1,113 research outputs found

    To Ki or Not to Ki: Re-Evaluating the Use and Potentials of Ki-67 for T Cell Analysis

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    This study discusses substantive advances in T cell proliferation analysis, with the aim to provoke a re-evaluation of the generally-held view that Ki-67 is a reliable proliferation marker per se, and to offer a more sensitive and effective method for T cell cycle analysis, with informative examples in mouse and human settings. We summarize recent experimental work from our labs showing that, by Ki-67/DNA dual staining and refined flow cytometric methods, we were able to identify T cells in the S-G2/M phases of the cell-cycle in the peripheral blood (collectively termed “T Double S” for T cells in S-phase in Sanguine: in short “TDS” cells). Without our refinement, such cells may be excluded from conventional lymphocyte analyses. Specifically, we analyzed clonal expansion of antigen-specific CD8 T cells in vaccinated mice, and demonstrated the potential of TDS cells to reflect immune dynamics in human blood samples from healthy donors, and patients with type 1 diabetes, infectious mononucleosis, and COVID-19. The Ki-67/DNA dual staining, or TDS assay, provides a reliable approach by which human peripheral blood can be used to reflect the dynamics of human lymphocytes, rather than providing mere steady-state phenotypic snapshots. The method does not require highly sophisticated “-omics” capabilities, so it should be widely-applicable to health care in diverse settings. Furthermore, our results argue that the TDS assay can provide a window on immune dynamics in extra-lymphoid tissues, a long-sought potential of peripheral blood monitoring, for example in relation to organ-specific autoimmune diseases and infections, and cancer immunotherapy

    Electrochemical-control of abrasive polishing and machining rates, U.S. Patent 6,171,467

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    An apparatus and method is disclosed; both of which use electrochemistry to selectively grow and remove hard oxide coatings on metals, and capacitive double layers on non-metals and semiconductors in order to predict and control the rate of surface abrasion during planarization of the surface of such materials

    γδ T Cells and the Lymphoid Stress-Surveillance Response

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    The investigation of γδ T cells has identified a rapid lymphoid stress-surveillance response to microbial and nonmicrobial tissue perturbation. In addition to providing local protection, this response provides an immediate source of cytokines, chemokines, and other functions that can substantially affect downstream, adaptive immunity. Recent studies have identified striking mechanisms by which γδ cells meet the requirements of stress surveillance. For example, high response frequencies can reflect a unique nature of antigen engagement by the T cell receptor (TCR), developmental focusing of the repertoire by selection events, or the use of nonclonotypic receptors to initiate responses. Likewise, rapid functional deployment can be facilitated by the preprogramming of γδ cells during development. Additionally, γδ cells can directly influence adaptive immunity by functioning as antigen-presenting cells. With lymphoid stress surveillance likely to underpin numerous aspects of inflammation, tumor immunology, infectious disease, and autoimmunity, this perspective considers its properties and its emerging potential for clinical manipulation

    Retracted article: Students' learning styles and academic performance in Readings in Philippine History: Basis for a proposed course syllabus enhancement

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    The article entitled “Students’ learning styles and academic performance in Readings in Philippine History: Basis for a proposed course syllabus enhancement” (Volume 4, Issue 1, December 2022, pp. 45-51) written by Adrian Ote, Margie M. Lepangge, Nobelen Joy M. Marsonia, Sheena Joy C. Pagran, Jennilyn C. Se, and Jason A. Romero has been retracted at the request of the Corresponding Author

    Skint-1 Identifies a Common Molecular Mechanism for the Development of Interferon-γ-Secreting versus Interleukin-17-Secreting γδ T Cells

