WorldWideScience

Sample records for cell subset involved

  1. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling.

    Science.gov (United States)

    Eyerich, Stefanie; Eyerich, Kilian; Pennino, Davide; Carbone, Teresa; Nasorri, Francesca; Pallotta, Sabatino; Cianfarani, Francesca; Odorisio, Teresa; Traidl-Hoffmann, Claudia; Behrendt, Heidrun; Durham, Stephen R; Schmidt-Weber, Carsten B; Cavani, Andrea

    2009-12-01

    Th subsets are defined according to their production of lineage-indicating cytokines and functions. In this study, we have identified a subset of human Th cells that infiltrates the epidermis in individuals with inflammatory skin disorders and is characterized by the secretion of IL-22 and TNF-alpha, but not IFN-gamma, IL-4, or IL-17. In analogy to the Th17 subset, cells with this cytokine profile have been named the Th22 subset. Th22 clones derived from patients with psoriasis were stable in culture and exhibited a transcriptome profile clearly separate from those of Th1, Th2, and Th17 cells; it included genes encoding proteins involved in tissue remodeling, such as FGFs, and chemokines involved in angiogenesis and fibrosis. Primary human keratinocytes exposed to Th22 supernatants expressed a transcriptome response profile that included genes involved in innate immune pathways and the induction and modulation of adaptive immunity. These proinflammatory Th22 responses were synergistically dependent on IL-22 and TNF-alpha. Furthermore, Th22 supernatants enhanced wound healing in an in vitro injury model, which was exclusively dependent on IL-22. In conclusion, the human Th22 subset may represent a separate T cell subset with a distinct identity with respect to gene expression and function, present within the epidermal layer in inflammatory skin diseases. Future strategies directed against the Th22 subset may be of value in chronic inflammatory skin disorders.

  2. B cell subsets in atherosclerosis

    Directory of Open Access Journals (Sweden)

    Heather M. Perry

    2012-12-01

    Full Text Available Atherosclerosis, the underlying cause of heart attacks and strokes, is a chronic inflammatory disease of the artery wall. Immune cells, including lymphocytes modulate atherosclerotic lesion development through interconnected mechanisms. Elegant studies over the past decades have begun to unravel a role for B cells in atherosclerosis. Recent findings provide evidence that B cell effects on atherosclerosis may be subset-dependent. B-1a B cells have been reported to protect from atherosclerosis by secretion of natural IgM antibodies. Conventional B-2 B cells can promote atherosclerosis through less clearly defined mechanism that may involve CD4 T cells. Yet, there may be other populations of B cells within these subsets with different phenotypes altering their impact on atherosclerosis. Additionally, the role of B cell subsets in atherosclerosis may depend on their environmental niche and/or the stage of atherogenesis. This review will highlight key findings in the evolving field of B cells and atherosclerosis and touch on the potential and importance of translating these findings to human disease.

  3. Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56bright subset

    Science.gov (United States)

    Mantegani, Paola; Tambussi, Giuseppe; Galli, Laura; Din, Chiara Tassan; Lazzarin, Adriano; Fortis, Claudio

    2010-01-01

    We investigated the distribution of natural killer (NK) cell subsets, their activating and inhibitory receptors, and their cytolytic potential, in primary human immunodeficiency virus (HIV)-infected (PHI) individuals at baseline and during 1 year of follow-up with or without antiretroviral therapy, and compared the results with those obtained in treatment-naïve, chronically HIV-infected (CHI) individuals, and HIV-seronegative (HN) healthy individuals. The proportion of the CD56dim and CD56bright subsets decreased with disease progression, whereas that of the CD56− CD16+ subset increased. In the CD56dim subset, the proportion of cells with natural cytotoxicity receptors (NCRs) decreased with disease progression, and their cytolytic potential was reduced. Conversely, the CD56bright subset was characterized by a high proportion of NCR-positive, killer cell immunoglobulin-like receptor (KIR)-positive NKG2A+ cells in both CHI and PHI individuals, which was associated with an increase in their cytolytic potential. During the 1 year of follow-up, the PHI individuals with high viraemia levels and low CD4+ T-cell counts who received highly active antiretroviral therapy (HAART) had a similar proportion of NK subsets to CHI individuals, while patients with low viraemia levels and high CD4+ T-cell counts who remained untreated had values similar to those of the HN individuals. Our results indicate a marked perturbation of the NK cell compartment during HIV-1 infection that is multifaceted, starts early and is progressive, primarily involves the CD56bright subset, and is partially corrected by effective HAART. PMID:19824914

  4. Identification of Suitable Reference Genes for Peripheral Blood Mononuclear Cell Subset Studies in Multiple Sclerosis

    DEFF Research Database (Denmark)

    Oturai, D B; Søndergaard, H B; Börnsen, L;

    2016-01-01

    Quantitative real-time PCR (qPCR) involves the need of a proper standard for normalizing the gene expression data. Different studies have shown the validity of reference genes to vary greatly depending on tissue, cell subsets and experimental context. This study aimed at the identification...... of suitable reference genes for qPCR studies using different peripheral blood cell subsets (whole blood (WB) cells, peripheral blood mononuclear cells (PBMCs) and PBMC subsets (CD4(+) T cells, CD8(+) T cells, NK cells, monocytes, B cells and dendritic cells) from healthy controls (HC), patients with relapsing...... stable combination for analyses of cell subsets between HC and RRMS patients, while the combination of UBC and YWHAZ was superior for analysis of cell subsets between HC, RRMS and RRMS-IFN-β groups. GAPDH was generally unsuitable for blood cell subset studies in multiple sclerosis. In conclusion, we...

  5. T Helper Cell Subsets in Clinical Manifestations of Psoriasis

    Directory of Open Access Journals (Sweden)

    Marco Diani

    2016-01-01

    Full Text Available Psoriasis is a chronic inflammatory skin disease, which is associated with systemic inflammation and comorbidities, such as psoriatic arthritis and cardiovascular diseases. The autoimmune nature of psoriasis has been established only recently, conferring a central role to epidermal CD8 T cells recognizing self-epitopes in the initial phase of the disease. Different subsets of helper cells have also been reported as key players in the psoriasis pathogenesis. Here, we reviewed the knowledge on the role of each subset in the psoriatic cascade and in the different clinical manifestations of the disease. We will discuss the role of Th1 and Th17 cells in the initiation and in the amplification phase of cutaneous inflammation. Moreover, we will discuss the recently proposed role of tissue resident Th22 cells in disease memory in sites of recurrent psoriasis and the possible involvement of Th9 cells. Finally, we will discuss the hypothesis of a link between T helper cell subsets recirculating from the skin and the systemic manifestations of psoriasis.

  6. T Helper Cell Subsets in Clinical Manifestations of Psoriasis

    Science.gov (United States)

    Diani, Marco; Altomare, Gianfranco

    2016-01-01

    Psoriasis is a chronic inflammatory skin disease, which is associated with systemic inflammation and comorbidities, such as psoriatic arthritis and cardiovascular diseases. The autoimmune nature of psoriasis has been established only recently, conferring a central role to epidermal CD8 T cells recognizing self-epitopes in the initial phase of the disease. Different subsets of helper cells have also been reported as key players in the psoriasis pathogenesis. Here, we reviewed the knowledge on the role of each subset in the psoriatic cascade and in the different clinical manifestations of the disease. We will discuss the role of Th1 and Th17 cells in the initiation and in the amplification phase of cutaneous inflammation. Moreover, we will discuss the recently proposed role of tissue resident Th22 cells in disease memory in sites of recurrent psoriasis and the possible involvement of Th9 cells. Finally, we will discuss the hypothesis of a link between T helper cell subsets recirculating from the skin and the systemic manifestations of psoriasis. PMID:27595115

  7. A novel cell subset:Interferon-producing killer dendritic cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Recent reports introduce a novel cell subset of DCs with antigenic phenotypes shared by both NK cells and B cells, but without surface markers of pDCs and T cells, appearing to be a chimera of NK cells and DCs, namely interferon-producing killer dendritic cells(IKDCs).IKDCs not only secret type I and type II interferons to recognize and kill tumor cells effectively, but also express MHC-II molecules to present antigens.Thus, IKDCs are considered as important immunosurveilance cells for tumors, providing a link between innate and adaptive immunity.

  8. Neurohypophysial Receptor Gene Expression by Thymic T Cell Subsets and Thymic T Cell Lymphoma Cell Lines

    Directory of Open Access Journals (Sweden)

    I. Hansenne

    2004-01-01

    transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors belong to the G protein-linked seven-transmembrane receptor superfamily and are encoded by four distinct genes, OTR, V1R, V2R and V3R. The objective of this study was to identify the nature of neurohypophysial receptor in thymic T cell subsets purified by immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP and BW5147. OTR is transcribed in all thymic T cell subsets and T cell lines, while V3R transcription is restricted to CD4+ CD8+ and CD8+ thymic cells. Neither V1R nor V2R transcripts are detected in any kind of T cells. The OTR protein was identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6 mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not modify the percentage of T cell subsets, but increases late T cell apoptosis further evidencing the involvement of OT/OTR signaling in the control of T cell proliferation and survival. According to these data, OTR and V3R are differentially expressed during T cell ontogeny. Moreover, the restriction of OTR transcription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment.

  9. Origin of CD8+ Effector and Memory T Cell Subsets

    Institute of Scientific and Technical Information of China (English)

    Christian Stemberger; Michael Neuenhahn; Veit R.Buchholz; Dirk H.Busch

    2007-01-01

    It is well accepted that CD8+ T cells play a pivotal role in providing protection against infection with intracellular pathogens and some tumors. In many cases protective immunity is maintained for long periods of time (immunological memory). Over the past years, it has become evident that in order to fulfill these multiple tasks,distinct subsets of effector and memory T cells have to be generated. Until today, however, little is known about the underlying mechanisms of subset differentiation and the timing of lineage fate decisions. In this context, it is of special importance to determine at which level of clonal expansion functional and phenotypical heterogeneity is achieved. Different models for T cell subset diversification have been proposed; these differ mainly in the time point during priming and clonal expansion (prior, during, or beyond the first cell division) when differentiation programs are induced. Recently developed single-cell adoptive transfer technology has allowed us to demonstrate that individual precursor cell still bears the full plasticity to develop into a plethora different T cell subsets. This observation targets the shaping of T cell subset differentiation towards factors that are still operative beyond the first cell division. These findings have important implications for vaccine development, as the modulation of differentiation patterns towards distinct subsets could become a powerful strategy to enhance the efficacy and quality of vaccines.

  10. Investigating evolutionary conservation of dendritic cell subset identity and functions

    Directory of Open Access Journals (Sweden)

    Thien-Phong eVu Manh

    2015-06-01

    Full Text Available Dendritic cells (DC were initially defined as mononuclear phagocytes with a dendritic morphology and an exquisite efficiency for naïve T cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to excel in distinct functions and to develop under the instruction of different transcription factors or cytokines. Very few cell surface molecules are expressed in a specific manner on any immune cell type. Hence, to identify cell types, the sole use of a small number of cell surface markers in classical flow cytometry can be deceiving. Moreover, the markers currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of DC subset identity and in their attribution of specific functions. There is a strong need to identify a rigorous and consensus way to define mononuclear phagocyte subsets, with precise guidelines potentially applicable throughout tissues and species. We will discuss the advantages, drawbacks and complementarities of different methodologies: cell surface phenotyping, ontogeny, functional characterization and molecular profiling. We will advocate that gene expression profiling is a very rigorous, largely unbiased and accessible method to define the identity of mononuclear phagocyte subsets, which strengthens and refines surface phenotyping. It is uniquely powerful to yield new, experimentally testable, hypotheses on the ontogeny or functions of mononuclear phagocyte subsets, their molecular regulation and their evolutionary conservation. We propose defining cell populations based on a combination of cell surface phenotyping, expression analysis of hallmark genes and robust functional assays, in order to reach a consensus and integrate faster the huge but scattered knowledge accumulated by different laboratories on different cell types

  11. T-cell subsets in the germinal center.

    Science.gov (United States)

    Ramiscal, Roybel R; Vinuesa, Carola G

    2013-03-01

    T cells are known to migrate to B-cell-enriched follicles and germinal centers within secondary lymphoid organs to provide help to B cells. Cognate T:B interactions that take place at the T:B border and subsequently within germinal centers are essential for B-cell priming, differentiation into germinal center B cells, and selection of mutated cells into memory B cells or memory plasma cells. In recent years, different stages of maturation within B-cell helper T cells, collectively known as B-follicular helper T (Tfh) cells, as well as heterogeneity amid germinal center T cells are becoming clear. Indeed, germinal centers support not only bona fide Tfh cells but also CD4(+) and CD8(+) follicular regulatory T (Tfr) cells that act to suppress germinal center responses and B-cell helper natural killer T cells. There is a growing need for more precise phenotypic and functional distinction of these specialized T-cell subsets. In this review, we summarize current knowledge on the ontogeny, molecular identity, and functional relevance of the various subsets of germinal center T cells.

  12. Activin signal promotes cancer progression and is involved in cachexia in a subset of pancreatic cancer.

    Science.gov (United States)

    Togashi, Yosuke; Kogita, Akihiro; Sakamoto, Hiroki; Hayashi, Hidetoshi; Terashima, Masato; de Velasco, Marco A; Sakai, Kazuko; Fujita, Yoshihiko; Tomida, Shuta; Kitano, Masayuki; Okuno, Kiyotaka; Kudo, Masatoshi; Nishio, Kazuto

    2015-01-28

    We previously reported that activin produces a signal with a tumor suppressive role in pancreatic cancer (PC). Here, the association between plasma activin A and survival in patients with advanced PC was investigated. Contrary to our expectations, however, patients with high plasma activin A levels had a significantly shorter survival period than those with low levels (median survival, 314 days vs. 482 days, P = 0.034). The cellular growth of the MIA PaCa-2 cell line was greatly enhanced by activin A via non-SMAD pathways. The cellular growth and colony formation of an INHBA (beta subunit of inhibin)-overexpressed cell line were also enhanced. In a xenograft study, INHBA-overexpressed cells tended to result in a larger tumor volume, compared with a control. The bodyweights of mice inoculated with INHBA-overexpressed cells decreased dramatically, and these mice all died at an early stage, suggesting the occurrence of activin-induced cachexia. Our findings indicated that the activin signal can promote cancer progression in a subset of PC and might be involved in cachexia. The activin signal might be a novel target for the treatment of PC.

  13. CD163 positive subsets of blood dendritic cells

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh

    2006-01-01

    expression in dendritic cells (DCs) was investigated using multicolor flow cytometry in peripheral blood from 31 healthy donors and 15 HIV-1 patients in addition to umbilical cord blood from 5 newborn infants. Total RNA was isolated from MACS purified DCs and CD163 mRNA was determined with real-time reverse...... transcriptase polymerase chain reaction. The effect of glucocorticoid and phorbol ester stimulation on monocyte and dendritic cell CD163 and CD91 expression was investigated in cell culture of mononuclear cells using multicolor flow cytometry. We identified two CD163+ subsets in human blood with dendritic cell...

  14. Myeloid-derived suppressor cell heterogeneity and subset definition.

    Science.gov (United States)

    Peranzoni, Elisa; Zilio, Serena; Marigo, Ilaria; Dolcetti, Luigi; Zanovello, Paola; Mandruzzato, Susanna; Bronte, Vincenzo

    2010-04-01

    Myeloid derived suppressor cells (MDSCs) are defined in mice on the basis of CD11b and Gr-1 marker expression and the functional ability to inhibit T lymphocyte activation. Nevertheless the term 'heterogeneous' remains the first, informal feature commonly attributed to this population. It is clear that CD11b(+)Gr-1(+) cells are part of a myeloid macropopulation, which comprises at least two subsets of polymorphonuclear and monocytic cells with different immunosuppressive properties. While recent literature shows substantial agreement on the immunoregulatory property of the monocytic MDSC subset, there is still contrasting evidence on the role of the granulocytic fraction. Moreover, this dichotomy holds true for human MDSCs. We attempt here to summarize conflicting findings in the field and provide some possible, unifying explanations.

  15. Cytokine-producing T cell subsets in human leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, Kåre

    2000-01-01

    Leishmania specific Th1/Th2 cells have been identified in humans as well as in mice. There is a correlation between the clinical outcome of the infection and the cytokine response profile. Generally, the production of Th2 cytokines leads to severe infection, whereas the production of Th1 cytokine...... cells mutually down-regulate each other. However, the presence of antigen specific regulatory T cell subsets may provide an environment that allows the presence of both Th1 and Th2 cells....

  16. Immunity to pathogens taught by specialized human dendritic cell subsets.

    Directory of Open Access Journals (Sweden)

    Jens A. E. Geginat

    2015-10-01

    Full Text Available Dendritic cells (DC are specialized antigen-presenting cells (APC that have a key role in immune responses, because they bridge the innate and adaptive arms of the immune system. They mature upon recognition of pathogens and up-regulate MHC molecules and co-stimulatory receptors to activate antigen-specific CD4+ and CD8+ T-cells. It is now well established that DC are not a homogeneous population, but are composed of different subsets with specialized functions in immune responses to specific pathogens. Upon viral infections, plasmacytoid DC (pDC rapidly produce large amounts of IFN-α, which has potent anti-viral functions and activates several other immune cells. However, pDC are not particularly potent APC and induce the tolerogenic cytokine IL-10 in CD4+ T-cells. In contrast, myeloid DC (mDC are very potent APC and possess the unique capacity to prime naïve T-cells and consequently to initiate a primary adaptive immune response. Different subsets of myeloid DC with specialized functions have been identified. In mice, CD8α+ mDC capture antigenic material from necrotic cells, secrete high levels of IL-12, and prime Th1 and cytotoxic T cell responses to control intracellular pathogens. Conversely, CD8α- mDC preferentially prime CD4+ T-cells and promote Th2 or Th17 differentiation. BDCA-3+ mDC2 are the human homologue of CD8α+ mDC, since they share the expression of several key molecules, the capacity to cross-present antigens to CD8+ T-cells and to produce IFN-λ. However, although several features of the DC network are conserved between humans and mice, the expression of several relevant toll-like receptors as well as the production of cytokines that regulate T-cell differentiation are different. Intriguingly, recent data suggests specific roles for human DC subsets in immune responses against individual pathogens. The biology of human DC subsets holds the promise to be exploitable in translational medicine, in particular for the

  17. Plasticity of T helper cell subsets: Implications in periodontal disease

    Directory of Open Access Journals (Sweden)

    Avaneendra Talwar

    2013-01-01

    Full Text Available T helper (Th cells have an important role in host defence as well in the pathogenesis of periodontal disease. Th cells differentiate from naive cells into various subsets, each of which is associated with a set of inducing and effector cytokines. Previously, it was thought that this differentiation was an irreversible event. Recent evidence suggest that even differentiated Th cells, retain the flexibility to transform from one lineage to another, a phenomenon referred to as plasticity. This plasticity is thought to be brought about by epigenetic modifications that are regulated by external and internal signals in the micro-environment of these cells. The factors and mechanisms which affect the plasticity of these cells and their potential role in the etio-pathogenesis of periodontal disease has been described in this article.

  18. Plasma cell alloantigen ENPP1 is expressed by a subset of human B cells with potential regulatory functions.

    Science.gov (United States)

    Yoon, Jeongheon; Wang, Hongsheng; Kim, Yong Chan; Yoshimoto, Momoko; Abbasi, Sadia; Morse Iii, Herbert C

    2016-09-01

    Plasma cell alloantigen 1 (PC1), also known as ENPP1 (ectonucleotide pyrophosphatase/phosphodiesterase 1), is an enzyme involved primarily in hydrolysis of adenosine triphosphate at the cell surface. Although the expression pattern of PC1 is relatively broad, its expression in B cells is found at significant levels only in terminally differentiated germinal center B cells, plasma cells and a subset of B-1a cells in mice. Here we describe studies designed to determine whether expression of PC1 might define novel populations of human B cells with similarities to mouse B cells. We found that PC1 is expressed in small populations of human B lineage cells in peripheral blood, cord blood, tonsils, bone marrow and pediatric peritoneal fluid, with the highest levels in plasma cells. The characteristics of human PC1(+) B cells differ from mouse peritoneal B-1a subsets and from features of the human CD20(+)CD27(+)CD43(+)CD70(-) B-cell subset proposed to be human B-1 cells. Expression of PC1 was greatly increased in B cells stimulated with the combination of CD40 ligand, interleukin (IL)-4 and IL-21. In addition, PC1(+) B cells activated CD4(+) T regulatory cells. ENPP1 thus defines a subset of human B cells that differs significantly from mouse peritoneal B-1a and proposed human B-1 cells.

  19. Mast cell subsets and neuropeptides in leprosy reactions

    Directory of Open Access Journals (Sweden)

    Antunes Sérgio Luiz Gomes

    2003-01-01

    Full Text Available The immunohistochemical identification of neuropeptides (calcitonin gene-related peptide, vasoactive intestinal polypeptide, substance P, alpha-melanocyte stimulating hormone and gamma-melanocyte stimulating hormone quantification of mast cells and their subsets (tryptase/chymase-immunoreactive mast cells = TCMC and tryptase-immunoreactive mast cells = TMC were determined in biopsies of six patients with leprosy reactions (three patients with type I reaction and three with type II. Biopsies were compared with those taken from the same body site in the remission stage of the same patient. We found a relative increase of TMC in the inflammatory infiltrate of the reactional biopsies compared to the post-reactional biopsy. Also, the total number of mast cells and the TMC/TCMC ratio in the inflammatory infiltrate was significantly higher than in the intervening dermis of the biopsies of both periods. No significant difference was found regarding neuroptide expression in the reactional and post-reactional biopsies. The relative increase of TMC in the reactional infiltrates could implicate this mast cell subset in the reported increase of the immune response in leprosy reactions.

