggesting that FTD-specific cells are anergic. These data demonstrate that T cells become tolerant to autologous and allogeneic HLA antigens expressed in the thymus via two different mechanisms: hematopoietic cells present in the thymus induce tolerance to "self"-antigens by clonal deletion, whereas thymic epithelial cells induce tolerance by clonal anergy and possibly deletion of high affinity clones
Methods for in vitro generation of human type 1 regulatory T cells
No full textType 1 regulatory T (Tr1) cells are adaptive regulatory T cells that are induced in the periphery upon chronic exposure to antigen (Ag) in a tolerogenic environment containing interleukin (IL)-10. Tr1 cells are Ag-specific; they produce high levels of IL-10 and TGF-β in the absence of IL-4 and suppress T-cell responses via a cytokine-dependent mechanism. During the last decade, several protocols have been developed to generate Tr1 cell lines in vitro. In this chapter, we outline protocols to generate non-Ag- and Ag-specific Tr1 cell lines and assays used to characterize Tr1 cell phenotype and functions
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