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    SummaryMurine T cell development begins with the generation of a unique Vγ5+Vδ1+ epidermal γδ T cell compartment and a unique, more broadly distributed Vγ6+Vδ1+ subset that is an important source of interleukin-17 (IL-17). This study showed that these respective functional programs were determined by Skint-1, a thymic epithelial cell determinant. By engaging Skint-1+ cells, Vγ5+Vδ1+ thymocytes induced an Egr3-mediated pathway, provoking differentiation and the potential to produce IFN-γ while suppressing the γδ T cell lineage factor, Sox13, and a RORγt transcription factor-associated IL-17-producing capacity. Hence, the functions of the earliest T cells are substantially preprogrammed in the thymus. Additionally, the phenotype of Skint-1-selected fetal thymocytes permitted identification in the adult thymus of an analogous gene regulatory network regulated by the γδ T cell receptor. Hence, these observations describe a molecular pathway by which distinct stress-responsive lymphocyte repertoires may emerge throughout ontogeny and offer parallels with emerging perspectives on the functional selection of other lymphoid cells

    Heavy-metal modulation of the human intercellular adhesion molecule (ICAM-1) gene expression

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    The intercellular adhesion molecule 1 (ICAM-1) can be induced on many different cell types by a set of various modulators (IL1 beta, TNF, LPS, IFN-gamma), which are released during the inflammatory process. We have investigated the possibility that other factors, related to the stress and biophysical perturbations of the inflammatory response, may also modulate ICAM-1. Here, we report that heavy metals, in particular zinc, can enhance the expression of the ICAM-1 gene on cells actively involved at different levels during inflammation. Kinetic studies of ICAM-1 gene expression shows a maximum level of induction 4 h after treatment with metals, followed by a rapid decrease to basal levels within 12 h. The effect on enhanced gene expression is mostly due to a rapid increase of the transcriptional rate as shown by nuclear run-on experiments. In B lymphoblastoid cells, but not in fibroblasts, the increase in RNA expression seems significantly greater that the subsequent increase in protein expression, suggesting that a further point of post-transcriptional regulation of ICAM-1 occurs and may be linked to the cellular specificity. may be linked to the cellular specificity

    Transcriptional modulation of the human intercellular adhesion molecule gene I (ICAM-1) by retinoic acid in melanoma cells

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    Retinoids play an important role as differentiating agents in a variety of normal and neoplastic cells and have been reported to induce ICAM-1 levels in melanomas, a phenomenon that we confirm in this paper, The effects of retinoids on gene expression usually involve the binding of specific retinoic acid receptor trans-acting factors (RARs) with their ligands, which then interact with specific target sites, the retinoic acid responsive elements (RAREs) present in the promoters of responsive genes, In the case of ICAM-1, we have cloned and analyzed the proximal regulatory region of the human gene, We show that the ICAM-1 promoter is RA-inducible, that it contains a putative consensus RARE (GGGTCATCGCCCTGCC), which binds in vitro RAR alpha complemented with RXRs, and that mutation of the RARE abrogates promoter responsiveness to RA, These studies allow ICAM-1 to be added to the list of genes transcriptionally activated by RA acting through an RARE element. (C) 1995 Academic Press,Inc

    γδ T cell update:Adaptate orchestrators of immune surveillance

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    As interest in γδ T cells grows rapidly, what key points are emerging, and where is caution warranted? γδ T cells fulfill critical functions, as reflected in associations with vaccine responsiveness and cancer survival in humans and ever more phenotypes of γδ T cell-deficient mice, including basic physiological deficiencies. Such phenotypes reflect activities of distinct γδ T cell subsets, whose origins offer interesting insights into lymphocyte development but whose variable evolutionary conservation can obfuscate translation of knowledge from mice to humans. By contrast, an emerging and conserved feature of γδ T cells is their "adaptate" biology: an integration of adaptive clonally-restricted specificities, innate tissue-sensing, and unconventional recall responses that collectively strengthen host resistance to myriad challenges. Central to adaptate biology are butyrophilins and other γδ cell regulators, the study of which should greatly enhance our understanding of tissue immunogenicity and immunosurveillance and guide intensifying clinical interest in γδ cells and other unconventional lymphocytes.</p
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