  20. Dysregulation of CD4(+) T Cell Subsets in Intracranial Aneurysm.

    Science.gov (United States)

    Zhang, Hai-Feng; Zhao, Ming-Guang; Liang, Guo-Biao; Yu, Chun-Yong; He, Wenxiu; Li, Zhi-Qing; Gao, Xu

    2016-02-01

    Intracranial aneurysms (IAs) and potential IA rupture are one of the direct causes of permanent brain damage and mortality. Interestingly, the major risk factors of IA development, including hemodynamic stress, hypertension, smoking, and genetic predispositions, are closely associated with a proinflammatory immune status. Therefore, we examined the roles of CD4(+) T cells in IA pathogenesis. IA patients exhibited peripheral CD4(+) T-cell imbalance, with overrepresented T helper 1 (Th1) and Th17 activities and underrepresented Th2 and regulatory T (Treg) activities, including increased IFN-γ, TNF-α, and IL-17 production and decreased IL-10 production from total CD4(+) T cells. Chemokine receptors CXCR3 and CCR6 were used to identify Th1, Th2, and Th17 cell subsets, and CD4(+)CD25(hi) was used to identify Treg cells. Based on these markers, the data then showed altered cytokine production by each cell type and shifted subpopulation frequency. Moreover, this shift in frequency was directly correlated with IA severity. To examine the underlying mechanism of CD4(+) T cell skewing, we cocultured CD4(+) T cells with autologous monocytes and found that coculture with monocytes could significantly increase IFN-γ and IL-17 production through contact-independent mechanisms, demonstrating that monocytes could potentially contribute to the altered CD4(+) T cell composition in IA. Analyzing mRNA transcripts revealed significantly upregulated IL-1β and TNF-α expression by monocytes from IA patients. We found a loss of CD4(+) T cell subset balance that was likely to promote a higher state of inflammation in IA, which may exacerbate the disease through a positive feedback loop.

  1. NK cell subset redistribution during the course of viral infections

    Directory of Open Access Journals (Sweden)

    Enrico eLugli

    2014-08-01

    Full Text Available Natural killer (NK cells are important effectors of innate immunity that play a critical role in the control of human viral infections. Indeed, given their capability to directly recognize virally infected cells without the need of specific antigen presentation, NK cells are on the first line of defense against these invading pathogens. By establishing cellular networks with a variety of cell types such as dendritic cells, NK cells can also amplify anti-viral adaptive immune responses. In turn, viruses evolved and developed several mechanisms to evade NK cell-mediated immune activity. It has been reported that certain viral diseases, including human immunodeficiency virus-1 (HIV-1 as well as cytomegalovirus (CMV infections, are associated with a pathologic redistribution of NK cell subsets in the peripheral blood. In particular, it has been observed the expansion of unconventional CD56neg NK cells, whose effector functions are significantly impaired as compared to that of conventional CD56pos NK cells. In this review, we address the impact of chronic viral infections on the functional and phenotypic perturbations of human NK cell compartment.

  2. Immunophenotype of normal and myelomatous plasma cell subsets

    Directory of Open Access Journals (Sweden)

    Nelly eRobillard

    2014-03-01

    Full Text Available Plasma-cells are essentially characterized by the co-expression of CD138 and CD38, which allows their identification in flow cytometry in bone marrow, peripheral blood or cell suspensions from tissues. These terminally differentiated B-cells may lose the expression of surface CD19 and that of CD20 while retaining CD27. When malignant, they can gain a number of other markers such as CD28, CD33, CD56 or CD117 and lose CD27. Moreover, since each plasma cell is only able to produce a single type of immunoglobulins, they display isotypic restriction and clonal malignant plasma cells can be further characterized by their homogeneous expression of either kappa or lambda light chains. In multiple myeloma (MM, such plasma cell clones produce the immunoglobulin identified in plasma as an abnormal peak. In the bone marrow where they essentially accumulate, these plasma cells may however display various immunophenotypes. The latter were explored in a two-way approach. Firstly the various subsets delineated by the selective or common expression of CD19 together with combined CD56/CD28 were explored in normal and MM bone marrow. Then other aberrant markers’ expression was investigated, i.e. CD20, CD27, CD33, CD56, CD117. These data were compared to literature information. They underline the vast heterogeneity of MM plasma cells possibly accounting for the various answers to therapy of MM patients.

  3. A Progenitor Cell Expressing Transcription Factor RORγt Generates All Human Innate Lymphoid Cell Subsets.

    Science.gov (United States)

    Scoville, Steven D; Mundy-Bosse, Bethany L; Zhang, Michael H; Chen, Li; Zhang, Xiaoli; Keller, Karen A; Hughes, Tiffany; Chen, Luxi; Cheng, Stephanie; Bergin, Stephen M; Mao, Hsiaoyin C; McClory, Susan; Yu, Jianhua; Carson, William E; Caligiuri, Michael A; Freud, Aharon G

    2016-05-17

    The current model of murine innate lymphoid cell (ILC) development holds that mouse ILCs are derived downstream of the common lymphoid progenitor through lineage-restricted progenitors. However, corresponding lineage-restricted progenitors in humans have yet to be discovered. Here we identified a progenitor population in human secondary lymphoid tissues (SLTs) that expressed the transcription factor RORγt and was unique in its ability to generate all known ILC subsets, including natural killer (NK) cells, but not other leukocyte populations. In contrast to murine fate-mapping data, which indicate that only ILC3s express Rorγt, these human progenitor cells as well as human peripheral blood NK cells and all mature ILC populations expressed RORγt. Thus, all human ILCs can be generated through an RORγt(+) developmental pathway from a common progenitor in SLTs. These findings help establish the developmental signals and pathways involved in human ILC development.

  4. mIL-2R, T cell subsets & hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Chao-Pin Li; Ke-Xia Wang; Jian Wang; Bo-Rong Pan

    2002-01-01

    AIM: To study the levels of membrane interleukin-2 receptor(mIL-2R ) and T cell subsets in peripheral bloodmononuclear cells (PBMC) from patients with hepatitis Cand their role in the pathogenesis of hepatitis C.METHODS: The levels of mlL-2R and T cells subsets in PBMCWere detected by biotin- streptstividin (BSA) technique beforeand after stimulation with PHA in 203 patients with hepatitis Cwith HCV-RNA( + ), anti-HCV( + ), anti-HCV(-).RESULTS: The total expressive levels of mlL-2R before andafter stimulation with PHA(0.03 ± 0.01, 0.03 ± 0.02, 0.04 ± 0.02, 0.36±0.03), and Tcell subsets in PBMC (0.62±0.06,0.37 ± 0.05, 0.35 ± 0.07) were all lower in patients withhepatitis C than those in normal controls (0.66 ± 0.07, 0.41± 0.06, 0.31 ± 0.05, P < 0.01 ). Among the patients, thelevels of mlL-2R were lower in silence than those in situationof PHA inducting (P< 0.01). However, the levels of mlL-2Rwere similar in acute hepatitis C to that in chronic hepatitis C(P>0.05). The levels of CD3+, CD4+, CD4 +/CD8+ Were lov erand CD8 + was higher in patients with acute and chronichepatitis C with anti-HCV( + ) than those in normal controls (0.62±0.06, 0.37±0.05, 0.35±0.07, 1.18±0.30, 0.61±0.07, 0.37±0.05, 1.39±0.33, 0.31±0.05, P<0.05-P<0.01).CONCLUSION: The cellular immunity is obviously changed inpatients with hepatitis C. The levels of mlL-2R end activationof T cells am closely associated with chronicity of hepatitis C.

  5. Value of the peripheral blood B-cells subsets in patients with ankylosing spondylitis

    Institute of Scientific and Technical Information of China (English)

    LIN Qu; GU Jie-ruo; LI Tian-wang; ZHANG Fu-cheng; LIN Zhi-ming; LIAO Ze-tao; WEI Qiu-jing; CAO Shuang-yan; LI Li

    2009-01-01

    Background The role of B-cell remains an enigma in the pathogenesis of ankylosing spondylitis(AS).This study aimed to investigate the distributions of B-cells and subsets in peripheral blood of AS patients and observe their changes in etanercept-treated AS patents.Methods We detected the proportions of CD19+ B-cell,naive B-cell(CD19+CD27),memory B-cell(CD19+CD27dim)and plasmablast(CD19+CD27high)in peripheral blood of 66 patients with AS(39 at active stage,27 at stable stage;35patients with peripheral joint involvement,31 patients with axial involvement alone),30 patients with rheumatoid arthritis (RA)and 30 healthy volunteers using flow cytometry.And then we observedthe changes of the above indexes of 39 active AS patients treated with etanercept in a randomized,double-blind,placebo-controlled trial.Results (1)Percentages of CD19+ B-cells in active or peripheral joint involvement AS patients increased more obviously than those in stable or axial involvement alone AS patients(both P=0.001),and percentage of CD19+CD27high B-cells in AS patients with peripheral joint involvement was significantly higher than that in cases with axial involvement alone or healthy volunteers(P=0.005 and 0.006,respectively);(2)The percentage of CD19+ B-cells in AS patients was positively correlated with Bath Ankylosing Spondylitis Disease Activity Index(BASDAI)scores,Patient's Global Assessment(PGA)scores,total back pain scores and nocturnal back pain scores(r=0.270,0.255,0.251 and 0.266,P=0.029,0.039,0.042 and 0.031,respectively);(3)At week 6 and week 12,there were no statistical differences of the percentages of B-cells and subsets between etanercept group and placebo group of AS patients(P>0.05);the percentage of CD19+ B-cells in etanercept group was higher than that in healthy volunteers at week 12(t=3.320,P=0.003).Conclusions Misbalance is present in B-cells and some subsets in peripheral blood of active AS patients with peripheral joint involved.B-cells might play an important

  6. Inflammation-Induced Changes in Circulating T-Cell Subsets and Cytokine Production During Human Endotoxemia

    DEFF Research Database (Denmark)

    Ronit, Andreas; Plovsing, Ronni R; Gaardbo, Julie C;

    2016-01-01

    -γ in response to phytohaemagglutinin but did not affect TLR4 expression on Tregs. No changes in the absolute count or frequency of BALF T cells were observed. Systemic inflammation is associated with lymphopenia, a relative increase in the frequency of anti-inflammatory Tregs, and a functional impairment of T......Observational clinical studies suggest the initial phase of sepsis may involve impaired cellular immunity. In the present study, we investigated temporal changes in T-cell subsets and T-cell cytokine production during human endotoxemia. Endotoxin (Escherichia coli lipopolysaccharide 4 ng...

  7. The cell biology of cross-presentation and the role of dendritic cell subsets.

    Science.gov (United States)

    Lin, Ming-Lee; Zhan, Yifan; Villadangos, Jose A; Lew, Andrew M

    2008-01-01

    The cell biology of cross-presentation is reviewed regarding exogenous antigen uptake, antigen degradation and entry into the major histocompatibility complex class I pathway. Whereas cross-presentation is not associated with enhanced phagocytic ability, certain receptors may favour uptake for cross-presentation for example mannose receptor for soluble glycoproteins. Perhaps, the defining property of the cross-presenting cell is some specialization in host machinery for handling and transport of antigen across organelles. Both cytosolic and vacuolar pathways are discussed. Which dendritic cell (DC) subset is the cross-presenting cell is explored. Cross-presentation is found within the CD8(+) subset resident in lymphoid organs. The role of other DC subsets (especially the migratory CD8(-) DC) and the route of antigen delivery are also discussed. Further consideration is given to antigen transfer between DC subsets and differential presentation to naive vs memory T cells.

  8. Phenotypic and functional distinctions between the TH2+ and JRA+ T cell subsets in man.

    Science.gov (United States)

    Reinherz, E L; Strelkauskas, A J; O'Brien, C; Schlossman, S F

    1979-07-01

    Prior work has demonstrated the existence of distinct human peripheral blood T cell subsets by utilizing heterologous as well as autoimmune antisera. In the present study, the relationship between the TH2+ and JRA+ T cell subsets was examined. T cells were purified with Sephadex G-200 anti-F(ab)2' affinity chromatography and E-rosetting technique, and subsequently fractionated into TH2+ and TH2- subsets by utilizing indirect immunofluorescence on FACS. Approximately 40 to 45% of the TH2- subset was shown to be JRA+, whereas less than 5% of the TH2+ subset was JRA+. In reciprocal studies, T cells were fractionated into JRA+ and JRA- subsets and reacted with heterologous antisera with anti-TH2+ specificity and indirect immunofluorescence. FACS analysis demonstrated that the JRA+ population contained no TH2+ T cells. In contrast, the JRA- population contained TH2+ T cells and accounted for the entire TH2+ subset found in the unfractionated T cell population. Functional studies showed that the TH2+ subset, and not the JRA+ subset, contain the effector population for cell-mediated lympholysis. It is concluded that the TH2+ and JRA+ T cell subsets define distinct and different T cell populations in man.

  9. Comparative expression profiling of distinct T cell subsets undergoing oxidative stress.

    Directory of Open Access Journals (Sweden)

    Rudolf Lichtenfels

    Full Text Available The clinical outcome of adoptive T cell transfer-based immunotherapies is often limited due to different escape mechanisms established by tumors in order to evade the hosts' immune system. The establishment of an immunosuppressive micromilieu by tumor cells along with distinct subsets of tumor-infiltrating lymphocytes is often associated with oxidative stress that can affect antigen-specific memory/effector cytotoxic T cells thereby substantially reducing their frequency and functional activation. Therefore, protection of tumor-reactive cytotoxic T lymphocytes from oxidative stress may enhance the anti-tumor-directed immune response. In order to better define the key pathways/proteins involved in the response to oxidative stress a comparative 2-DE-based proteome analysis of naïve CD45RA(+ and their memory/effector CD45RO(+ T cell counterparts in the presence and absence of low dose hydrogen peroxide (H(2O(2 was performed in this pilot study. Based on the profiling data of these T cell subpopulations under the various conditions, a series of differentially expressed spots were defined, members thereof identified by mass spectrometry and subsequently classified according to their cellular function and localization. Representative targets responding to oxidative stress including proteins involved in signaling pathways, in regulating the cellular redox status as well as in shaping/maintaining the structural cell integrity were independently verified at the transcript and protein level under the same conditions in both T cell subsets. In conclusion the resulting profiling data describe complex, oxidative stress-induced, but not strictly concordant changes within the respective expression profiles of CD45RA(+ and CD45RO(+ T cells. Some of the differentially expressed genes/proteins might be further exploited as potential targets toward modulating the redox capacity of the distinct lymphocyte subsets thereby providing the basis for further studies

  10. Holistic systems biology approaches to molecular mechanisms of human helper T cell differentiation to functionally distinct subsets.

    Science.gov (United States)

    Chen, Z; Lönnberg, T; Lahesmaa, R

    2013-08-01

    Current knowledge of helper T cell differentiation largely relies on data generated from mouse studies. To develop therapeutical strategies combating human diseases, understanding the molecular mechanisms how human naïve T cells differentiate to functionally distinct T helper (Th) subsets as well as studies on human differentiated Th cell subsets is particularly valuable. Systems biology approaches provide a holistic view of the processes of T helper differentiation, enable discovery of new factors and pathways involved and generation of new hypotheses to be tested to improve our understanding of human Th cell differentiation and immune-mediated diseases. Here, we summarize studies where high-throughput systems biology approaches have been exploited to human primary T cells. These studies reveal new factors and signalling pathways influencing T cell differentiation towards distinct subsets, important for immune regulation. Such information provides new insights into T cell biology and into targeting immune system for therapeutic interventions.

  11. Contributions of cell subsets to cytokine production during normal and impaired wound healing.

    Science.gov (United States)

    Mirza, Rita E; Koh, Timothy J

    2015-02-01

    The objective of this study was to determine the relative contributions of different cell subsets to the production of cytokines and growth factors during normal and impaired wound healing. Cells were isolated from wounds of non-diabetic and diabetic mice and separated by magnetic sorting into neutrophils/T cells/B cells (NTB cell subset), monocytes/macrophages (Mo/Mp subset) and non-leukocytic cells including keratinocyte/fibroblast/endothelial cells (KFE subset). On both per cell and total contribution bases, the Mo/Mp subset was the dominant producer of pro-inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-6 in both non-diabetic and diabetic mice and was a significant producer of vascular endothelial cell growth factor (VEGF)-A, insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β1. The NTB subset was also a significant producer of TNF-α and IL-10 whereas the KFE subset contributed significant amounts of VEGF, IGF-1 and TGF-β1. Sustained production of pro-inflammatory cytokines and impaired production of healing-associated factors were evident in each subset in diabetic mice. These data will be useful for further experimental and modeling studies on the role of cell subsets in wound healing as well as for designing therapeutic strategies for improving healing.

  12. Molecular mechanisms of differentiation of murine pro-inflammatory gamma-delta T cell subsets

    Directory of Open Access Journals (Sweden)

    Bruno eSilva-Santos

    2013-12-01

    Full Text Available Gamma-delta (gd T cells are unconventional innate-like lymphocytes that actively participate in protective immunity against tumors and infectious organisms including bacteria, viruses and parasites. However, gd T cells are also involved in the development of inflammatory and autoimmune diseases. gd T cells are functionally characterized by very rapid production of pro-inflammatory cytokines, while also impacting on (slower but long-lasting adaptive immune responses. This makes it crucial to understand the molecular mechanisms that regulate  T cell effector functions. Although they share many similarities with ab T cells, our knowledge of the molecular pathways that control effector functions in gd T cells still lags significantly behind. In this review, we focus on the segregation of interferon-gamma versus interleukin-17 production in murine thymic-derived gd T cell subsets defined by CD27 and CCR6 expression levels. We summarize the most recent studies that disclose the specific epigenetic and transcriptional mechanisms that govern the stability or plasticity of discrete pro-inflammatory gd T cell subsets, whose manipulation may be valuable for regulating (autoimmune responses.

  13. Differential Aspartate Usage Identifies a Subset of Cancer Cells Particularly Dependent on OGDH

    Directory of Open Access Journals (Sweden)

    Eric L. Allen

    2016-10-01

    Full Text Available Although aberrant metabolism in tumors has been well described, the identification of cancer subsets with particular metabolic vulnerabilities has remained challenging. Here, we conducted an siRNA screen focusing on enzymes involved in the tricarboxylic acid (TCA cycle and uncovered a striking range of cancer cell dependencies on OGDH, the E1 subunit of the alpha-ketoglutarate dehydrogenase complex. Using an integrative metabolomics approach, we identified differential aspartate utilization, via the malate-aspartate shuttle, as a predictor of whether OGDH is required for proliferation in 3D culture assays and for the growth of xenograft tumors. These findings highlight an anaplerotic role of aspartate and, more broadly, suggest that differential nutrient utilization patterns can identify subsets of cancers with distinct metabolic dependencies for potential pharmacological intervention.

  14. CLINICAL VALUE OF DETECTING T LYMPHOCYTE SUBSET AND NK CELL ACTIVITY IN PATIENTS WITH COLORECTAL CANCER

    Institute of Scientific and Technical Information of China (English)

    刘长安; 管增伟; 孙武; 邵玉霞; 李卓; 贾廷珍

    2001-01-01

    Objective To study on the expression and clinical significance of T lymphocyte subset and NK cell activity (NKA) in patients with colorectal cancer. Methods Fifty-seven cancer patients and 33 healthy controls were enrolled in this study. T lymphocyte subset was measured by SAP technique and NKA by LDH release assay based on K562 cells, which served as target cells.

  15. Innate-like functions of natural killer T cell subsets result from highly divergent gene programs.

    Science.gov (United States)

    Engel, Isaac; Seumois, Grégory; Chavez, Lukas; Samaniego-Castruita, Daniela; White, Brandie; Chawla, Ashu; Mock, Dennis; Vijayanand, Pandurangan; Kronenberg, Mitchell

    2016-06-01

    Natural killer T cells (NKT cells) have stimulatory or inhibitory effects on the immune response that can be attributed in part to the existence of functional subsets of NKT cells. These subsets have been characterized only on the basis of the differential expression of a few transcription factors and cell-surface molecules. Here we have analyzed purified populations of thymic NKT cell subsets at both the transcriptomic level and epigenomic level and by single-cell RNA sequencing. Our data indicated that despite their similar antigen specificity, the functional NKT cell subsets were highly divergent populations with many gene-expression and epigenetic differences. Therefore, the thymus 'imprints' distinct gene programs on subsets of innate-like NKT cells that probably impart differences in proliferative capacity, homing, and effector functions.

  16. Altered Cytokine Production By Specific Human Peripheral Blood Cell Subsets Immediately Following Spaceflight

    Science.gov (United States)

    Crucian, Brian E.; Cubbage, Michael L.; Sams, Clarence F.

    1999-01-01

    In this study, we have attempted to combine standard immunological assays with the cellular resolving power of the flow cytometer to positively identify the specific cell types involved in spaceflight-induced immune alterations. We have obtained whole blood samples from 27 astronauts collected at three timepoints (L-10, R+0 and R+3) surrounding four recent space shuttle missions. The duration of these missions ranged from 10 to 18 days. Assays performed included serum/urine cortisol, comprehensive subset phenotyping, assessment of cellular activation markers and intracellular cytokine production following mitogenic stimulation. Absolute levels of peripheral granulocytes were significantly elevated following spaceflight, but the levels of circulating lymphocytes and monocytes were unchanged. Lymphocyte subset analysis demonstrated trends towards a decreased percentage of T cells and an increased percentage of B cells. Nearly all of the astronauts exhibited an increased CD4:CD8 ratio, which was dramatic in some individuals. Assessment of memory (CD45RA+) vs. naive (CD45RO+) CD4+ T cell subsets was more ambiguous, with subjects tending to group more as a flight crew. All subjects from one mission demonstrated an increased CD45RA:CD45RO ratio, while all subjects from another Mission demonstrated a decreased ratio. While no significant trend was seen in the monocyte population as defined by scatter, a decreased percentage of the CD14+ CD16+ monocyte subset was seen following spaceflight in all subjects tested. In general, most of the cellular changes described above which were assessed at R+O and compared to L-10 trended to pre-flight levels by R+3. Although no significant differences were seen in the expression of the cellular activation markers CD69 and CD25 following exposure to microgravity, significant alterations were seen in cytokine production in response to mitogenic activation for specific subsets. T cell (CD3+) production of IL-2 was significantly decreased

  17. Phenotypic, ultra-structural and functional characterization of bovine peripheral blood dendritic cell subsets

    Science.gov (United States)

    Dendritic cells (DC) are multifunctional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets...

  18. Fluorescent activated cell sorting: an effective approach to study dendritic cell subsets in human atherosclerotic plaques.

    Science.gov (United States)

    Van Brussel, Ilse; Ammi, Rachid; Rombouts, Miche; Cools, Nathalie; Vercauteren, Sven R; De Roover, Dominique; Hendriks, Jeroen M H; Lauwers, Patrick; Van Schil, Paul E; Schrijvers, Dorien M

    2015-02-01

    Different immune cell types are present within atherosclerotic plaques. Dendritic cells (DC) are of special interest, since they are considered as the 'center of the immuniverse'. Identifying inflammatory DC subtypes within plaques is important for a better understanding of the lesion pathogenesis and pinpoints their contribution to the atherosclerotic process. We have developed a flow cytometry-based method to characterize and isolate different DC subsets (i.e. CD11b(+), Clec9A(+) and CD16(+) conventional (c)DC and CD123(+) plasmacytoid (p)DC) in human atherosclerotic plaques. We revealed a predominance of pro-inflammatory CD11b(+) DC in advanced human lesions, whereas atheroprotective Clec9A(+) DC were almost absent. CD123(+) pDC and CD16(+) DC were also detectable in plaques. Remarkably, plaques from distinct anatomical locations exhibited different cellular compositions: femoral plaques contained less CD11b(+) and Clec9A(+) DC than carotid plaques. Twice as many monocytes/macrophages were observed compared to DC. Moreover, relative amounts of T cells/B cells/NK cells were 6 times as high as DC numbers. For the first time, fluorescent activated cell sorting analysis of DC subsets in human plaques indicated a predominance of CD11b(+) cDC, in comparison with other DC subsets. Isolation of the different subsets will facilitate detailed functional analysis and may have significant implications for tailoring appropriate therapy.

  19. Sex-specific DoublesexM expression in subsets of Drosophila somatic gonad cells

    Directory of Open Access Journals (Sweden)

    Oliver Brian

    2007-10-01

    Full Text Available Abstract Background In Drosophila melanogaster, a pre-mRNA splicing hierarchy controls sexual identity and ultimately leads to sex-specific Doublesex (DSX transcription factor isoforms. The male-specific DSXM represses genes involved in female development and activates genes involved in male development. Spatial and temporal control of dsx during embryogenesis is not well documented. Results Here we show that DSXM is specifically expressed in subsets of male somatic gonad cells during embryogenesis. Following testis formation, germ cells remain in contact with DSXM-expressing cells, including hub cells and premeiotic somatic cyst cells that surround germ cells during spermatogenesis in larval and adult testes. Conclusion We show that dsx is transcriptionally regulated in addition to being regulated at the pre-mRNA splicing level by the sex determination hierarchy. The dsx locus is spatially controlled by somatic gonad identity. The continuous expression of DSXM in cells contacting the germline suggests an ongoing short-range influence of the somatic sex determination pathway on germ cell development.

  20. Digital image correlation involves an inverse problem: A regularization scheme based on subset size constraint

    Science.gov (United States)

    Zhan, Qin; Yuan, Yuan; Fan, Xiangtao; Huang, Jianyong; Xiong, Chunyang; Yuan, Fan

    2016-06-01

    Digital image correlation (DIC) is essentially implicated in a class of inverse problem. Here, a regularization scheme is developed for the subset-based DIC technique to effectively inhibit potential ill-posedness that likely arises in actual deformation calculations and hence enhance numerical stability, accuracy and precision of correlation measurement. With the aid of a parameterized two-dimensional Butterworth window, a regularized subpixel registration strategy is established, in which the amount of speckle information introduced to correlation calculations may be weighted through equivalent subset size constraint. The optimal regularization parameter associated with each individual sampling point is determined in a self-adaptive way by numerically investigating the curve of 2-norm condition number of coefficient matrix versus the corresponding equivalent subset size, based on which the regularized solution can eventually be obtained. Numerical results deriving from both synthetic speckle images and actual experimental images demonstrate the feasibility and effectiveness of the set of newly-proposed regularized DIC algorithms.

  1. Expression of SLAM (CD150) cell-surface receptors on human B-cell subsets: from pro-B to plasma cells.

    Science.gov (United States)

    De Salort, Jose; Sintes, Jordi; Llinàs, Laia; Matesanz-Isabel, Jessica; Engel, Pablo

    2011-01-30

    The SLAM (CD150) family receptors are leukocyte cell-surface glycoproteins involved in leukocyte activation. These molecules and their adaptor protein SAP contribute to the effective germinal center formation, generation of high-affinity antibody-secreting plasma cells, and memory B cells, thereby facilitating long-term humoral immune response. Multi-color flow cytometric analysis was performed to determine the expression of CD48 (SLAMF2), CD84 (SLAMF5), CD150 (SLAM or SLAMF1), CD229 (Ly9 or SLAMF3), CD244 (2B4 or SLAMF4), CD319 (CRACC, CS1, or SLAMF7), and CD352 (NTB-A or SLAMF6) on human cell lines and B-cell subsets. The following subsets were assessed: pro-B, pre-B, immature-B, and mature-B cells from bone marrow; transitional and B1/B2 subsets from peripheral blood; and naïve, pre-germinal center, germinal center, memory, plasmablasts, and plasma cells from tonsil and spleen. All receptors were expressed on B cells, with the exception of CD244. SLAM family molecules were widely distributed during B-cell development, maturation and terminal differentiation into plasmablasts and plasma cells, but their expression among various B-cell subsets differed significantly. Such heterogeneous expression patterns suggest that SLAM molecules play an essential and non-redundant role in the control of humoral immune responses.

  2. Phenotypic studies of natural killer cell subsets in human transporter associated with antigen processing deficiency.

    Directory of Open Access Journals (Sweden)

    Jacques Zimmer

    Full Text Available Peripheral blood natural killer (NK cells from patients with transporter associated with antigen processing (TAP deficiency are hyporesponsive. The mechanism of this defect is unknown, but the phenotype of TAP-deficient NK cells is almost normal. However, we noticed a high percentage of CD56(bright cells among total NK cells from two patients. We further investigated TAP-deficient NK cells in these patients and compared them to NK cells from two other TAP-deficient patients with no clinical symptoms and to individuals with chronic inflammatory diseases other than TAP deficiency (chronic lung diseases or vasculitis. Peripheral blood mononuclear cells isolated from venous blood were stained with fluorochrome-conjugated antibodies and the phenotype of NK cells was analyzed by flow cytometry. In addition, (51Chromium release assays were performed to assess the cytotoxic activity of NK cells. In the symptomatic patients, CD56(bright NK cells represented 28% and 45%, respectively, of all NK cells (higher than in healthy donors. The patients also displayed a higher percentage of CD56(dimCD16(- NK cells than controls. Interestingly, this unusual NK cell subtype distribution was not found in the two asymptomatic TAP-deficient cases, but was instead present in several of the other patients. Over-expression of the inhibitory receptor CD94/NKG2A by TAP-deficient NK cells was confirmed and extended to the inhibitory receptor ILT2 (CD85j. These inhibitory receptors were not involved in regulating the cytotoxicity of TAP-deficient NK cells. We conclude that expansion of the CD56(bright NK cell subtype in peripheral blood is not a hallmark of TAP deficiency, but can be found in other diseases as well. This might reflect a reaction of the immune system to pathologic conditions. It could be interesting to investigate the relative distribution of NK cell subsets in various respiratory and autoimmune diseases.

  3. Tailored immune responses: novel effector helper T cell subsets in protective immunity.

    Directory of Open Access Journals (Sweden)

    Ervin E Kara

    2014-02-01

    Full Text Available Differentiation of naïve CD4⁺ cells into functionally distinct effector helper T cell subsets, characterised by distinct "cytokine signatures," is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the T(H1/T(H2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.

  4. Tailored immune responses: novel effector helper T cell subsets in protective immunity.

    Science.gov (United States)

    Kara, Ervin E; Comerford, Iain; Fenix, Kevin A; Bastow, Cameron R; Gregor, Carly E; McKenzie, Duncan R; McColl, Shaun R

    2014-02-01

    Differentiation of naïve CD4⁺ cells into functionally distinct effector helper T cell subsets, characterised by distinct "cytokine signatures," is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the T(H)1/T(H)2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.

  5. Chemokine-mediated distribution of dendritic cell subsets in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Meyer Werner

    2010-10-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC represents one of the most immunoresponsive cancers. Antigen-specific vaccination with dendritic cells (DCs in patients with metastatic RCC has been shown to induce cytotoxic T-cell responses associated with objective clinical responses. Thus, clinical trials utilizing DCs for immunotherapy of advanced RCCs appear to be promising; however, detailed analyses concerning the distribution and function of DC subsets in RCCs are lacking. Methods We characterized the distribution of the different immature and mature myeloid DC subsets in RCC tumour tissue and the corresponding normal kidney tissues. In further analyses, the expression of various chemokines and chemokine receptors controlling the migration of DC subsets was investigated. Results The highest numbers of immature CD1a+ DCs were found within RCC tumour tissue. In contrast, the accumulation of mature CD83+/DC-LAMP+ DCs were restricted to the invasive margin of the RCCs. The mature DCs formed clusters with proliferating T-cells. Furthermore, a close association was observed between MIP-3α-producing tumour cells and immature CCR6+ DC recruitment to the tumour bed. Conversely, MIP-3β and SLC expression was only detected at the tumour border, where CCR7-expressing T-cells and mature DCs formed clusters. Conclusion Increased numbers of immature DCs were observed within the tumour tissue of RCCs, whereas mature DCs were found in increased numbers at the tumour margin. Our results strongly implicate that the distribution of DC subsets is controlled by local lymphoid chemokine expression. Thus, increased expression of MIP-3α favours recruitment of immature DCs to the tumour bed, whereas de novo local expression of SLC and MIP-3β induces accumulation of mature DCs at the tumour margin forming clusters with proliferating T-cells reflecting a local anti-tumour immune response.

  6. Lymphoid organ-resident dendritic cells exhibit unique transcriptional fingerprints based on subset and site.

    Directory of Open Access Journals (Sweden)

    Kutlu G Elpek

    Full Text Available Lymphoid organ-resident DC subsets are thought to play unique roles in determining the fate of T cell responses. Recent studies focusing on a single lymphoid organ identified molecular pathways that are differentially operative in each DC subset and led to the assumption that a given DC subset would more or less exhibit the same genomic and functional profiles throughout the body. Whether the local milieu in different anatomical sites can also influence the transcriptome of DC subsets has remained largely unexplored. Here, we interrogated the transcriptional relationships between lymphoid organ-resident DC subsets from spleen, gut- and skin-draining lymph nodes, and thymus of C57BL/6 mice. For this purpose, major resident DC subsets including CD4 and CD8 DCs were sorted at high purity and gene expression profiles were compared using microarray analysis. This investigation revealed that lymphoid organ-resident DC subsets exhibit divergent genomic programs across lymphoid organs. Interestingly, we also found that transcriptional and biochemical properties of a given DC subset can differ between lymphoid organs for lymphoid organ-resident DC subsets, but not plasmacytoid DCs, suggesting that determinants of the tissue milieu program resident DCs for essential site-specific functions.

  7. CD56 marks human dendritic cell subsets with cytotoxic potential

    NARCIS (Netherlands)

    Roothans, D.; Smits, E.; Lion, E.; Tel, J.; Anguille, S.

    2013-01-01

    Human plasmacytoid and myeloid dendritic cells (DCs), when appropriately stimulated, can express the archetypal natural killer (NK)-cell surface marker CD56. In addition to classical DC functions, CD56+ DCs are endowed with an unconventional cytotoxic capacity.

  8. Phenotypic and functional heterogeneity of macrophages and dendritic cell subsets in the healthy and atherosclerosis-prone aorta.

    Directory of Open Access Journals (Sweden)

    Elena V Galkina

    2012-03-01

    Full Text Available Atherosclerosis continues to be the leading cause of cardiovascular disease. Development of atherosclerosis depends on chronic inflammation in the aorta and multiple immune cells are involved in this process. Importantly, resident macrophages and dendritic cells are present within the healthy aorta, but the functions of these cells remain poorly characterized. Local inflammation within the aortic wall promotes the recruitment of monocytes and dendritic cell precursors to the aorta and micro-environmental factors direct the differentiation of these emigrated cells into multiple subsets of macrophages and dendritic cells. Recent data suggest that several populations of macrophages and dendritic cells can co-exist within the aorta. Although the functions of M1, M2, Mox and M4 macrophages are well characterized in vitro, there is a limited set of data on the role of these populations in atherogenesis in vivo. Recent studies on the origin and the potential role of aortic dendritic cells provide novel insights into the biology of aortic dendritic cell subsets and prospective mechanisms of the immune response in atherosclerosis. This review integrates the results of experiments analyzing heterogeneity of dendritic cells and macrophage subsets in healthy and diseased vessels and briefly discusses the known and potential functions of these cells in atherogenesis.

  9. The Vast Universe of T Cell Diversity: Subsets of Memory Cells and Their Differentiation.

    Science.gov (United States)

    Jandus, Camilla; Usatorre, Amaia Martínez; Viganò, Selena; Zhang, Lianjun; Romero, Pedro

    2017-01-01

    The T cell receptor confers specificity for antigen recognition to T cells. By the first encounter with the cognate antigen, reactive T cells initiate a program of expansion and differentiation that will define not only the ultimate quantity of specific cells that will be generated, but more importantly their quality and functional heterogeneity. Recent achievements using mouse model infection systems have helped to shed light into the complex network of factors that dictate and sustain memory T cell differentiation, ranging from antigen load, TCR signal strength, metabolic fitness, transcriptional programs, and proliferative potential. The different models of memory T cell differentiation are discussed in this chapter, and key phenotypic and functional attributes of memory T cell subsets are presented, both for mouse and human cells. Therapeutic manipulation of memory T cell generation is expected to provide novel unique ways to optimize current immunotherapies, both in infection and cancer.

  10. Label-free haemogram using wavelength modulated Raman spectroscopy for identifying immune-cell subset

    Science.gov (United States)

    Ashok, Praveen C.; Praveen, Bavishna B.; Campbell, Elaine C.; Dholakia, Kishan; Powis, Simon J.

    2014-03-01

    Leucocytes in the blood of mammals form a powerful protective system against a wide range of dangerous pathogens. There are several types of immune cells that has specific role in the whole immune system. The number and type of immune cells alter in the disease state and identifying the type of immune cell provides information about a person's state of health. There are several immune cell subsets that are essentially morphologically identical and require external labeling to enable discrimination. Here we demonstrate the feasibility of using Wavelength Modulated Raman Spectroscopy (WMRS) with suitable machine learning algorithms as a label-free method to distinguish between different closely lying immune cell subset. Principal Component Analysis (PCA) was performed on WMRS data from single cells, obtained using confocal Raman microscopy for feature reduction, followed by Support Vector Machine (SVM) for binary discrimination of various cell subset, which yielded an accuracy >85%. The method was successful in discriminating between untouched and unfixed purified populations of CD4+CD3+ and CD8+CD3+ T lymphocyte subsets, and CD56+CD3- natural killer cells with a high degree of specificity. It was also proved sensitive enough to identify unique Raman signatures that allow clear discrimination between dendritic cell subsets, comprising CD303+CD45+ plasmacytoid and CD1c+CD141+ myeloid dendritic cells. The results of this study clearly show that WMRS is highly sensitive and can distinguish between cell types that are morphologically identical.

  11. slan/M-DC8+ cells constitute a distinct subset of dendritic cells in human tonsils.

    Science.gov (United States)

    Micheletti, Alessandra; Finotti, Giulia; Calzetti, Federica; Lonardi, Silvia; Zoratti, Elisa; Bugatti, Mattia; Stefini, Stefania; Vermi, William; Cassatella, Marco A

    2016-01-05

    Human blood dendritic cells (DCs) include three main distinct subsets, namely the CD1c+ and CD141+ myeloid DCs (mDCs) and the CD303+ plasmacytoid DCs (pDCs). More recently, a population of slan/M-DC8+ cells, also known as "slanDCs", has been described in blood and detected even in inflamed secondary lymphoid organs and non-lymphoid tissues. Nevertheless, hallmarks of slan/M-DC8+ cells in tissues are poorly defined. Herein, we report a detailed characterization of the phenotype and function of slan/M-DC8+ cells present in human tonsils. We found that tonsil slan/M-DC8+ cells represent a unique DC cell population, distinct from their circulating counterpart and also from all other tonsil DC and monocyte/macrophage subsets. Phenotypically, slan/M-DC8+ cells in tonsils display a CD11c+HLA-DR+CD14+CD11bdim/negCD16dim/negCX3CR1dim/neg marker repertoire, while functionally they exhibit an efficient antigen presentation capacity and a constitutive secretion of TNFα. Notably, such DC phenotype and functions are substantially reproduced by culturing blood slan/M-DC8+ cells in tonsil-derived conditioned medium (TDCM), further supporting the hypothesis of a full DC-like differentiation program occurring within the tonsil microenvironment. Taken together, our data suggest that blood slan/M-DC8+ cells are immediate precursors of a previously unrecognizedcompetent DC subset in tonsils, and pave the way for further characterization of slan/M-DC8+ cells in other tissues.

  12. Adhesion of subsets of human blood mononuclear cells to porcine endothelial cells

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Cellular immune response is a major barrier to xenotransplantation, and cell adhesion is the first step in intercellular recognition. Flow-cytometric adhesion assay has been used to investigate the differential adhesions of monocyte (Mo), natural killer cell (NK) and T lymphocyte (T) present within human peripheral blood mononuclear cells (PBMC) to porcine aortic endothelial cells (PAEC), and to demonstrate the effect of human interferon-γ(hIFN-γ) or/and tumor necrosis factor-α (hTNF-α) pretreatment of PAEC on their adhesiveness for different PBMC subsets. The preferential sequence for PBMC subset binding to resting PAEC is Mo, NK and T cells, among which T cells show the slightest adherence; hTNF-α can act across the species, and augment Mo, NK and T cell adhesion ratios by 40%, 110% and 3 times, respectively. These results confirm at the cell level that host Mo and NK cells are major participants in the cellular xenograft rejection, thereby, providing a prerequisite for further studying the human Mo/NK-PAEC interactive mechanisms.

  13. Profiling helper T cell subset gene expression in deer mice

    Directory of Open Access Journals (Sweden)

    Hjelle Brian

    2006-08-01

    Full Text Available Abstract Background Deer mice (Peromyscus maniculatus are the most common mammals in North America and are reservoirs for several zoonotic agents, including Sin Nombre virus (SNV, the principal etiologic agent of hantavirus cardiopulmonary syndrome (HCPS in North America. Unlike human HCPS patients, SNV-infected deer mice show no overt pathological symptoms, despite the presence of virus in the lungs. A neutralizing IgG antibody response occurs, but the virus establishes a persistent infection. Limitations of detailed analysis of deer mouse immune responses to SNV are the lack of reagents and methods for evaluating such responses. Results We developed real-time PCR-based detection assays for several immune-related transcription factor and cytokine genes from deer mice that permit the profiling of CD4+ helper T cells, including markers of Th1 cells (T-bet, STAT4, IFNγ, TNF, LT, Th2 cells (GATA-3, STAT6, IL-4, IL-5 and regulatory T cells (Fox-p3, IL-10, TGFβ1. These assays compare the expression of in vitro antigen-stimulated and unstimulated T cells from individual deer mice. Conclusion We developed molecular methods for profiling immune gene expression in deer mice, including a multiplexed real-time PCR assay for assessing expression of several cytokine and transcription factor genes. These assays should be useful for characterizing the immune responses of experimentally- and naturally-infected deer mice.

  14. Hierarchical modeling for rare event detection and cell subset alignment across flow cytometry samples.

    Directory of Open Access Journals (Sweden)

    Andrew Cron

    Full Text Available Flow cytometry is the prototypical assay for multi-parameter single cell analysis, and is essential in vaccine and biomarker research for the enumeration of antigen-specific lymphocytes that are often found in extremely low frequencies (0.1% or less. Standard analysis of flow cytometry data relies on visual identification of cell subsets by experts, a process that is subjective and often difficult to reproduce. An alternative and more objective approach is the use of statistical models to identify cell subsets of interest in an automated fashion. Two specific challenges for automated analysis are to detect extremely low frequency event subsets without biasing the estimate by pre-processing enrichment, and the ability to align cell subsets across multiple data samples for comparative analysis. In this manuscript, we develop hierarchical modeling extensions to the Dirichlet Process Gaussian Mixture Model (DPGMM approach we have previously described for cell subset identification, and show that the hierarchical DPGMM (HDPGMM naturally generates an aligned data model that captures both commonalities and variations across multiple samples. HDPGMM also increases the sensitivity to extremely low frequency events by sharing information across multiple samples analyzed simultaneously. We validate the accuracy and reproducibility of HDPGMM estimates of antigen-specific T cells on clinically relevant reference peripheral blood mononuclear cell (PBMC samples with known frequencies of antigen-specific T cells. These cell samples take advantage of retrovirally TCR-transduced T cells spiked into autologous PBMC samples to give a defined number of antigen-specific T cells detectable by HLA-peptide multimer binding. We provide open source software that can take advantage of both multiple processors and GPU-acceleration to perform the numerically-demanding computations. We show that hierarchical modeling is a useful probabilistic approach that can provide a

  15. Langerhans cells and subsets of lymphocytes in the nasal mucosa

    DEFF Research Database (Denmark)

    Hellquist-Dahl, B; Olsen, K E; Irander, K;

    1991-01-01

    Langerhans cells and different lymphocytes were studied in the nasal mucosa of 39 woodwork teachers and a control group of 14 healthy subjects. Ten of the woodwork teachers were sensitized as determined by skin prick test. A panel of different monoclonal antibodies was applied on the frozen nasal...

  16. An actin-binding protein, CAP, is expressed in a subset of rat taste bud cells.

    Science.gov (United States)

    Ishimaru, Y; Yasuoka, A; Asano-Miyoshi, M; Abe, K; Emori, Y

    2001-02-12

    Single cell cDNA libraries were constructed from taste bud cells of rat circumvallate papillae. Using three steps of screening, including differential hybridization, sequence analyses and in situ hybridization, a clone encoding a rat homolog of yeast adenylyl cyclase-associated protein (CAP) was identified to be highly expressed in a subset of taste bud cells.

  17. Nfil3 is required for the development of all innate lymphoid cell subsets.

    Science.gov (United States)

    Seillet, Cyril; Rankin, Lucille C; Groom, Joanna R; Mielke, Lisa A; Tellier, Julie; Chopin, Michael; Huntington, Nicholas D; Belz, Gabrielle T; Carotta, Sebastian

    2014-08-25

    Innate lymphoid cell (ILC) populations protect against infection and are essential for lymphoid tissue formation and tissue remodeling after damage. Nfil3 is implicated in the function of adaptive immune lineages and NK cell development, but it is not yet known if Nfil3 regulates other innate lymphoid lineages. Here, we identify that Nfil3 is essential for the development of Peyer's patches and ILC2 and ILC3 subsets. Loss of Nfil3 selectively reduced Peyer's patch formation and was accompanied by impaired recruitment and distribution of lymphocytes within the patches. ILC subsets exhibited high Nfil3 expression and genetic deletion of Nfil3 severely compromised the development of all subsets. Subsequently, Nfil3(-/-) mice were highly susceptible to disease when challenged with inflammatory or infectious agents. Thus, we demonstrate that Nfil3 is a key regulator of the development of ILC subsets essential for immune protection in the lung and gut.

  18. Immune Reactions against Gene Gun Vaccines Are Differentially Modulated by Distinct Dendritic Cell Subsets in the Skin.

    Directory of Open Access Journals (Sweden)

    Corinna Stefanie Weber

    Full Text Available The skin accommodates multiple dendritic cell (DC subsets with remarkable functional diversity. Immune reactions are initiated and modulated by the triggering of DC by pathogen-associated or endogenous danger signals. In contrast to these processes, the influence of intrinsic features of protein antigens on the strength and type of immune responses is much less understood. Therefore, we investigated the involvement of distinct DC subsets in immune reactions against two structurally different model antigens, E. coli beta-galactosidase (betaGal and chicken ovalbumin (OVA under otherwise identical conditions. After epicutaneous administration of the respective DNA vaccines with a gene gun, wild type mice induced robust immune responses against both antigens. However, ablation of langerin+ DC almost abolished IgG1 and cytotoxic T lymphocytes against betaGal but enhanced T cell and antibody responses against OVA. We identified epidermal Langerhans cells (LC as the subset responsible for the suppression of anti-OVA reactions and found regulatory T cells critically involved in this process. In contrast, reactions against betaGal were not affected by the selective elimination of LC, indicating that this antigen required a different langerin+ DC subset. The opposing findings obtained with OVA and betaGal vaccines were not due to immune-modulating activities of either the plasmid DNA or the antigen gene products, nor did the differential cellular localization, size or dose of the two proteins account for the opposite effects. Thus, skin-borne protein antigens may be differentially handled by distinct DC subsets, and, in this way, intrinsic features of the antigen can participate in immune modulation.

  19. Studying the Role for CD4+ T Cell Subsets in Human Lupus

    Science.gov (United States)

    2013-07-01

    subsets in human lupus PRINCIPAL INVESTIGATOR: Insoo Kang, M.D. CONTRACTING...SUBTITLE 5a. CONTRACT NUMBER Studying the role for CD4+ T cell subsets in human lupus 5b. GRANT NUMBER W81XWH-10-1-0150 5c. PROGRAM ELEMENT NUMBER...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT We have investigated whether and how autoimmune complex (AIC) in SLE ( lupus ) can

  20. Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy.

    Science.gov (United States)

    Golubovskaya, Vita; Wu, Lijun

    2016-01-01

    This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy--a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4⁺ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh) and CD8⁺ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.); intracellular markers (FOXP3); epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic); and these differences can be modulated to improve CAR-T therapy. In addition, CD4⁺ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

  1. Different Subsets of T Cells, Memory, Effector Functions, and CAR-T Immunotherapy

    Directory of Open Access Journals (Sweden)

    Vita Golubovskaya

    2016-03-01

    Full Text Available This review is focused on different subsets of T cells: CD4 and CD8, memory and effector functions, and their role in CAR-T therapy––a cellular adoptive immunotherapy with T cells expressing chimeric antigen receptor. The CAR-T cells recognize tumor antigens and induce cytotoxic activities against tumor cells. Recently, differences in T cell functions and the role of memory and effector T cells were shown to be important in CAR-T cell immunotherapy. The CD4+ subsets (Th1, Th2, Th9, Th17, Th22, Treg, and Tfh and CD8+ memory and effector subsets differ in extra-cellular (CD25, CD45RO, CD45RA, CCR-7, L-Selectin [CD62L], etc.; intracellular markers (FOXP3; epigenetic and genetic programs; and metabolic pathways (catabolic or anabolic; and these differences can be modulated to improve CAR-T therapy. In addition, CD4+ Treg cells suppress the efficacy of CAR-T cell therapy, and different approaches to overcome this suppression are discussed in this review. Thus, next-generation CAR-T immunotherapy can be improved, based on our knowledge of T cell subsets functions, differentiation, proliferation, and signaling pathways to generate more active CAR-T cells against tumors.

  2. A method for high purity sorting of rare cell subsets applied to TDC

    OpenAIRE

    2013-01-01

    TDC are a recently described subset of polyclonal αβ T-cells with dendritic cell properties. Because of their low number in peripheral immune compartments, isolation and characterization of TDC with existing purification methods is technically challenging. Here we describe a customized gating strategy and a flow cytometry-based cell sorting protocol for isolation of TDC. The protocol was developed because, despite very conservative gating for dead-cell and doublet exclusion, cells obtained wi...

  3. Human NK Cell Subsets in Pregnancy and Disease: Toward a New Biological Complexity

    Science.gov (United States)

    Cristiani, Costanza Maria; Palella, Eleonora; Sottile, Rosa; Tallerico, Rossana; Garofalo, Cinzia; Carbone, Ennio

    2016-01-01

    In humans, NK cells are mainly identified by the surface expression levels of CD56 and CD16, which differentiate between five functionally different NK cell subsets. However, nowadays NK cells are considered as a more heterogeneous population formed by various subsets differing in function, surface phenotype, and anatomic localization. In human CMV- and hantaviruses-infected subjects, an increased frequency of a NKG2A−CD57+NKG2C+ NK cell subset has been observed, while the phenotype of the NK cell subpopulation associated with cancer may vary according to the specific kind of tumor and its anatomical location. The healthy human lymph nodes contain mainly the CD56bright NK cell subset while in melanoma metastatic lymph nodes the CD56dimCD57+KIR+CCR7+ NK cell subpopulation prevails. The five NK cell subpopulations are found in breast cancer patients, where they differ for expression pattern of chemokine receptors, maturation stage, functional capabilities. In pregnancy, uterine NK cells show a prevalence of the CD56brightCD16− NK cell compartment, whose activity is influenced by KIRs repertoire. This NK cell subset’s super specialization could be explained by (i) the expansion of single mature CD56dim clones, (ii) the recruitment and maturation of CD56bright NK cells through specific stimuli, and (iii) the in situ development of tumor-resident NK cells from tissue-resident CD56bright NK cells independently of the circulating NK cell compartment. This new and unexpected biological feature of the NK cell compartment could be an important source of new biomarkers to improve patients’ diagnosis. PMID:28082990

  4. Phenotypic and functional heterogeneity of macrophages and dendritic cell subsets in the healthy and atherosclerosis-prone aorta.

    Science.gov (United States)

    Butcher, Matthew J; Galkina, Elena V

    2012-01-01

    Atherosclerosis continues to be the leading cause of cardiovascular disease. Development of atherosclerosis depends on chronic inflammation in the aorta and multiple immune cells are involved in this process. Importantly, resident macrophages and dendritic cells (DCs) are present within the healthy aorta, but the functions of these cells remain poorly characterized. Local inflammation within the aortic wall promotes the recruitment of monocytes and DC precursors to the aorta and micro-environmental factors direct the differentiation of these emigrated cells into multiple subsets of macrophages and DCs. Recent data suggest that several populations of macrophages and DCs can co-exist within the aorta. Although the functions of M1, M2, Mox, and M4 macrophages are well characterized in vitro, there is a limited set of data on the role of these populations in atherogenesis in vivo. Recent studies on the origin and the potential role of aortic DCs provide novel insights into the biology of aortic DC subsets and prospective mechanisms of the immune response in atherosclerosis. This review integrates the results of experiments analyzing heterogeneity of DCs and macrophage subsets in healthy and diseased vessels and briefly discusses the known and potential functions of these cells in atherogenesis.

  5. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity

    OpenAIRE

    D’Angelo, Rosemarie C.; Ouzounova, Maria; Davis, April; Choi, Daejin; Tchuenkam, Stevie M.; Kim, Gwangil; Luther, Tahra; Quraishi, Ahmed A.; Senbabaoglu, Yasin; Conley, Sarah J; Shawn G Clouthier; Hassan, Khaled A.; Wicha, Max S; Korkaya, Hasan

    2015-01-01

    Developmental pathways such as Notch play a pivotal role in tissue specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch+) or reduced activity (Notch-) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays we investigated the role of Notch ...

  6. A method for high purity sorting of rare cell subsets applied to TDC.

    Science.gov (United States)

    Kuka, Mirela; Ashwell, Jonathan D

    2013-12-31

    T(DC) are a recently described subset of polyclonal αβ T-cells with dendritic cell properties. Because of their low number in peripheral immune compartments, isolation and characterization of T(DC) with existing purification methods are technically challenging. Here we describe a customized gating strategy and a flow cytometry-based cell sorting protocol for isolation of T(DC). The protocol was developed because, despite very conservative gating for dead-cell and doublet exclusion, cells obtained with normal sorting procedures were enriched for T(DC) but not pure. Re-sorting the output of the first round of sorting results in highly pure T(DC). Cells obtained with this method are viable and can be used for in vitro characterization. Moreover, this double-round sorting strategy can be universally applied to the isolation of other rare cell subsets.

  7. Liver grafts contain a unique subset of natural killer cells that are transferred into the recipient after liver transplantation.

    Science.gov (United States)

    Moroso, Viviana; Metselaar, Herold J; Mancham, Shanta; Tilanus, Hugo W; Eissens, Diana; van der Meer, Arnold; van der Laan, Luc J W; Kuipers, Ernst J; Joosten, Irma; Kwekkeboom, Jaap

    2010-07-01

    In contrast to other solid organ transplantations, liver grafts have tolerogenic properties. Animal models indicate that donor leukocytes transferred into the recipient after liver transplantation (LTX) play a relevant role in this tolerogenic phenomenon. However, the specific donor cell types involved in modulation of the recipient alloresponse are not yet defined. We hypothesized that this unique property of liver grafts may be related to their high content of organ-specific natural killer (NK) and CD56(+) T cells. Here, we show that a high proportion of hepatic NK cells that detach from human liver grafts during pretransplant perfusion belong to the CD56bright subset, and are in an activated state (CD69(+)). Liver NK cells contained perforin and granzymes, exerted stronger cytotoxicity against K562 target cells when compared with blood NK cells, and secreted interferon-gamma, but no interleukin-10 or T helper 2 cytokines, upon stimulation with monokines. Interestingly, whereas the CD56bright subset is classically considered as noncytolytic, liver CD56bright NK cells showed a high content of cytolytic molecules and degranulated in response to K562 cells. After LTX, but not after renal transplantation, significant numbers of donor CD56dim NK and CD56(+) T cells were detected in the recipient circulation for approximately 2 weeks. In conclusion, during clinical LTX, activated and highly cytotoxic NK cells of donor origin are transferred into the recipient, and a subset of them mixes with the recirculating recipient NK cell pool. The unique properties of the transferred hepatic NK cells may enable them to play a role in regulating the immunological response of the recipient against the graft and therefore contribute to liver tolerogenicity.

  8. T cell subsets in human airways prior to and following endobronchial administration of endotoxin

    DEFF Research Database (Denmark)

    Ronit, Andreas; Plovsing, Ronni R; Gaardbo, Julie C

    2015-01-01

    BACKGROUND AND OBJECTIVES: Bronchial instillation of lipopolysaccharide (LPS) provides a reversible model of lung inflammation that may resemble early stages of acute respiratory distress syndrome (ARDS). We investigated the distributions of T-cell subsets in the human airways and sought to deter...

  9. Phenotypic, ultra-structural, and functional characterization of bovine peripheral blood dendritic cell subsets.

    Directory of Open Access Journals (Sweden)

    Janet J Sei

    Full Text Available Dendritic cells (DC are multi-functional cells that bridge the gap between innate and adaptive immune systems. In bovine, significant information is lacking on the precise identity and role of peripheral blood DC subsets. In this study, we identify and characterize bovine peripheral blood DC subsets directly ex vivo, without further in vitro manipulation. Multi-color flow cytometric analysis revealed that three DC subsets could be identified. Bovine plasmacytoid DC were phenotypically identified by a unique pattern of cell surface protein expression including CD4, exhibited an extensive endoplasmic reticulum and Golgi apparatus, efficiently internalized and degraded exogenous antigen, and were the only peripheral blood cells specialized in the production of type I IFN following activation with Toll-like receptor (TLR agonists. Conventional DC were identified by expression of a different pattern of cell surface proteins including CD11c, MHC class II, and CD80, among others, the display of extensive dendritic protrusions on their plasma membrane, expression of very high levels of MHC class II and co-stimulatory molecules, efficient internalization and degradation of exogenous antigen, and ready production of detectable levels of TNF-alpha in response to TLR activation. Our investigations also revealed a third novel DC subset that may be a precursor of conventional DC that were MHC class II+ and CD11c-. These cells exhibited a smooth plasma membrane with a rounded nucleus, produced TNF-alpha in response to TLR-activation (albeit lower than CD11c+ DC, and were the least efficient in internalization/degradation of exogenous antigen. These studies define three bovine blood DC subsets with distinct phenotypic and functional characteristics which can be analyzed during immune responses to pathogens and vaccinations of cattle.

  10. Three distinct subsets of thymic epithelial cells in rats and mice defined by novel antibodies.

    Directory of Open Access Journals (Sweden)

    Yasushi Sawanobori

    Full Text Available AIM: Thymic epithelial cells (TECs are thought to play an essential role in T cell development and have been detected mainly in mice using lectin binding and antibodies to keratins. Our aim in the present study was to create a precise map of rat TECs using antibodies to putative markers and novel monoclonal antibodies (i.e., ED 18/19/21 and anti-CD205 antibodies and compare it with a map from mouse counterparts and that of rat thymic dendritic cells. RESULTS: Rat TECs were subdivided on the basis of phenotype into three subsets; ED18+ED19+/-keratin 5 (K5+K8+CD205+ class II MHC (MHCII+ cortical TECs (cTECs, ED18+ED21-K5-K8+Ulex europaeus lectin 1 (UEA-1+CD205- medullary TECs (mTEC1s, and ED18+ED21+K5+K8dullUEA-1-CD205- medullary TECs (mTEC2s. Thymic nurse cells were defined in cytosmears as an ED18+ED19+/-K5+K8+ subset of cTECs. mTEC1s preferentially expressed MHCII, claudin-3, claudin-4, and autoimmune regulator (AIRE. Use of ED18 and ED21 antibodies revealed three subsets of TECs in mice as well. We also detected two distinct TEC-free areas in the subcapsular cortex and in the medulla. Rat dendritic cells in the cortex were MHCII+CD103+ but negative for TEC markers, including CD205. Those in the medulla were MHCII+CD103+ and CD205+ cells were found only in the TEC-free area. CONCLUSION: Both rats and mice have three TEC subsets with similar phenotypes that can be identified using known markers and new monoclonal antibodies. These findings will facilitate further analysis of TEC subsets and DCs and help to define their roles in thymic selection and in pathological states such as autoimmune disorders.

  11. Interleukin-6 autoantibodies are involved in the pathogenesis of a subset of type 2 diabetes

    DEFF Research Database (Denmark)

    Fosgerau, K; Galle, P; Hansen, Torben

    2010-01-01

    Interleukin-6 (IL6) is critically involved in inflammation and metabolism. About 1% of people produce IL6 autoantibodies (aAb-IL6) that impair IL6 signaling in vivo. We tested the hypothesis that the prevalence of such aAb-IL6 is increased in type 2 diabetic patients and that aAb-IL6 plays a direct...... role in causing hyperglycemia. In humans, the prevalence of circulating high-affinity neutralizing aAb-IL6 was 2.5% in the type 2 diabetic patients and 1% in the controls (odds ratio 2.5, 95% confidence interval 1.2-4.9, P=0.01). To test for the role of aAb-IL6 in causing hyperglycemia, such aAb-IL6...... were induced in mice by a validated vaccination procedure. Mice with plasma levels of aAb-IL6 similar to the 2.5% type 2 diabetic patients developed obesity and impaired glucose tolerance (area under the curve (AUC) glucose, 2056+/-62 vs 1793+/-62, P=0.05) as compared with sham-vaccinated mice, when...

  12. Memory T cell subsets in tuberculosis: what should we be targeting?

    Science.gov (United States)

    Henao-Tamayo, Marcela; Ordway, Diane J; Orme, Ian M

    2014-09-01

    The purpose of vaccination is to establish a stable population of long lived memory T cells. In the context of tuberculosis, the BCG vaccine has been widely used for well over 60 years, but during that time its weaknesses, particularly its ineffectiveness in adults, has been increasingly recognized. In this commentary we review what is known about memory T cells, both in general and in the context of their role in expressing specific acquired resistance to tuberculosis. Current knowledge indicates that both effector memory and central memory can be generated, depending on the experimental conditions, but both in animal models and in clinical studies it is clear that effector memory T cells are the predominant subset. These issues are of importance, given the concerted effort to make new TB vaccines, not all of which may work in precisely the same manner. At the present time whether a TB vaccine would work better if it targeted one specific T cell subset rather than another is as yet completely unknown, and this is now further complicated by new evidence that suggests other subsets such as IL-17 secreting CD4 T cells and cells with stem cell-like qualities may also play important roles.

  13. Mathematical analysis of mis-estimation of cell subsets in flow cytometry: viability staining revisited.

    Science.gov (United States)

    Petrunkina, A M; Harrison, R A P

    2011-05-31

    Many research projects in cell biology now use flow cytometry for analysis or for isolation of specific cell types. In such studies, cell viability is obviously a crucial issue. However, many studies appear to rely upon light-scattering characteristics to identify and gate out non-viable cells, despite the fact that reliable identification of such cells can only be achieved through staining with impermeable fluorescent nuclear dyes such as propidium iodide or 7-amino actinomycin. In this paper we apply mathematical analysis to the theoretical problem of quantifying cell sub-populations labeled with two or more fluorescent markers, comparing situations in which dead cells have been identified with those in which cell viability has not been assessed. We demonstrate that in all cases in which dead cells are present within the population, percentages of live sub-populations in different subsets are mis-estimated. In cases where the pattern of marker expression differs greatly between live and dead cells, or where the proportion of dead cells is high, this mis-estimation will be aggravated; the subsets pattern will therefore be biased in a population selected only on the basis of light-scatter behavior. The importance of accurately detecting and gating out dead cells is illustrated by an experimental example accompanying the mathematical analysis. To conclude, identification of dead cells by means of viability stains should be an absolute routine in practical flow cytometry, so as to avoid mis-estimation in sorting or analysis.

  14. EFFECT OF PARTURITION ON WHITE BLOOD CELLS COUNT (WBC AND T CELLS SUBSETS IN SELENIUM SUPPLEMENTED NEWBORN LAMBS

    Directory of Open Access Journals (Sweden)

    L. PISEK

    2013-12-01

    Full Text Available The aim of the work was assessed the influence of parturition at the dynamics of leukocytes and T cells subsets in a selenium supplemented newborn lambs. The experiment was conducted on nineteen sucking newborn lambs of the Sumava sheep breed. After parturition blood samples were taken from lambs on day 10, 30 and 60. The WBC in blood smear was detected by microscopically analysis (norm no. 84 3206, and the CD4+ and CD8+ T cells subsets in blood were detected by flow cytometery. The WBC was in physiological norm. The highest WBC was founded on 30th day of the experiment. In the dynamics of the CD4+ a CD8+ T cells subsets were founded statistically significant differences: In the CD4+ subset between 10th and 30th day of the experiment (P < 0.001 and between 30th and 60th day of the experiment (P < 0.01, and in the CD8+ subset between 10th and 30th day of the experiment (P < 0.001. Excepted in 30th day of the experiment were counts of the CD4+ and CD8+ T cells subsets inside the physiological norm.

  15. A systems biology approach to the analysis of subset-specific responses to lipopolysaccharide in dendritic cells.

    Directory of Open Access Journals (Sweden)

    David G Hancock

    Full Text Available Dendritic cells (DCs are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 commitment, generating inducible Tregs, and mediating tolerance. It is believed that distinct DC subsets have evolved to control these different immune outcomes. However, how DC subsets mount different responses to inflammatory and/or tolerogenic signals in order to accomplish their divergent functions remains unclear. Lipopolysaccharide (LPS provides an excellent model for investigating responses in closely related splenic DC subsets, as all subsets express the LPS receptor TLR4 and respond to LPS in vitro. However, previous studies of the LPS-induced DC transcriptome have been performed only on mixed DC populations. Moreover, comparisons of the in vivo response of two closely related DC subsets to LPS stimulation have not been reported in the literature to date. We compared the transcriptomes of murine splenic CD8 and CD11b DC subsets after in vivo LPS stimulation, using RNA-Seq and systems biology approaches. We identified subset-specific gene signatures, which included multiple functional immune mediators unique to each subset. To explain the observed subset-specific differences, we used a network analysis approach. While both DC subsets used a conserved set of transcription factors and major signalling pathways, the subsets showed differential regulation of sets of genes that 'fine-tune' the network Hubs expressed in common. We propose a model in which signalling through common pathway components is 'fine-tuned' by transcriptional control of subset-specific modulators, thus allowing for distinct functional outcomes in closely related DC subsets. We extend this analysis to comparable datasets from the literature and confirm that our model can account for cell subset-specific responses to LPS stimulation in multiple subpopulations in mouse and man.

  16. Vitamin D modulates different IL-17-secreting T cell subsets in multiple sclerosis patients.

    Science.gov (United States)

    da Costa, Denise S M Medrado; Hygino, Joana; Ferreira, Thais B; Kasahara, Taissa M; Barros, Priscila O; Monteiro, Clarice; Oliveira, Aleida; Tavares, Felipe; Vasconcelos, Claudia Cristina; Alvarenga, Regina; Bento, Cleonice A M

    2016-10-15

    Vitamin D deficiency is an environmental risk factor for MS, a Th17 cell-mediated autoimmune disease that results in demyelination in the CNS. Therefore, we aimed to evaluate the ability of in vitro 1,25(OH)2D in modulating different Th17 cell subsets in MS patients in remission phase. In the present study, the production of Th17-related cytokines (IL-1β, IL-6, IL-17, IL-22), as well as GM-CSF, was significantly higher in cell cultures from MS patients than in healthy subjects (HS). The 1,25(OH)2D reduced all pro-inflammatory cytokines essayed, mainly those released from HS cell cultures. The proportion of both IL-17(+)IFN-γ(+) (CD4(+) and CD8(+)) T cells and IL-17(+)IFN-γ(-)CD8(+) T cells was positively related with neurological disorders, determined by EDSS score. The addition of 1,25(OH)2D reduced not only these pathogenic T cell subsets but elevated the percentage of IL-10-secreting conventional (FoxP3(+)CD25(+)CD127(-)CD4(+)) and non-conventional (IL-17(+)) regulatory-like T cells. Taken together, the results indicate that the active form of vitamin D should benefit MS patients by attenuating the percentage of pathogenic T cells. This effect could be direct and/or indirect, by enhancing classical and non-classical regulatory T cells.

  17. Changes in Circulating B Cell Subsets Associated with Aging and Acute SIV Infection in Rhesus Macaques

    Science.gov (United States)

    Gonzalez, Denise F.; Kieu, Hung T.; Castillo, Luis D.; Messaoudi, Ilhem; Shen, Xiaoying; Tomaras, Georgia D.; Shacklett, Barbara L.; Barry, Peter A.; Sparger, Ellen E.

    2017-01-01

    Aging and certain viral infections can negatively impact humoral responses in humans. To further develop the nonhuman primate (NHP) model for investigating B cell dynamics in human aging and infectious disease, a flow cytometric panel was developed to characterize circulating rhesus B cell subsets. Significant differences between human and macaque B cells included the proportions of cells within IgD+ and switched memory populations and a prominent CD21-CD27+ unswitched memory population detected only in macaques. We then utilized the expanded panel to analyze B cell alterations associated with aging and acute simian immunodeficiency virus (SIV) infection in the NHP model. In the aging study, distinct patterns of B cell subset frequencies were observed for macaques aged one to five years compared to those between ages 5 and 30 years. In the SIV infection study, B cell frequencies and absolute number were dramatically reduced following acute infection, but recovered within four weeks of infection. Thereafter, the frequencies of activated memory B cells progressively increased; these were significantly correlated with the magnitude of SIV-specific IgG responses, and coincided with impaired maturation of anti-SIV antibody avidity, as previously reported for HIV-1 infection. These observations further validate the NHP model for investigation of mechanisms responsible for B cells alterations associated with immunosenescence and infectious disease. PMID:28095513

  18. The network of cytokines, receptors and transcription factors governing the development of dendritic cell subsets

    OpenAIRE

    Sathe, Priyanka; Wu, Li

    2011-01-01

    The pathways leading to the development of different dendritic cell (DC) subsets have long been unclear. In recent years, a number of precursors on the route to DC development, both under steady state and inflammatory conditions, have been described, and the nature of these pathways is becoming clearer. In addition, the development of various knockout mouse models and an in vitro system modelling DC development have revealed the role of numerous cytokines and transcription factors that influe...

  19. PD1-Expressing T Cell Subsets Modify the Rejection Risk in Renal Transplant Patients

    Science.gov (United States)

    Pike, Rebecca; Thomas, Niclas; Workman, Sarita; Ambrose, Lyn; Guzman, David; Sivakumaran, Shivajanani; Johnson, Margaret; Thorburn, Douglas; Harber, Mark; Chain, Benny; Stauss, Hans J.

    2016-01-01

    We tested whether multi-parameter immune phenotyping before or after renal ­transplantation can predict the risk of rejection episodes. Blood samples collected before and weekly for 3 months after transplantation were analyzed by multi-parameter flow cytometry to define 52 T cell and 13 innate lymphocyte subsets in each sample, producing more than 11,000 data points that defined the immune status of the 28 patients included in this study. Principle component analysis suggested that the patients with histologically confirmed rejection episodes segregated from those without rejection. Protein death 1 (PD-1)-expressing subpopulations of regulatory and conventional T cells had the greatest influence on the principal component segregation. We constructed a statistical tool to predict rejection using a support vector machine algorithm. The algorithm correctly identified 7 out of 9 patients with rejection, and 14 out of 17 patients without rejection. The immune profile before transplantation was most accurate in determining the risk of rejection, while changes of immune parameters after transplantation were less accurate in discriminating rejection from non-rejection. The data indicate that pretransplant immune subset analysis has the potential to identify patients at risk of developing rejection episodes, and suggests that the proportion of PD1-expressing T cell subsets may be a key indicator of rejection risk. PMID:27148254

  20. The Role of T cell Subsets and Cytokines Involved in the Pathogenesis of Recurrent Vulvovaginal Candidiasis%T细胞亚群及相关细胞因子在复发性外阴阴道念珠菌病发病中的作用

    Institute of Scientific and Technical Information of China (English)

    李俊艳; 占志萍; 孔祥君; 李维云; 聂振华

    2011-01-01

    目的 探讨T细胞亚群及局部分泌物中相关的细胞因子在复发性外阴阴道念珠菌病发病机制中的作用.方法 采用碱性磷酸酶-抗碱性磷酸酶(APAAP)桥联酶法技术,对28例外阴阴道念珠菌病(VVC)、35例复发性外阴阴道念珠菌病(RVVC)和31例健康对照者外周血进行T淋巴细胞亚群CD4+,CD8+细胞检测,EUSA法检测以上各组女性阴道分泌物中IL-12,IL-4和IFN-γ的表达水平.结果 RVVC组CD4+T淋巴细胞低于VVC组和对照组(P均0.05),但均高于对照组(P均0.05).结论 复发性外阴阴道念珠菌病患者可能存在一定的免疫缺陷,Th1型和Th2型细胞因子的表达异常可能与外阴阴道念珠菌病的发病以及复发有关.%Objective To study the role of T cell subsets and cytokine involved in the vaginal secretions of vulvovaginal candidiasis patients in the pathogenesis of recurrent vulvovaginal candidiasis. Methods Alkaline phosphatase-anti-alkaline phosphatas (APAAP) was used to detect CD4 + and CD8 +T lymphocytes of 28 cases vulvovaginal candidiasis(VVS) ,35 cases recurrent vulvovaginal candidiasis (RVVC) patients and 31 cases health control. The expression level of IL-4,IL-12,IFN-γ in the vaginal secretions from vulvovaginal candidiasis patients were detected by ELISA and compared with that from normal controls. Results CD4 + T ymphocytes in recurrent groups were lower than that of original and normal control groups, and CD8 + T lymphocytes were higher than that of original and normal control groups. The level of IL-12 in original groups was the hightest in the three groups,while no significant difference in IFN-γ between recurrent and original groups was found , and yet higher than that in normal control groups. There was no significant difference in IL-4 in these three groups. Conclusions Certain immune deficiencies were found in the patients of recurrent vulvovaginal candidiasis. The abnormal expression of Th1 type and Th2 type cytokines may be associated

  1. Extra-thymically induced T regulatory cell subsets: the optimal target for antigen-specific immunotherapy

    Science.gov (United States)

    Verhagen, Johan; Wegner, Anja; Wraith, David C

    2015-01-01

    Antigen-specific immunotherapy aims to selectively restore tolerance to innocuous antigens in cases of autoimmune or allergic disease, without the need for general immune suppression. Although the principle of antigen-specific immunotherapy was discovered more than a century ago, its clinical application to date is limited, particularly in the control of autoimmunity. This has resulted mainly from a lack of in-depth understanding of the underlying mechanism. More recently, the differentiation of extra-thymically induced T regulatory (Treg) cell subsets has been shown to be instrumental in peripheral tolerance induction. Two main types of inducible Treg cells, interleukin-10-secreting or Foxp3+, have now been described, each with distinct characteristics and methods of therapeutic induction. It is crucial, therefore, to identify the suitability of either subset in the control of specific immune disorders. This review explores their natural function, the known mechanisms of therapeutic differentiation of either subset as well as their in vivo functionality and discusses new developments that may aid their use in antigen-specific immunotherapy, with a focus on autoimmune disease. PMID:25716063

  2. PIM kinases as potential therapeutic targets in a subset of peripheral T cell lymphoma cases.

    Directory of Open Access Journals (Sweden)

    Esperanza Martín-Sánchez

    Full Text Available Currently, there is no efficient therapy for patients with peripheral T cell lymphoma (PTCL. The Proviral Integration site of Moloney murine leukemia virus (PIM kinases are important mediators of cell survival. We aimed to determine the therapeutic value of PIM kinases because they are overexpressed in PTCL patients, T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically (using small interfering and short hairpin RNAs and pharmacologically (mainly with the pan-PIM inhibitor (PIMi ETP-39010 in a panel of 8 PTCL cell lines. Effects on cell viability, apoptosis, cell cycle, key proteins and gene expression were evaluated. Individual inhibition of each of the PIM genes did not affect PTCL cell survival, partially because of a compensatory mechanism among the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in part through the induction of DNA damage. Therefore, pan-PIMi synergized with Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral T cell viability without affecting normal T cells ex vivo. Since anaplastic large cell lymphoma (ALK+ ALCL cell lines were the most sensitive to the pan-PIMi, we tested the simultaneous inhibition of ALK and PIM kinases and found a strong synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase inhibition could be of therapeutic value in a subset of PTCL, especially when combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL.

  3. A Study on Peripheral T Cell Subsets in Patients with Thyroid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Soo [Pusan National University College of Medicine, Pusan (Korea, Republic of)

    1991-03-15

    To elucidate alteration of peripheral T cell subsets in thyroid tumors, the author enumerated T cell subsets in peripheral blood by indirect immunofluorescent method, using monoclonal antibodies (CD3, CD4 and CD8) in 17 cases of thyroid cancer, 12 cases of thyroid adenoma, and 16 cases of adult healthy subjects as controls. Diagnoses were confirmed histopathologically in thyroid cancer and adenoma, and were established on the basis of commonly accepted clinical and biochemical criteria in Hashimoto's thyroiditis. The blood was drawn from veins of (he patients and control subjects in Pusan National University Hospital during the period of January to October 1990. The results obtained were summarized as follow: 1) The percentage of CD3+ cells was significantly decreased in thyroid cancer as compared with healthy subjects. 2) The percentage of CD4+ cells was not different among thyroid cancer, thyroid adenoma, hashimoto's thyroiditis and control subjects each other. 3) The percentage of CD8+ cells was significantly decreased in thyroid cancer as compared with adult healthy subjects, and tended to be decreased as compared with thyroid adenoma and Hashimoto's thyroiditis. 4) The CD/CDH ratio was significantly increased in thyroid cancer as compared with control subjects, and tended to be increased as compared with thyroid adenoma and Hashimoto's thyroiditis. On the basis of (the results, it can be suggested that the immunodysfunction may be due to decreased suppressor/cytotoxic T cells in thyroid cancer.

  4. The Role of Different Subsets of Regulatory T Cells in Immunopathogenesis of Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Maryam Gol-Ara

    2012-01-01

    Full Text Available Rheumatoid arthritis (RA is a common autoimmune disease and a systemic inflammatory disease which is characterized by chronic joint inflammation and variable degrees of bone and cartilage erosion and hyperplasia of synovial tissues. Considering the role of autoreactive T cells (particularly Th1 and Th17 cells in pathophysiology of RA, it might be assumed that the regulatory T cells (Tregs will be able to control the initiation and progression of disease. The frequency, function, and properties of various subsets of Tregs including natural Tregs (nTregs, IL-10-producing type 1 Tregs (Tr1 cells, TGF-β-producing Th3 cells, CD8+ Tregs, and NKT regulatory cells have been investigated in various studies associated with RA and collagen-induced arthritis (CIA as experimental model of this disease. In this paper, we intend to submit the comprehensive information about the immunobiology of various subsets of Tregs and their roles and function in immunopathophysiology of RA and its animal model, CIA.

  5. Histone demethylase Jmjd3 is required for the development of subsets of retinal bipolar cells.

    Science.gov (United States)

    Iida, Atsumi; Iwagawa, Toshiro; Kuribayashi, Hiroshi; Satoh, Shinya; Mochizuki, Yujin; Baba, Yukihiro; Nakauchi, Hiromitsu; Furukawa, Takahisa; Koseki, Haruhiko; Murakami, Akira; Watanabe, Sumiko

    2014-03-11

    Di- and trimethylation of lysine 27 on histone H3 (H3K27me2/3) is an important gene repression mechanism. H3K27me2/3-specific demethylase, Jmjd3, was expressed in the inner nuclear layer during late retinal development. In contrast, H3K27 methyltransferase, Ezh2, was highly expressed in the embryonic retina but its expression decreased rapidly after birth. Jmjd3 loss of function in the developing retina resulted in failed differentiation of PKC-positive bipolar cell subsets (rod-ON-BP) and reduced transcription factor Bhlhb4 expression, which is critical for the differentiation of rod-ON-BP cells. Overexpression of Bhlhb4, but not of other BP cell-related genes, such as transcription factors Neurod and Chx10, in Jmjd3-knockdown retina rescued loss of PKC-positive BP cells. Populations of other retinal cell subsets were not significantly affected. In addition, proliferation activity and apoptotic cell number during retinal development were not affected by the loss of Jmjd3. Levels of histone H3 trimethyl Lys27 (H3K27me3) in the Bhlhb4 locus were lower in Islet-1-positive BP cells and amacrine cells than in the Islet-1-negative cell fraction. The Islet-1-negative cell fraction consisted mainly of photoreceptors, suggestive of lineage-specific demethylation of H3K27me3 in the Bhlhb4 locus. We propose that lineage-specific H3K27me3 demethylation of critical gene loci by spatiotemporal-specific Jmjd3 expression is required for appropriate maturation of retinal cells.

  6. IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation.

    Science.gov (United States)

    Lindenberg, Jelle J; Oosterhoff, Dinja; Sombroek, Claudia C; Lougheed, Sinéad M; Hooijberg, Erik; Stam, Anita G M; Santegoets, Saskia J A M; Tijssen, Henk J; Buter, Jan; Pinedo, Herbert M; van den Eertwegh, Alfons J M; Scheper, Rik J; Koenen, Hans J P M; van de Ven, Rieneke; de Gruijl, Tanja D

    2013-01-01

    In cancer patients pervasive systemic suppression of Dendritic Cell (DC) differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC) and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14(+)CD141(+)DC-SIGN(+) DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a(+) subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8(+) T cells, migration of immature CD14(+) DDC was accompanied by increased release of IL-10, poor expansion of CD4(+) and CD8(+) T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.

  7. IL-10 conditioning of human skin affects the distribution of migratory dendritic cell subsets and functional T cell differentiation.

    Directory of Open Access Journals (Sweden)

    Jelle J Lindenberg

    Full Text Available In cancer patients pervasive systemic suppression of Dendritic Cell (DC differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14(+CD141(+DC-SIGN(+ DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a(+ subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8(+ T cells, migration of immature CD14(+ DDC was accompanied by increased release of IL-10, poor expansion of CD4(+ and CD8(+ T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.

  8. Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4.

    NARCIS (Netherlands)

    Joosten, S.A.; Meijgaarden, K.E. van; Savage, N.D.; Boer, T. de; Triebel, F.; Wal, A. van der; Heer, E. de; Klein, M.R.; Geluk, A.; Ottenhoff, T.H.M.

    2007-01-01

    Regulatory T cells (Treg) comprise multiple subsets and are important in controlling immunity and inflammation. However, the induction and mode of action of the various distinct Treg subsets remain ill defined, particularly in humans. Here, we describe a human CD8+ lymphocyte activation gene-3 (LAG-

  9. Effect of T cell subset and inflammatory cytokine levels on prognosis in patients with pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)

    Cheng-Zhou Wu; Yan-Qiao Wu

    2016-01-01

    Objective:To explore the effect of T cell subset and inflammatory cytokine levels on the prognosis in patients with pulmonary tuberculosis.Methods:A total of 72 patients confirmed with pulmonary tuberculosis who were admitted in our hospital from February, 2013 to February, 2015 were included in the study and served as the experiment group, among which 58 cases had active tuberculosis, and 14 cases had static tuberculosis; while 50 healthy individuals who came for physical examinations were served as the control group. The sputum bacteria before treatment and 6 months after treatment in the two groups were detected. The sputum negative conversion rate was recorded. The absorption of pulmonary lesions and the closure of tuberculosis cavity were examined. The immune cell function of T cell subset was detected again.Results: The peripheral blood CD3, CD4, CD8, and CD4/CD8 levels in the experiment group were significantly lower than those in the control group, especially for the active tuberculosis patients (P<0.01). The peripheral blood CD4/CD8 levels in the static tuberculosis patients was lower than that in the control group, but was significantly higher than that in active tuberculosis patients (P<0.01). The serum IL-1, IL-6, and TNF-α levels in the experiment group were significantly higher than those in the control group, especially for the active tuberculosis patients (P<0.01).Conclusions:The cell subsets and inflammatory cytokines play an important role in patients with pulmonary tuberculosis, whose dynamic change can effectively display the immune function and severity degree, which is of great value in estimating the condition and assessing the prognosis; therefore, it deserves to be further explored in the clinic.

  10. Ex vivo generation of interstitial and Langerhans cell-like dendritic cell subset-based vaccines for hematological malignancies.

    Science.gov (United States)

    Hutten, Tim; Thordardottir, Soley; Hobo, Willemijn; Hübel, Jessica; van der Waart, Anniek B; Cany, Jeannette; Dolstra, Harry; Hangalapura, Basav N

    2014-06-01

    Autologous, patient-specific, monocyte-derived dendritic cell (MoDC) vaccines have been successfully applied in the clinical studies so far. However, the routine application of this strategy has been hampered by the difficulties in generating sufficient numbers of DC and the poor DC vaccine quality because of pathology or prior treatment received by the patients. The immunotherapeutic potential of other subsets of DC has not been thoroughly investigated because of their rarity in tissues and difficulties associated with their ex vivo generation. The high expansion and differentiation potential of CD34 hematopoietic progenitor cells (HPC), isolated from umbilical cord blood (UCB), into different DC subsets make them an attractive alternative DC source for cancer immunotherapy. Therefore, the aim of this study was to generate a large number of different DC subsets from CD34 HPC and evaluate their functionality in comparison with MoDC. Our culture protocol generated a clinically relevant number of mature CD1a myeloid DC and CD207 Langerhans cells (LC)-like DC subsets from CD34 HPC with >95% purity. Both DC subsets exhibited a cytokine profile that favors cytotoxic T-cell responses. Furthermore, UCB-DC and UCB-LC demonstrated superior induction of proliferation of both allogeneic as well as viral antigen-specific CD8 T cells, both in vitro and in vivo. Additional studies revealed that UCC-DC and UCB-LC can efficiently expand minor histocompatibility antigen (MiHA) HA-1-specific cytotoxic T cells in the peripheral blood of leukemia patients and prime MiHA HA-1-specific and HA-2-specific cytotoxic T cells in vitro. These preclinical findings support the pharmaceutical development of the described culture protocol for clinical evaluation.

  11. IL7Rα expression and upregulation by IFNβ in dendritic cell subsets is haplotype-dependent.

    Directory of Open Access Journals (Sweden)

    Fiona C McKay

    Full Text Available The IL7Rα gene is unequivocally associated with susceptibility to multiple sclerosis (MS. Haplotype 2 (Hap 2 confers protection from MS, and T cells and dendritic cells (DCs of Hap 2 exhibit reduced splicing of exon 6, resulting in production of relatively less soluble receptor, and potentially more response to ligand. We have previously shown in CD4 T cells that IL7Rα haplotypes 1 and 2, but not 4, respond to interferon beta (IFNβ, the most commonly used immunomodulatory drug in MS, and that haplotype 4 (Hap 4 homozygotes have the highest risk of developing MS. We now show that IL7R expression increases in myeloid cells in response to IFNβ, but that the response is haplotype-dependent, with cells from homozygotes for Hap 4 again showing no response. This was shown using freshly derived monocytes, in vitro cultured immature and mature monocyte-derived dendritic cells, and by comparing homozygotes for the common haplotypes, and relative expression of alleles in heterozygotes (Hap 4 vs not Hap 4. As for T cells, in all myeloid cell subsets examined, Hap 2 homozygotes showed a trend for reduced splicing of exon 6 compared to the other haplotypes, significantly so in most conditions. These data are consistent with increased signaling being protective from MS, constitutively and in response to IFNβ. We also demonstrate significant regulation of immune response, chemokine activity and cytokine biosynthesis pathways by IL7Rα signaling in IFNβ -treated myeloid subsets. IFNβ-responsive genes are over-represented amongst genes associated with MS susceptibility. IL7Rα haplotype may contribute to MS susceptibility through reduced capacity for IL7Rα signalling in myeloid cells, especially in the presence of IFNβ, and is currently under investigation as a predictor of therapeutic response.

  12. Survival and signaling changes in antigen presenting cell subsets after radiation

    Science.gov (United States)

    Parker, Jennifer Janell

    examine co-stimulatory receptor activation, pro-inflammatory cytokine release, and T cell proliferation with and without radiation and inhibition of the NFkappaB pathway, demonstrated that NEMO is necessary for the activation, maturation, and enhanced responsiveness of human subsets of antigen presenting cells that occur after radiation. These findings provided insight into the mechanism of action of radiation-enhanced promotion of the antigen presenting cell responses. The methods of analysis employed can be used for monitoring immune changes that impact immune modulation in transplantation and tumor vaccines studies. Furthermore, NFkappaB pathway proteins have the potential to serve as biomarkers for optimal antitumor responses. The NBD peptide may also have usefulness as a therapeutic agent for inhibition of graft versus host disease (GVHD) in patients who have undergone transplantation. While the first set of experiments focused on antigen presenting cell responsiveness, the second set of experiments were designed to enhance our understanding of why antigen presenting cells, specifically monocytes and dendritic cells, are more radioresistant than conventional T cells. Flow cytometric analysis of various surface markers and intracellular signaling markers were used to examine the mechanisms behind the radioresistance of antigen presenting cells. The experiments described here showed a hierarchy of radiosensitivity among T cells, with naive CD8 T cells being the most radiosensitive and CD4 memory T cells being the most radioresistant. Antigen presenting cells were found to be significantly more radioresistant than T cell subsets (<10 fold decrease after radiation), and among APC, monocytes were more radiosensitive than either total or conventional dendritic cells. Furthermore APC expressed lower levels of Bax after radiation than T cells, and APC subsets that expressed high levels were also more sensitive to radiation induced cell death. These results demonstrate that T

  13. Identification of new hematopoietic cell subsets with a polyclonal antibody library specific for neglected proteins.

    Directory of Open Access Journals (Sweden)

    Monica Moro

    Full Text Available The identification of new markers, the expression of which defines new phenotipically and functionally distinct cell subsets, is a main objective in cell biology. We have addressed the issue of identifying new cell specific markers with a reverse proteomic approach whereby approximately 1700 human open reading frames encoding proteins predicted to be transmembrane or secreted have been selected in silico for being poorly known, cloned and expressed in bacteria. These proteins have been purified and used to immunize mice with the aim of obtaining polyclonal antisera mostly specific for linear epitopes. Such a library, made of about 1600 different polyclonal antisera, has been obtained and screened by flow cytometry on cord blood derived CD34+CD45dim cells and on peripheral blood derived mature lymphocytes (PBLs. We identified three new proteins expressed by fractions of CD34+CD45dim cells and eight new proteins expressed by fractions of PBLs. Remarkably, we identified proteins the presence of which had not been demonstrated previously by transcriptomic analysis. From the functional point of view, looking at new proteins expressed on CD34+CD45dim cells, we identified one cell surface protein (MOSC-1 the expression of which on a minority of CD34+ progenitors marks those CD34+CD45dim cells that will go toward monocyte/granulocyte differentiation. In conclusion, we show a new way of looking at the membranome by assessing expression of generally neglected proteins with a library of polyclonal antisera, and in so doing we have identified new potential subsets of hematopoietic progenitors and of mature PBLs.

  14. Lymphocyte subsets, dendritic cells and cytokine profiles in mice with melanoma treated with Uncaria tomentosa

    OpenAIRE

    Lozada-Requena, Iván; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú. EMINDES SAC (empresa de investigación y desarrollo en cáncer). Lima, Perú.; Núñez, César; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú. EMINDES SAC (empresa de investigación y desarrollo en cáncer). Lima, Perú.; Alvárez, Yubell; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.; Kahn, Laura; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.; Aguilar, José; Laboratorio de Inmunología. Departamento de Ciencias Celulares y Moleculares. Facultad de Ciencias y Filosofía. Universidad Peruana Cayetano Heredia. Lima, Perú.

    2015-01-01

    Objectives. To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. Materials and methods: Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the pl...

  15. Relationship between Various Chinese Medicine Types and T-cell Subsets in Patients with Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    常廷民; 李秀敏; 赵习德

    2009-01-01

    Objective:To investigate the relationship between various Chinese medicine(CM) types and T-cell subsets(CD4~+ and CD8~+) in the colonic mucous membranes of patients with ulcerative colitis(UC).Methods: Fifty UC patients were enrolled,after differentiation into four types by CM syndromes,i.e.,the internal heat-damp accumulation type(IHDA),the qi-stagnancy with blood stasis type(QSBS),the Pi(脾)-Shen(肾) yang-deficiency type(PSYD) and the yin-blood deficiency type(YBD).From every patient,3-5 pieces of intest...

  16. A hitchhiker's guide to myeloid cell subsets: practical implementation of a novel mononuclear phagocyte classification system

    Directory of Open Access Journals (Sweden)

    Martin eGuilliams

    2015-08-01

    Full Text Available The classification of mononuclear phagocytes as either dendritic cells or macrophages has been mainly based on morphology, the expression of surface markers and assumed functional specialization. We have recently proposed a novel classification system of mononuclear phagocytes based on their ontogeny. Here we discuss the practical application of such a classification system through a number of prototypical examples we have encountered while hitchhiking from one subset to another, across species and between steady state and inflammatory settings. Finally, we discuss the advantages and drawbacks of such a classification system and propose a number of improvements to move from theoretical concepts to concrete guidelines.

  17. Specific subsets of immune cells in human decidua differ between normal pregnancy and preeclampsia - a prospective observational study

    Directory of Open Access Journals (Sweden)

    Rieger Lorenz

    2009-01-01

    Full Text Available Abstract Background Changes in the balance of decidual leucocyte populations may lead to an unfavourable uterine microenvironment which may be associated with the development of preeclampsia (PE. In this study, we therefore investigated the leucocyte subpopulations in decidual tissues of 33 women with preeclampsia and 66 control patients. Methods Decidua was either obtained via curettage during cesarean section or dissected from the surface of the basal plate of the placenta after spontaneous delivery. We used FACS analysis to quantify decidual leukocytes (CD45, NK cells (CD56+/CD16+ and CD56++/CD16-, antigen presenting cells (HLA-DR, DC-Sign, CD14 and T/B cells (CD8, CD4, alpha-beta-T-cell receptor, gamma-delta-T-cell receptor, CD25, CD19. Results The number of decidual cytotoxic CD8+T-lymphocytes (P < 0.02, alpha-beta -T-cell receptor positive T cells (P < 0.03 and of CD56+/CD16+ NK cells (P < 0.03 was lower in decidua from women with PE than in decidua from control patients. Conclusion The observed reduction of specific leucocyte subsets could create a microenvironment which is unfavourable for an appropriate placentation and could thereby be involved in the development of preeclamptic symptoms.

  18. In vitro donor-specific hyporesponsiveness and T cell subsets in renal allograft recipients.

    Science.gov (United States)

    Bas, J; Mestre, M; Griñó, J M; Massip, E; Castelao, A M; Romeu, A; González, L; Valls, A; Buendía, E

    1993-01-01

    In order to assess the immune mechanisms triggered by an immunosuppressive regimen consisting of prophylactic antilymphocyte globulin plus low-dose cyclosporine A and steroids, we studied the short-term evolution of both, anti donor in vitro alloresponse and peripheral blood T cell subsets in 21 recipients of a cadaveric kidney allograft. Spleen cells from cadaveric donors and peripheral blood lymphocytes from the respective recipients pretransplant (pre-Tx), at three and six months posttransplant (post-Tx) were obtained to perform one-way mixed lymphocyte cultures and flow cytometry analysis of lymphocyte subsets. The results indicated the development of donor-specific mixed lymphocyte culture (MLC) hyporesponsiveness as early as three months post-Tx, paralleled by a decrease in CD4+CD29+ helper-inducer cells and by an increase in CD8+CD45RA+ suppressor lymphocytes in peripheral blood. These changes were reflected in a very good clinical outcome of the patients. The present results further suggest that suppression of the immune system just before transplantation is a suitable method to induce early specific hyporesponsiveness to the allograft.

  19. Teratogens induce a subset of small heat shock proteins in Drosophila primary embryonic cell cultures.

    Science.gov (United States)

    Buzin, C H; Bournias-Vardiabasis, N

    1984-01-01

    Drosophila embryonic cells placed into culture just after gastrulation differentiate in vitro over the next 24 hr. A number of drugs that are teratogenic in mammalian systems have been found to inhibit muscle or neuron differentiation (or both) in these developing cultures. We have examined, by two-dimensional gel electrophoresis, the effects of these drugs on protein synthesis in embryonic cells. For nine teratogens tested, cells treated for 20 hr with the drug show a dramatic induction of three proteins of about 20 kilodaltons, in addition to the normal proteins synthesized by untreated cells. Three teratogens as well as all eight nonteratogens tested did not show this induction. The induced proteins appear to be identical to three of the heat shock proteins (hsp 23, 22a, and 22b), as shown by electrophoretic mobilities and peptide mapping by partial proteolysis. A 37 degrees C heat shock of the embryonic cells produces the full complement of heat shock proteins, whereas drug-treated cells induce only the subset hsp 23, 22a, and 22b but not hsp 26 or 27. beta-Ecdysterone, the Drosophila molting hormone, also inhibits embryonic differentiation and induces hsp 23, 22a, and 22b, a partial subset of the heat shock proteins (hsp 22, 23, 26, and 27) induced by the hormone in imaginal discs and some Drosophila continuous cell lines. Dose-response studies of several drugs show a correlation between the degree of inhibition of differentiation and the level of induction of hsp 23, 22a, and 22b. The induction of heat shock proteins by drugs may reflect specific types of stress that can also give rise to teratogenesis. Images PMID:6588379

  20. Notch reporter activity in breast cancer cell lines identifies a subset of cells with stem cell activity.

    Science.gov (United States)

    D'Angelo, Rosemarie C; Ouzounova, Maria; Davis, April; Choi, Daejin; Tchuenkam, Stevie M; Kim, Gwangil; Luther, Tahra; Quraishi, Ahmed A; Senbabaoglu, Yasin; Conley, Sarah J; Clouthier, Shawn G; Hassan, Khaled A; Wicha, Max S; Korkaya, Hasan

    2015-03-01

    Developmental pathways such as Notch play a pivotal role in tissue-specific stem cell self-renewal as well as in tumor development. However, the role of Notch signaling in breast cancer stem cells (CSC) remains to be determined. We utilized a lentiviral Notch reporter system to identify a subset of cells with a higher Notch activity (Notch(+)) or reduced activity (Notch(-)) in multiple breast cancer cell lines. Using in vitro and mouse xenotransplantation assays, we investigated the role of the Notch pathway in breast CSC regulation. Breast cancer cells with increased Notch activity displayed increased sphere formation as well as expression of breast CSC markers. Interestingly Notch(+) cells displayed higher Notch4 expression in both basal and luminal breast cancer cell lines. Moreover, Notch(+) cells demonstrated tumor initiation capacity at serial dilutions in mouse xenografts, whereas Notch(-) cells failed to generate tumors. γ-Secretase inhibitor (GSI), a Notch blocker but not a chemotherapeutic agent, effectively targets these Notch(+) cells in vitro and in mouse xenografts. Furthermore, elevated Notch4 and Hey1 expression in primary patient samples correlated with poor patient survival. Our study revealed a molecular mechanism for the role of Notch-mediated regulation of breast CSCs and provided a compelling rationale for CSC-targeted therapeutics.

  1. Trans-active factors controlling the IL-2 gene in adult human T-cell subsets

    Directory of Open Access Journals (Sweden)

    A. Mouzaki

    1992-01-01

    Full Text Available IL-2 secretion in total or subsets of PHA/PMA-stimulated PBMC-derived human T-lymphocytes was monitored and found to be largely due to CD4+CD8− cells. The presence and functional state of transcription factors (TF was assessed by protein-DNA interaction assays and functional transactivation experiments in the Xenopts oocyte system, modulating IL-2 transcription by injection of proteins. The results reveal that CD4+CD8− cells contain both, functional silencer in their resting, and positive TF in their activated states while the CD4+CD8− group contains only non-functional positive TF. This demonstrates that the on/off switch of IL-2 transcription is based on the same mechanism in primary T-lymphocytes of mouse spleen and in peripheral human CD4+CD8− cells.

  2. Binding of peanut lectin to germinal-centre cells: a marker for B-cell subsets of follicular lymphoma?

    OpenAIRE

    De Rose, M L; Habeshaw, J A; R. Kennedy; Sloane, J.; Wiltshaw, E; Davies, A. J.

    1981-01-01

    The binding of horseradish-peroxidase-labelled peanut lectin (HRP-PNL) to cryostat sections of tonsil, lymphoma lymph nodes, reactive lymph nodes and miscellaneous tumours demonstrated that PNL binds selectively to lymphocytes in germinal centres. Lymph nodes from 21 patients with non-Hodgkin's lymphomas were phenotyped as cell suspensions for PNL binding, and the following surface markers: E rosetting, C3d, SIg, OK markers of T-cell subsets, Ig heavy-chain and light-chain classes. There was ...

  3. The role of T cell subsets and cytokines in the regulation of intracellular bacterial infection

    Directory of Open Access Journals (Sweden)

    Oliveira S.C.

    1998-01-01

    Full Text Available Cellular immune responses are a critical part of the host's defense against intracellular bacterial infections. Immunity to Brucella abortus crucially depends on antigen-specific T cell-mediated activation of macrophages, which are the major effectors of cell-mediated killing of this organism. T lymphocytes that proliferate in response to B. abortus were characterized for phenotype and cytokine activity. Human, murine, and bovine T lymphocytes exhibited a type 1 cytokine profile, suggesting an analogous immune response in these different hosts. In vivo protection afforded by a particular cell type is dependent on the antigen presented and the mechanism of antigen presentation. Studies using MHC class I and class II knockout mice infected with B. abortus have demonstrated that protective immunity to brucellosis is especially dependent on CD8+ T cells. To target MHC class I presentation we transfected ex vivo a murine macrophage cell line with B. abortus genes and adoptively transferred them to BALB/c mice. These transgenic macrophage clones induced partial protection in mice against experimental brucellosis. Knowing the cells required for protection, vaccines can be designed to activate the protective T cell subset. Lastly, as a new strategy for priming a specific class I-restricted T cell response in vivo, we used genetic immunization by particle bombardment-mediated gene transfer

  4. A unique dermal dendritic cell subset that skews the immune response toward Th2.

    Directory of Open Access Journals (Sweden)

    Ryuichi Murakami

    Full Text Available Dendritic cell (DC subsets in the skin and draining lymph nodes (LNs are likely to elicit distinct immune response types. In skin and skin-draining LNs, a dermal DC subset expressing macrophage galactose-type C-type lectin 2 (MGL2/CD301b was found distinct from migratory Langerhans cells (LCs or CD103(+ dermal DCs (dDCs. Lower expression levels of Th1-promoting and/or cross-presentation-related molecules were suggested by the transcriptome analysis and verified by the quantitative real-time PCR analysis in MGL2(+ dDCs than in CD103(+ dDCs. Transfer of MGL2(+ dDCs but not CD103(+ dDCs from FITC-sensitized mice induced a Th2-type immune response in vivo in a model of contact hypersensitivity. Targeting MGL2(+ dDCs with a rat monoclonal antibody against MGL2 efficiently induced a humoral immune response with Th2-type properties, as determined by the antibody subclass. We propose that the properties of MGL2(+ dDCs, are complementary to those of CD103(+ dDCs and skew the immune response toward a Th2-type response.

  5. Effect of immunoglobulin on T cell subsets and inflammatory cytokines of patients with viral meningoencephalitis

    Institute of Scientific and Technical Information of China (English)

    Zhi-Cheng Bao; Xue-Long Xia; Ya-Ping Wu; Dan Liu

    2016-01-01

    Objective:To observe the effect of immunoglobulin in the adjuvant therapy of viral meningoencephalitis (VM).Methods: A total of 78 cases of VN in our hospital from September 2011 to April 2016 were chosen. According to the admission order, they were randomly divided into two groups, the control group and observation group, and 39 cases in each group. The control group was treated with acyclovir conventional therapy, and the observation group was supplemented by immunoglobulins. The differences of serum and cerebrospinal fluid levels of T cell subsets and inflammatory cytokines between the two groups before and after treatment were compared.Results:The total effective rate of the observation group was significantly higher than that in the control group (P<0.05). The serum and cerebrospinal fluid levels of T cell subsets CD3+, CD4+ and CD4+/CD8+ were significantly higher than those in the control group, while the CD8+ was lower than that in the control group (P<0.05). The serum and cerebrospinal fluid levels of inflammatory cytokines PCT, INF-γ, IL-6 and TNF-α were all significantly lower than those in the control group (P<0.05).Conclusions:Immunoglobulin can effectively improve the level of CD3+, CD4+ and VM in CD8 patients, and adjust the CD4/CD8 balance, inhibit synthesis and secretion of Th1cytokines, so to play the assistant effects of acyclovir in the treatment of VM.

  6. Cellular prion protein is expressed in a subset of neuroendocrine cells of the rat gastrointestinal tract.

    Science.gov (United States)

    Marcos, Zuberoa; Pffeifer, Kristine; Bodegas, María E; Sesma, María P; Guembe, Laura

    2004-10-01

    Prion diseases are believed to develop from the conformational change of normal cellular prion protein (PrPc) to a pathogenic isoform (PrPsc). PrPc is present in both the central nervous system and many peripheral tissues, although protein concentration is significantly lower in non-neuronal tissues. PrPc expression is essential for internalization and replication of the infectious agent. Several works have pointed to the gastrointestinal (GI) tract as the principal site of entry of PrPsc, but how passage through the GI mucosa occurs is not yet known. Here we studied PrPc expression using Western blot, RT-PCR, and immunohistochemistry in rat GI tract. PrPc mRNA and protein were detected in corpus, antrum, duodenum, and colon. Immunoreactivity was found in scattered cells of the GI epithelium. With double immunofluorescence, these cells have been identified as neuroendocrine cells. PrPc immunostaining was found in subsets of histamine, somatostatin (Som), ghrelin, gastrin (G), and serotonin (5HT) cells in stomach. In small and large bowel, PrPc cells co-localized with subpopulations of 5HT-, Som-, G-, and peptide YY-immunolabeled cells. Our results provide evidence for a possible and important role of endocrine cells in the internalization of PrPsc from gut lumen.

  7. Distinct Functions of Specialized Dendritic Cell Subsets in Atherosclerosis and the Road Ahead

    Directory of Open Access Journals (Sweden)

    Alma Zernecke

    2014-01-01

    Full Text Available Atherosclerotic vascular disease is modulated by immune mechanisms. Dendritic cells (DCs and T cells are present within atherosclerotic lesions and function as central players in the initiation and modulation of adaptive immune responses. In previous years, we have studied the functional contribution of distinct DC subsets in disease development, namely, that of CCL17-expressing DCs as well as that of plasmacytoid DCs that play specialized roles in disease development. This review focuses on important findings gathered in these studies and dissects the multifaceted contribution of CCL17-expressing DCs and pDCs to the pathogenesis of atherosclerosis. Furthermore, an outlook on future challenges faced when studying DCs in this detrimental disease are provided, and hurdles that will need to be overcome in order to enable a better understanding of the contribution of DCs to atherogenesis are discussed, a prerequisite for their therapeutic targeting in atherosclerosis.

  8. Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people

    Directory of Open Access Journals (Sweden)

    Özcelik Dennis

    2008-07-01

    Full Text Available Abstract Background T cell-mediated immunity in elderly people is compromised in ways reflected in the composition of the peripheral T cell pool. The advent of polychromatic flow cytometry has made analysis of cell subsets feasible in unprecedented detail. Results Here we document shifts in subset distribution within naïve (N, central memory (CM and effector memory (EM cells defined by CD45RA and CCR7 expression in the elderly, additionally using the costimulatory receptors CD27 and CD28, as well as the coinhibitory receptors CD57 and KLRG-1, to further dissect these. Although differences between young and old were more marked in CD8 than in CD4 cells, a similar overall pattern prevailed in both. Thus, the use of all these markers together, and inclusion of assays of proliferation and cytokine secretion, may enable the construction of a differentiation scheme applicable to CD4 as well as CD8 cells, with the model (based on Romero et al. suggesting the progression N→CM→EM1→EM2→pE1→pE2→EM4→EM3→E end-stage non-proliferative effector cells. Conclusion Overall, the results suggest that both differences in subset distribution and differences between subsets are responsible for age-related changes in CD8 cells but that differences within rather than between subsets are more prominent for CD4 cells.

  9. Perturbations of Monocyte Subsets and Their Association with T Helper Cell Differentiation in Acute and Chronic HIV-1-Infected Patients

    Science.gov (United States)

    Chen, Peng; Su, Bin; Zhang, Tong; Zhu, Xiaojing; Xia, Wei; Fu, Yan; Zhao, Guoxian; Xia, Huan; Dai, Lili; Sun, Lijun; Liu, Lifeng; Wu, Hao

    2017-01-01

    Monocytes have been recently subdivided into three subsets: classical (CD14++CD16−), intermediate (CD14++CD16+), and non-classical (CD14+CD16++) subsets, but phenotypic and functional abnormalities of the three monocyte subsets in HIV-1 infection have not been fully characterized, especially in acute HIV-1 infection (AHI). In the study, we explored the dynamic changes of monocyte subsets and their surface markers, and the association between monocyte subsets and the IFN-γ, interleukin (IL)-4, IL-17, and TNF-α producing CD4+ T cells in acute and chronic HIV-1-infected patients. We found that, in the acute HIV-1-infected individuals, the frequency of the intermediate CD14++CD16+ monocyte subsets, the CD163 density and HLA-DR density on intermediate CD14++CD16+ monocytes, and plasma soluble form of CD163 (sCD163) were significantly higher than that in healthy controls. Intermediate CD14++CD16+ monocyte subsets and their HLA-DR expression levels were inversely correlated with the CD4+ T cell counts, and the intermediate CD14++CD16+ monocytes were positively correlated with plasma sCD163. In contrast to the non-classical CD14+CD16++ and classical CD14++CD16− monocyte subsets, the frequency of the intermediate CD14++CD16+ monocytes was positively associated with the frequency of IFN-γ and IL-4 producing CD4+ T cells in HIV-1-infected patients. Taken together, our observations provide new insight into the roles of the monocyte subsets in HIV pathogenesis, particularly during AHI, and our findings may be helpful for the treatment of HIV-related immune activation.

  10. Clinical characteristics and peripheral T cell subsets in Parkinson's disease patients with constipation.

    Science.gov (United States)

    Chen, Yuhua; Yu, Meiling; Liu, Xiaolin; Qu, Hongdang; Chen, Qiming; Qian, Weidong; Wei, Daoxiang; Xu, Wenfang; Ma, Bo; Wu, Wei

    2015-01-01

    Constipation is frequently reported in Parkinson's disease (PD). We evaluated the characteristics of patients with PD and constipation and explored the role of T cell subsets in PD-associated constipation. One hundred and two patients with PD treated at the First Affiliated Hospital of Bengbu Medical College were enrolled in this study between January 2012 and October 2013. All patients completed KESS questionnaires and constipation was rated. The proportions of peripheral blood Thl7 and Treg cells were assessed by flow cytometry in 45 patients. Colonoscopies were performed in six patients. Thirty-one patients with PD reported slow-transit constipation (STC), 15 rectal evacuation disorder (RED) and 33 mixed constipation (Mixed). STC most frequently occurred before onset of PD motor symptoms, while Mixed occurred before or after motor symptoms, and RED occurred most frequently after motor symptoms. CD4+ T cell infiltration in the colonic mucosa was observed in patients with PD and constipation. The frequency of Th17 and Treg cells in patients with PD and constipation was significantly higher than in those without constipation (Pconstipation, the frequency of Th17 and Treg cells in STC was the highest. However, there was no difference in the ratio of Th17/Tregs between the patients with PD with and without constipation, or patients with PD and different types of constipations (P>0.05). Constipation reported before the onset of PD motor symptoms was most often STC or Mixed, and PD constipation may be associated with immune activation in the colonic mucosa.

  11. Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis.

    Directory of Open Access Journals (Sweden)

    Kerstin Trautwein-Weidner

    2015-10-01

    Full Text Available Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated a Candida-specific TCR transgenic mouse reactive to a novel endogenous antigen that is conserved in multiple distant species of Candida, including the clinically highly relevant C. albicans and C. glabrata. Using TCR transgenic T cells in combination with an experimental model of oropharyngeal candidiasis (OPC we investigated antigen presentation and Th17 priming by different subsets of dendritic cells (DCs present in the infected oral mucosa. Candida-derived endogenous antigen accesses the draining lymph nodes and is directly presented by migratory DCs. Tissue-resident Flt3L-dependent DCs and CCR2-dependent monocyte-derived DCs collaborate in antigen presentation and T cell priming during OPC. In contrast, Langerhans cells, which are also present in the oral mucosa and have been shown to prime Th17 cells in the skin, are not required for induction of the Candida-specific T cell response upon oral challenge. This highlights the functional compartmentalization of specific DC subsets in different tissues. These data provide important new insights to our understanding of tissue-specific antifungal immunity.

  12. Gamma-secretase inhibition combined with platinum compounds enhances cell death in a large subset of colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Feller Stephan M

    2008-10-01

    Full Text Available Abstract Background Notch signalling is essential for the development and maintenance of the colonic epithelium. Its inhibition induces a differentiation phenotype in vivo and reduces adenomas in APCmin mice. Whether Notch signals are also required in colorectal cancer (CRC has remained elusive. Therefore, 64 CRC cell lines were analysed for the occurrence of proteolytically processed, active Notch. Results 63 CRC lines contained a fragment with approximately the size of the Notch1 intracellular domain (NICD, which is required for signalling. Subsequent analyses with an antibody that specifically recognises the free Val1744 residue generated by γ-secretase-mediated cleavage of Notch1 showed that a subset of CRC cells lacks this specific Val1744-NICD. Surprisingly, inhibition of Val1744-NICD signalling with different γ-secretase inhibitors (GSI did not lead to substantial effects on CRC cell line growth or survival. However, transient activation of Erk upon GSI treatment was detected. Since cisplatin relies on Erk activation for bioactivity in some cells, platinum compounds were tested together with GSI and enhanced cell killing in a subset of Val1744-NICD-positive CRC cell lines was detected. Erk inhibition ablated this combination effect. Conclusion We conclude that γ-secretase inhibition results in activation of the MAP kinases Erk1/2 and, when used in conjunction, enhances cell death induced by platinum compounds in a large subset of colorectal cancer cell lines. Furthermore the activation of Erk appears to be of particular importance in mediating the enhanced effect seen, as its inhibition abrogates the observed phenomenon. These findings do not only highlight the importance of signalling pathway crosstalk but they may also suggest a new avenue of combination therapy for some colorectal cancers.

  13. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors

    Science.gov (United States)

    Sutton, Lesley-Ann; Young, Emma; Baliakas, Panagiotis; Hadzidimitriou, Anastasia; Moysiadis, Theodoros; Plevova, Karla; Rossi, Davide; Kminkova, Jana; Stalika, Evangelia; Pedersen, Lone Bredo; Malcikova, Jitka; Agathangelidis, Andreas; Davis, Zadie; Mansouri, Larry; Scarfò, Lydia; Boudjoghra, Myriam; Navarro, Alba; Muggen, Alice F.; Yan, Xiao-Jie; Nguyen-Khac, Florence; Larrayoz, Marta; Panagiotidis, Panagiotis; Chiorazzi, Nicholas; Niemann, Carsten Utoft; Belessi, Chrysoula; Campo, Elias; Strefford, Jonathan C.; Langerak, Anton W.; Oscier, David; Gaidano, Gianluca; Pospisilova, Sarka; Davi, Frederic; Ghia, Paolo; Stamatopoulos, Kostas; Rosenquist, Richard

    2016-01-01

    We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (BIRC3, MYD88, NOTCH1, SF3B1 and TP53) and cytogenetic aberrations, we reveal a subset-biased acquisition of gene mutations. More specifically, the frequency of NOTCH1 mutations was found to be enriched in subsets expressing unmutated immunoglobulin genes, i.e. #1, #6, #8 and #59 (22–34%), often in association with trisomy 12, and was significantly different (Pimmunoglobulin genes). Interestingly, subsets harboring a high frequency of NOTCH1 mutations were found to carry few (if any) SF3B1 mutations. This starkly contrasts with subsets #2 and #3 where, despite their immunogenetic differences, SF3B1 mutations occurred in 45% and 46% of cases, respectively. In addition, mutations within TP53, whilst enriched in subset #1 (16%), were rare in subsets #2 and #8 (both 2%), despite all being clinically aggressive. All subsets were negative for MYD88 mutations, whereas BIRC3 mutations were infrequent. Collectively, this striking bias and skewed distribution of mutations and cytogenetic aberrations within specific chronic lymphocytic leukemia subsets implies that the mechanisms underlying clinical aggressiveness are not uniform, but rather support the existence of distinct genetic pathways of clonal evolution governed by a particular stereotyped B-cell receptor selecting a certain molecular lesion(s). PMID:27198719

  14. Circulating subsets and CD4(+)CD25(+) regulatory T cell function in chronic inflammatory demyelinating polyradiculoneuropathy.

    Science.gov (United States)

    Sanvito, Lara; Makowska, Anna; Gregson, Norman; Nemni, Raffaello; Hughes, Richard A C

    2009-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory disease of the peripheral nervous system that is probably autoimmune in origin. Different components of the adaptive and innate immunity may be responsible for the aberrant response towards nerve antigens. To investigate this, we examined lymphocyte subsets and regulatory T cell (Treg) function in the blood of CIDP patients, healthy controls (HC) and subjects with non-immune mediated neuropathies (other neuropathies, ON). We used flow cytometry to determine the frequency of monocytes, B cells, natural killer (NK) and NK-T cells, total and activated CD4(+) and CD8(+) T cells, effector memory and central memory CD4(+) and CD8(+) T cells, and CD4(+)CD25(high)Foxp3(+) Tregs. Treg function was studied after polyclonal stimulation and antigen specific stimulation with myelin protein peptides in CIDP and HC. There was an increased frequency of monocytes (p = 0.02) and decreased frequency of NK cells (p = 0.02) in CIDP compared with HC but not ON. There were no significant differences in other populations. Treg function was impaired in CIDP compared to HC (p = 0.02), whilst T cell proliferation to myelin protein peptides before and after depletion of Tregs was not different between patients and controls. This study shows increased circulating monocytes and reduced NK cells in CIDP. Although Treg frequency was not altered, we confirm that Tregs display a defect of suppressive function. Myelin protein peptides were not the target of the altered peripheral regulation of the immune response. The mechanisms of peripheral immune tolerance in CIDP and their relevance to the pathogenesis deserve further exploration.

  15. The Effect of BCG-PSN on T-cell Subsets and Cytokines in Vernal Conjunctivitis

    Institute of Scientific and Technical Information of China (English)

    胡军; 陈欢

    2002-01-01

    The effects of BCG-PSN on T-cell subsets and cytokines in vernal conjunctivitis were observed. The level of total IgE was quantitatively determined before and after treatment with BCGPSN by allergen diagnostic instrument in vitro. The content of T-cell subsets of peripheral blood and cytokine were determined by using indirect immune fluorescence method, and IL-4 and INF-γ were quantified by ELISA. The results showed that the level of total IgE was substantially reduced (P<0.01) after treatment in the BCG-PSN group. Meanwhile, CD8+ was decreased, CD4+ and CD4+/CD8+ratio elevated with significant differences (P<0. 05) as compared with pre-treatment results. The changes in total IgE, CD+8 ,CD4+ and CD4+/CD+8 ratio after treatment also presented significant differences (P<0. 05) between BCG-PSN group and routine treatment group. The level of IL-4 in serum declined (P<0. 05) after treatment in the BCG-PSN group, and INF-γ went up (P<0.05). IL-4and INF-γ in serum showed significant differences (P<0. 05) between two groups after treatment.It is concluded that BCG-PSN has a bi-directional immunoregulating effect. It can bring CD4+ and CD+8- into homeostasis, thereby preventing the occurrence of anaphylaxis. At the same time, BCGPSN can restrain Th2, decrease the synthesis of IL-4, switch the balance of Th1/Th2 to Th1 side,boost up the predominance of Th1 relatively, which is propitious to perennial stabilization and recov cry of vernal conjunctivitis.

  16. The role of dendritic cell subsets and innate immunity in the pathogenesis of type 1 diabetes and other autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Jeffrey D. Price

    2015-06-01

    Full Text Available Dendritic cells (DCs are key antigen presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, there are 4 main subsets identified in both mouse and human: conventional cDC1 and cDC2, plasmacytoid DCs, and monocyte-derived DCs. In this review, we will discuss the role of these subsets in autoimmune pathogenesis and regulation, as well as the genetic and environmental signals that influence their function. Specific topics to be addressed include: impact of susceptibility loci on DC subsets, alterations in DC subset development, the role of infection- and host-derived innate inflammatory signals, and the role of the intestinal microbiota on DC phenotype. The effects of these various signals on disease progression and the relative effects of DC subset composition and maturation level of DCs will be examined. These areas will be explored using examples from several autoimmune diseases but will focus mainly on type 1 diabetes.

  17. T Cell Subset and Stimulation Strength-Dependent Modulation of T Cell Activation by Kv1.3 Blockers

    Science.gov (United States)

    Fung-Leung, Wai-Ping; Edwards, Wilson; Liu, Yi; Ngo, Karen; Angsana, Julianty; Castro, Glenda; Wu, Nancy; Liu, Xuejun; Swanson, Ronald V.; Wickenden, Alan D.

    2017-01-01

    Kv1.3 is a voltage-gated potassium channel expressed on T cells that plays an important role in T cell activation. Previous studies have shown that blocking Kv1.3 channels in human T cells during activation results in reduced calcium entry, cytokine production, and proliferation. The aim of the present study was to further explore the effects of Kv1.3 blockers on the response of different human T cell subsets under various stimulation conditions. Our studies show that, unlike the immune suppressor cyclosporine A, the inhibitory effect of Kv1.3 blockers was partial and stimulation strength dependent, with reduced inhibitory efficacy on T cells under strengthened anti-CD3/CD28 stimulations. T cell responses to allergens including house dust mites and ragweed were partially reduced by Kv1.3 blockers. The effect of Kv1.3 inhibition was dependent on T cell subsets, with stronger effects on CCR7- effector memory compared to CCR7+ central memory CD4 T cells. Calcium entry studies also revealed a population of CD4 T cells resistant to Kv1.3 blockade. Activation of CD4 T cells was accompanied with an increase in Kv1.3 currents but Kv1.3 transcripts were found to be reduced, suggesting a posttranscriptional mechanism in the regulation of Kv1.3 activities. In summary, Kv1.3 blockers inhibit T cell activation in a manner that is highly dependent on the T cell identity and stimulation strength, These findings suggest that Kv1.3 blockers inhibit T cells in a unique, conditional manner, further refining our understanding of the therapeutic potential of Kv1.3 blockers. PMID:28107393

  18. Characterization of a naturally occurring breast cancer subset enriched in EMT and stem cell characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Hennessy, Bryan T.; Gonzalez-Angulo, Ana-Maria; Stemke-Hale, Katherine; Gilcrease, Michael Z.; Krishnamurthy, Savitri; Lee, Ju-Seog; Fridlyand, Jane; Sahin, Aysegul; Agarwal, Roshan; Joy, Corwin; Liu, Wenbin; Stivers, David; Baggerly, Keith; Carey, Mark; Lluch, Ana; Monteagudo, Carlos; He, Xiaping; Weigman, Victor; Fan, Cheng; Palazzo, Juan; Hortobagyi, Gabriel N.; Nolden, Laura K.; Wang, Nicholas J.; Valero, Vicente; Gray, Joe W.; Perou, Charles M.; Mills, Gordon B.

    2009-05-19

    Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor-positive cancers (34.5%; P = 0.32), 17 of 75 HER-2-positive samples (22.7%; P = 0.04), 20 of 240 basal-like cancers (8.3%; P < 0.0001), and 0 of 14 claudin-low tumors (P = 0.004). Of 7 phosphatidylinositol 3-kinase/AKT pathway phosphorylation sites, 6 were more highly phosphorylated in MBCs than in other breast tumor subtypes. The majority of MBCs displayed mRNA profiles different from those of the most common, including basal-like cancers. By transcriptional profiling, MBCs and the recently identified claudin-low breast cancer subset constitute related receptor-negative subgroups characterized by low expression of GATA3-regulated genes and of genes responsible for cell-cell adhesion with enrichment for markers linked to stem cell function and epithelial-to-mesenchymal transition (EMT). In contrast to other breast cancers, claudin-low tumors and most MBCs showed a significant similarity to a 'tumorigenic' signature defined using CD44{sup +}/CD24{sup -} breast tumor-initiating stem cell-like cells. MBCs and claudin-low tumors are thus enriched in EMT and stem cell-like features, and may arise from an earlier, more chemoresistant breast epithelial precursor than basal-like or luminal cancers. PIK3CA mutations, EMT, and stem cell-like characteristics likely contribute to the poor outcomes of MBC and suggest novel therapeutic targets.

  19. From the regulatory functions of B cells to the identification of cytokine-producing plasma cell subsets.

    Science.gov (United States)

    Dang, Van Duc; Hilgenberg, Ellen; Ries, Stefanie; Shen, Ping; Fillatreau, Simon

    2014-06-01

    B lymphocytes have a unique role as antibody-producing cells. Antibodies are key mediators of humoral immunity against infections, and are thought to account for the protection afforded by successful vaccines. B cells can also secrete cytokines and subsequently regulate immune responses mediated by T and innate cells. Remarkably, recent studies identified plasma blasts/plasma cells as the main types of activated B cells producing the cytokines interleukin (IL)-10, IL-35, tumor necrosis factor (TNF)-α, IL-17, and GM-CSF in various contexts in mice. Here, we discuss these observations, which suggest the existence of various subsets of plasma blast/plasma cells distinguishable through their cytokine expression pattern.

  20. Analysis of the In Vivo Turnover of CD4+ T-Cell Subsets in Chronically SIV-Infected Sooty Mangabeys.

    Science.gov (United States)

    Ortiz, Alexandra M; Carnathan, Diane G; Yu, Joana; Sheehan, Katherine M; Kim, Peter; Reynaldi, Arnold; Vanderford, Thomas H; Klatt, Nichole R; Brenchley, Jason M; Davenport, Miles P; Silvestri, Guido

    2016-01-01

    Aberrant turnover of memory CD4+ T-cells is central to Acquired Immunodeficiency Syndrome (AIDS) progression. Understanding the relationship between the turnover of CD4+ subsets and immunological homeostasis during simian immunodeficiency virus (SIV) infection in natural hosts may provide insight into mechanisms of immune regulation that may serve as models for therapeutic intervention in Human Immunodeficiency Virus (HIV)-infected persons. Sooty mangabeys (SMs) have naturally evolved with SIV to avoid AIDS progression while maintaining healthy peripheral CD4+ T-cell counts and thus represent a model by which therapeutic interventions for AIDS progression might be elucidated. To assess the relationship between the turnover of CD4+ subsets and immunological homeostasis during SIV infection in non-progressive hosts, we treated 6 SIV-uninfected and 9 SIV-infected SMs with 2'-bromo-5'-deoxyuridine (BrdU) for 14 days and longitudinally assessed CD4+ T-cell subset turnover by polychromatic flow cytometry. We observed that, in SIV-infected SMs, turnover of CD4+ T-cell naïve and central, transitional, and effector memory subsets is comparable to that in uninfected animals. Comparable turnover of CD4+ T-cell subsets irrespective of SIV-infection status likely contributes to the lack of aberrant immune activation and disease progression observed after infection in non-progressive hosts.

  1. Analysis of the In Vivo Turnover of CD4+ T-Cell Subsets in Chronically SIV-Infected Sooty Mangabeys.

    Directory of Open Access Journals (Sweden)

    Alexandra M Ortiz

    Full Text Available Aberrant turnover of memory CD4+ T-cells is central to Acquired Immunodeficiency Syndrome (AIDS progression. Understanding the relationship between the turnover of CD4+ subsets and immunological homeostasis during simian immunodeficiency virus (SIV infection in natural hosts may provide insight into mechanisms of immune regulation that may serve as models for therapeutic intervention in Human Immunodeficiency Virus (HIV-infected persons. Sooty mangabeys (SMs have naturally evolved with SIV to avoid AIDS progression while maintaining healthy peripheral CD4+ T-cell counts and thus represent a model by which therapeutic interventions for AIDS progression might be elucidated. To assess the relationship between the turnover of CD4+ subsets and immunological homeostasis during SIV infection in non-progressive hosts, we treated 6 SIV-uninfected and 9 SIV-infected SMs with 2'-bromo-5'-deoxyuridine (BrdU for 14 days and longitudinally assessed CD4+ T-cell subset turnover by polychromatic flow cytometry. We observed that, in SIV-infected SMs, turnover of CD4+ T-cell naïve and central, transitional, and effector memory subsets is comparable to that in uninfected animals. Comparable turnover of CD4+ T-cell subsets irrespective of SIV-infection status likely contributes to the lack of aberrant immune activation and disease progression observed after infection in non-progressive hosts.

  2. Cross-talk between human dendritic cell subsets influences expression of RNA sensors and inhibits picornavirus infection.

    NARCIS (Netherlands)

    Kramer, M.; Schulte, B.M.; Eleveld-Trancikova, D.; Hout-Kuijer, M.A. van; Toonen, L.W.J.; Tel, J.; Vries, I.J.M. de; Kuppeveld, F.J.M. van; Jansen, B.J.H.; Adema, G.J.

    2010-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells that provide a link between innate and adaptive immunity. Multiple DC subsets exist and their activation by microorganisms occurs through binding of conserved pathogen-derived structures to so-called pattern recognition receptors (PRRs)

  3. NCR1 Expression Identifies Canine Natural Killer Cell Subsets with Phenotypic Similarity to Human Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Jennifer Ann Foltz

    2016-11-01

    Full Text Available Canines spontaneously develop many cancers similar to humans - including osteosarcoma, leukemia, and lymphoma - offering the opportunity to study immune therapies in a genetically heterogeneous and immunocompetent environment. However, a lack of antibodies recognizing canine NK cell markers has resulted in suboptimal characterization and unknown purity of NK cell products, hindering the development of canine models of NK cell adoptive immunotherapy. To this end, we generated a novel antibody to canine NCR1 (NKp46, the putative species-wide marker of NK cells, enabling purification of NK cells for further characterization. We demonstrate that CD3-/NKp46+ cells in healthy and osteosarcoma-bearing canines have phenotypic similarity to human CD3-/NKp46+ NK cells, expressing mRNA for CD16 and the natural cytotoxicity receptors NKp30, NKp44, and NKp80. Functionally, we demonstrate with the calcein release assay that canine CD3-/NKp46+ cells kill canine tumor cell lines without prior sensitization and secrete IFN-γ, TNF-α, IL-8, IL-10, and GM-CSF as measured by Luminex. Like human NK cells, CD3-/NKp46+ cells expand rapidly on feeder cells expressing 4-1BBL and membrane-bound IL-21 (median= 20,283-fold in 21 days. Further, we identify a minor Null population (CD3-/CD21-/CD14-/NKp46- with reduced cytotoxicity against osteosarcoma cells, but similar cytokine secretion as CD3-/NKp46+ cells. Null cells in canines and humans have reduced expression of NKG2D, NKp44, and CD16 compared to NKp46+ NK cells, and can be induced to express NKp46 with further expansion on feeder cells. In conclusion, we have identified and characterized canine NK cells, including an NKp46- subset of canine and human NK cells, using a novel anti-canine NKp46 antibody, and report robust ex vivo expansion of canine NK cells sufficient for adoptive immunotherapy.

  4. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells.

    Science.gov (United States)

    Hurton, Lenka V; Singh, Harjeet; Najjar, Amer M; Switzer, Kirsten C; Mi, Tiejuan; Maiti, Sourindra; Olivares, Simon; Rabinovich, Brian; Huls, Helen; Forget, Marie-Andrée; Datar, Vrushali; Kebriaei, Partow; Lee, Dean A; Champlin, Richard E; Cooper, Laurence J N

    2016-11-29

    Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (TSCM) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR(+) T cells with preserved TSCM potential using the Sleeping Beauty platform. Because IL-15 is fundamental to T-cell memory, we incorporated its costimulatory properties by coexpressing CAR with a membrane-bound chimeric IL-15 (mbIL15). The mbIL15-CAR T cells signaled through signal transducer and activator of transcription 5 to yield improved T-cell persistence independent of CAR signaling, without apparent autonomous growth or transformation, and achieved potent rejection of CD19(+) leukemia. Long-lived T cells were CD45RO(neg)CCR7(+)CD95(+), phenotypically most similar to TSCM, and possessed a memory-like transcriptional profile. Overall, these results demonstrate that CAR(+) T cells can develop long-term persistence with a memory stem-cell phenotype sustained by signaling through mbIL15. This observation warrants evaluation in clinical trials.

  5. Tethered IL-15 augments antitumor activity and promotes a stem-cell memory subset in tumor-specific T cells

    Science.gov (United States)

    Hurton, Lenka V.; Singh, Harjeet; Najjar, Amer M.; Switzer, Kirsten C.; Mi, Tiejuan; Maiti, Sourindra; Olivares, Simon; Rabinovich, Brian; Huls, Helen; Forget, Marie-Andrée; Datar, Vrushali; Kebriaei, Partow; Lee, Dean A.; Champlin, Richard E.; Cooper, Laurence J. N.

    2016-01-01

    Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (TSCM) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR+ T cells with preserved TSCM potential using the Sleeping Beauty platform. Because IL-15 is fundamental to T-cell memory, we incorporated its costimulatory properties by coexpressing CAR with a membrane-bound chimeric IL-15 (mbIL15). The mbIL15-CAR T cells signaled through signal transducer and activator of transcription 5 to yield improved T-cell persistence independent of CAR signaling, without apparent autonomous growth or transformation, and achieved potent rejection of CD19+ leukemia. Long-lived T cells were CD45ROnegCCR7+CD95+, phenotypically most similar to TSCM, and possessed a memory-like transcriptional profile. Overall, these results demonstrate that CAR+ T cells can develop long-term persistence with a memory stem-cell phenotype sustained by signaling through mbIL15. This observation warrants evaluation in clinical trials. PMID:27849617

  6. Study on T lymphocyte subsets and NK cells in patients with Graves disease combined with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    魏枫; 杜婧; 苏秀兰; 乌兰; 王津京; 霍晓静

    2008-01-01

    Objective To investigate changes in T lymphocyte subsets and NK cells in patients with simple Graves' disease(GD)and Graves' disease combined with type 2 diabetes mellitus(GD/T2DM).Methods Fifteen cases of GD/T2DM were selected from our hospital from November 2001 to November 2004.Before and after therapy thyroid function,thyroglobulin antibody(TGA),thyroid microsomal antibody(TMA)and blood glucose level were measured,and T lymphocyte subsets(CD3,CD4,CD8,CD4/CD8)and NK cells(CD56)were measured by immunofluo...

  7. Crosstalk between dendritic cell subsets and implications for dendritic cell-based anticancer immunotherapy

    NARCIS (Netherlands)

    Bakdash, G.; Schreurs, I.; Schreibelt, G.; Tel, J.

    2014-01-01

    Dendritic cells (DCs) are a family of professional antigen-presenting cells that have an indispensable role in the initiation of innate and adaptive immune responses against pathogens and tumor cells. The DC family is very heterogeneous. Two main types of naturally occurring DCs circulate in periphe

  8. [Expression of activating and inhibitory receptors on peripheral blood natural killer cell subsets of women with reproductive failures].

    Science.gov (United States)

    Baltadzheiva, D; Penkova, K; Stamenov, G; Dimitrova, D; Michailova, A

    2010-01-01

    It is now apparent that immunologic implantation failure and recurrent abortions are more than likely mediated through activation of natural killer (NK) cells. The NK cell activity is mediated by a balance between activating and inhibitory receptors upon recognition of MHC class I molecules. In this study, we investigated by flow cytometry the expression of activating and inhibitory receptors on NK cells of women with reproductive failures- recurrent spontaneous abortion (RSA) and implantation failures (IF). In women with implantation failures CD56+CD16+ NK cell subset was significantly increased (p = 0.017) and CD158a expressing NK cells was significantly decreased (p = 0.027). CD161-activating receptor expressing CD56+ NK cells were significantly decreased in women with RSA (p = 0.033). These data further support an imbalance in NK cell subsets in women with reproductive failures.

  9. Detection of the meq gene in the T cell subsets from chickens infected with Marek's disease virus serotype 1.

    Science.gov (United States)

    Chang, Kyung-Soo; Ohashi, Kazuhiko; Lee, Sung-Il; Takagi, Michihiro; Onum, Misao

    2005-08-01

    The meq gene was thought to be only detected in Marek's disease virus serotype 1 (MDV 1) including a very virulent strain, Md5, while L-meq, in which a 180-bp sequence is inserted into the meq open reading frame, is found in other strains of MDV 1, such as CVI 988/R6. However, both meq and L-meq were previously detected by PCR in chickens infected with MDV 1, suggesting that MDV 1 may consists of at least two subpopulations, one with meq, the other with L-meq. To further analyze these subpopulations, we analyzed the time course changes in distribution of these subpopulations among T cell subsets from chickens infected with MDV 1. Both meq and L-meq were detected in CD4+ and CD8+ T cells infected with strain Md5 or CVI 988/R6. The shift in MDV subpopulations from one displaying meq to the other displaying L-meq and/or the conversion from meq to L-meq occurred mainly in the CD8+ T cell subset from Md5-infected chickens. PCR products corresponding to L-meq rather than meq were frequently amplified from the CD8+ T cell subset from CVI 988/R 6 -infected chickens. These results suggest that a dominant subpopulation of MDV 1 changes depending on the T cell subsets, and that L-meq is dominantly present in the CD8+ T cells which play a role in the clearance of pathogenic agents.

  10. Effect of irradiation on human T-cell proliferation: low dose irradiation stimulates mitogen-induced proliferation and function of the suppressor/cytotoxic T-cell subset

    Energy Technology Data Exchange (ETDEWEB)

    Gualde, N.; Goodwin, J.S.

    1984-04-01

    Unfractionated human T cells exposed to 10-50 rad of X irradiation incorporated less (/sup 3/H)thymidine than nonirradiated T cells when subsequently cultured with PHA or Con A. The cytotoxic/suppressor T-cell subset, isolated as either OKT8(+) or OKT4(-) cells, demonstrated significantly enhanced (/sup 3/H)thymidine incorporation in PHA- or Con A-stimulated cultures after exposure to 10-50 rad, compared to unirradiated cells, while the proliferation of the OKT4(+) helper/inducer subset was inhibited by low dose irradiation. It has been previously reported that approximately 30% of the cytotoxic/suppressor subset also stains with OKM1. When the cytotoxic/suppressor subset was further subdivided into OKT4(-), OKM1(+), and OKT4(-), OKM1(-) cells, proliferation of the OKT4(-), OKM1(+) population was inhibited by exposure to 25 rad while proliferation of the OKT4(-), OKM1(-) population was stimulated. The increase in proliferation of the cytotoxic/suppressor T-cell subset after low dose irradiation is paralleled by an increase in suppressor activity of these cells. T cells exposed to 25 rad and then cultured with Con A for 48 hr caused greater inhibition of IgG production when added to fresh autologous lymphocytes stimulated by pokeweed mitogen than did unirradiated cells. Thus, low dose irradiation enhances both the proliferation and function of the human suppressor T-cell subset.

  11. Brucella discriminates between mouse dendritic cell subsets upon in vitro infection.

    Science.gov (United States)

    Papadopoulos, Alexia; Gagnaire, Aurélie; Degos, Clara; de Chastellier, Chantal; Gorvel, Jean-Pierre

    2016-01-01

    Brucella is a Gram-negative bacterium responsible for brucellosis, a worldwide re-emerging zoonosis. Brucella has been shown to infect and replicate within Granulocyte macrophage colony-stimulating factor (GMCSF) in vitro grown bone marrow-derived dendritic cells (BMDC). In this cell model, Brucella can efficiently control BMDC maturation. However, it has been shown that Brucella infection in vivo induces spleen dendritic cells (DC) migration and maturation. As DCs form a complex network composed by several subpopulations, differences observed may be due to different interactions between Brucella and DC subsets. Here, we compare Brucella interaction with several in vitro BMDC models. The present study shows that Brucella is capable of replicating in all the BMDC models tested with a high infection rate at early time points in GMCSF-IL15 DCs and Flt3l DCs. GMCSF-IL15 DCs and Flt3l DCs are more activated than the other studied DC models and consequently intracellular bacteria are not efficiently targeted to the ER replicative niche. Interestingly, GMCSF-DC and GMCSF-Flt3l DC response to infection is comparable. However, the key difference between these 2 models concerns IL10 secretion by GMCSF DCs observed at 48 h post-infection. IL10 secretion can explain the weak secretion of IL12p70 and TNFα in the GMCSF-DC model and the low level of maturation observed when compared to GMCSF-IL15 DCs and Flt3l DCs. These models provide good tools to understand how Brucella induce DC maturation in vivo and may lead to new therapeutic design using DCs as cellular vaccines capable of enhancing immune response against pathogens.

  12. Bonzo/CXCR6 expression defines type 1–polarized T-cell subsets with extralymphoid tissue homing potential

    OpenAIRE

    2001-01-01

    Chemokine receptor expression is finely controlled during T-cell development. We show that newly identified chemokine receptor Bonzo/CXCR6 is expressed by subsets of Th1 or T-cytotoxic 1 (Tc1) cells, but not by Th2 or Tc2 cells, establishing Bonzo as a differential marker of polarized type 1 T cells in vitro and in vivo. Priming of naive T cells by dendritic cells induces expression of Bonzo on T cells. IL-12 enhances this dendritic cell–dependent upregulation, while IL-4 inhibits it. In bloo...

  13. Characterization of Peripheral Immune Cell Subsets in Patients with Acute and Chronic Cerebrovascular Disease: A Case-Control Study

    Directory of Open Access Journals (Sweden)

    Peter Kraft

    2015-10-01

    Full Text Available Immune cells (IC play a crucial role in murine stroke pathophysiology. However, data are limited on the role of these cells in ischemic stroke in humans. We therefore aimed to characterize and compare peripheral IC subsets in patients with acute ischemic stroke/transient ischemic attack (AIS/TIA, chronic cerebrovascular disease (CCD and healthy volunteers (HV. We conducted a case-control study of patients with AIS/TIA (n = 116 or CCD (n = 117, and HV (n = 104 who were enrolled at the University Hospital Würzburg from 2010 to 2013. We determined the expression and quantity of IC subsets in the three study groups and performed correlation analyses with demographic and clinical parameters. The quantity of several IC subsets differed between the AIS/TIA, CCD, and HV groups. Several clinical and demographic variables independently predicted the quantity of IC subsets in patients with AIS/TIA. No significant changes in the quantity of IC subsets occurred within the first three days after AIS/TIA. Overall, these findings strengthen the evidence for a pathophysiologic role of IC in human ischemic stroke and the potential use of IC-based biomarkers for the prediction of stroke risk. A comprehensive description of IC kinetics is crucial to enable the design of targeted treatment strategies.

  14. The role of dendritic cell subsets and innate immunity in the pathogenesis of type 1 diabetes and other autoimmune diseases

    OpenAIRE

    Price, Jeffrey D; Tarbell, Kristin V.

    2015-01-01

    Dendritic cells (DCs) are key antigen presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, ...

  15. The Role of Dendritic Cell Subsets and Innate Immunity in the Pathogenesis of Type 1 Diabetes and Other Autoimmune Diseases

    OpenAIRE

    Price, Jeffrey D; Tarbell, Kristin V.

    2015-01-01

    Dendritic cells (DCs) are key antigen-presenting cells that have an important role in autoimmune pathogenesis. DCs control both steady-state T cell tolerance and activation of pathogenic responses. The balance between these two outcomes depends on several factors, including genetic susceptibility, environmental signals that stimulate varied innate responses, and which DC subset is presenting antigen. Although the specific DC phenotype can diverge depending on the tissue location and context, ...

  16. Allosuppressor- and allohelper-T cells in acute and chronic graft-vs. -host (GVH) disease. III. Different Lyt subsets of donor T cells induce different pathological syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Rolink, A.G.; Gleichmann, E.

    1983-08-01

    Previous work from this laboratory has led to the hypothesis that the stimulatory pathological symptoms of chronic graft-vs.-host disease (GVHD) are caused by alloreactive donor T helper (TH) cells, whereas the suppressive pathological symptoms of acute GVHD are caused by alloreactive T suppressor (TS) cells of the donor. We analyzed the Lyt phenotypes of B10 donor T cells required for the induction of either acute or chronic GVHD in H-2-different (B10 X DBA/2)F1 recipients. When nonirradiated F1 mice were used as the recipients, we found unseparated B10 T cells induced only a moderate formation of systemic lupus erythematosus (SLE)-like autoantibodies, but a high percentage of lethal GVHD (LGVHD). In contrast, Lyt-1+2- donor T cells were unable to induce LGVHD in these recipients but were capable of inducing a vigorous formation of SLE-like autoantibodies and severe immune-complex glomerulonephritis. Lyt-1-2+ T cells were incapable of inducing either acute or chronic GVHD. The sensitivity and accuracy of the GVH system were increased by using irradiated F1 mice as recipients and then comparing donor-cell inocula that contained similar numbers of T lymphocytes. Donor-cell inocula were used that had been tested for their allohelper and allosuppressor effects on F1 B cells in vitro. In the irradiated F1 recipients unseparated donor T cells were superior to T cell subsets in inducing LGVHD. In contrast Lyt-1+2- T cells, but neither unseparated T cells nor Lyt-1-2+ T cells, were capable of inducing a vigorous formation of SLE-like auto-antibodies. We conclude that the stimulatory pathological symptoms of chronic GVHD are caused by Lyt-1+2- allohelper T cells. In contrast, the development of the suppressive pathological symptoms of acute GVHD appears to involve alloreactive Lyt-1+2+ T suppressor cells.

  17. Different spectra of recurrent gene mutations in subsets of chronic lymphocytic leukemia harboring stereotyped B-cell receptors

    DEFF Research Database (Denmark)

    Sutton, Lesley-Ann; Young, Emma; Baliakas, Panagiotis

    2016-01-01

    We report on markedly different frequencies of genetic lesions within subsets of chronic lymphocytic leukemia patients carrying mutated or unmutated stereotyped B-cell receptor immunoglobulins in the largest cohort (n=565) studied for this purpose. By combining data on recurrent gene mutations (B...

  18. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    Science.gov (United States)

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast™ chemical screening and prioritization research project. Metabolites from hES cultur...

  19. The changes and significance of T cell subsets and cytokines in the induced sputum in children with asthma

    Institute of Scientific and Technical Information of China (English)

    Zu-Hui Tian; Feng-Qiong Zuo; Wei Zhang

    2016-01-01

    Objective:To explore the changes and significance of T cell subsets and cytokines in the induced sputum in children with asthma.Methods:A total of 86 cases of children with asthma were selected as research objects in the observation group, while a total of 35 cases of healthy children were chosen as research objects in the control group. Lung function indexes including the ratio (FEV1%) of forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) and the maximum peak expiratory flow (PEF), and inflammatory cytokines in the induced sputum including interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and T cell subsets including Th1 cells, CD8+CD28- Treg cells, CD4+CD25+ Treg cells, Th2 cells and Th17 cells, and T cell subsets related cytokines including interferon-γ (IFN-γ), transforming growth factor-β (TGF-β), interleukin-4 (IL-4), and interleukin-17A (IL-17A) were all detected and compared between the two groups.Results:The levels of IL-8, TNF-α and IL-6 in the induced sputum in the observation group were significantly higher than those in the control group (P<0.05), while FEV1% and PEF were significantly decreased in the observation group compared with the control group (P<0.05); the number of Th1 cells, CD8+CD28- Treg cells and CD4+CD25+ Treg cells in the induced sputum was significantly lower, while the number of Th2 cells and Th17 cells was significantly higher in the observation group than that in the control group (P<0.05); the expression levels of IFN-γ from Th1 cells and TGF-β from Treg cells were significantly lower, while the expression levels of IL-4 from Th2 cells and IL-17A from Th17 cells were significantly higher in the observation group than those in the control group (P<0.05).Conclusions:The number of T cell subsets in the induced sputum in children with asthma is abnormal, showing increases in the number of the Th2 cells and Th17 cells as well as their related cytokines, and decreases in the

  20. CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver.

    Science.gov (United States)

    Stegmann, Kerstin A; Robertson, Francis; Hansi, Navjyot; Gill, Upkar; Pallant, Celeste; Christophides, Theodoros; Pallett, Laura J; Peppa, Dimitra; Dunn, Claire; Fusai, Giuseppe; Male, Victoria; Davidson, Brian R; Kennedy, Patrick; Maini, Mala K

    2016-05-23

    Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p hi)Eomes(lo)(CXCR6-) and T-bet(lo)Eomes(hi)(CXCR6+); the latter was virtually absent in the periphery. The small circulating CXCR6+ subset was predominantly T-bet(hi)Eomes(lo), suggesting its lineage was closer to CXCR6- peripheral than CXCR6+ liver NK. These data reveal a large subset of human liver-resident T-bet(lo)Eomes(hi) NK, distinguished by their surface expression of CXCR6, adapted for hepatic tolerance and inducible anti-viral immunity.

  1. Specific roles for dendritic cell subsets during initiation and progression of psoriasis

    OpenAIRE

    Glitzner, Elisabeth; Korosec, Ana; Brunner, Patrick M.; Drobits, Barbara; Amberg, Nicole; Schonthaler, Helia B.; Kopp, Tamara; Wagner, Erwin F.; Stingl, Georg; Holcmann, Martin; Sibilia, Maria

    2014-01-01

    Several subtypes of APCs are found in psoriasis patients, but their involvement in disease pathogenesis is poorly understood. Here, we investigated the contribution of Langerhans cells (LCs) and plasmacytoid DCs (pDCs) in psoriasis. In human psoriatic lesions and in a psoriasis mouse model (DKO* mice), LCs are severely reduced, whereas pDCs are increased. Depletion of pDCs in DKO* mice prior to psoriasis induction resulted in a milder phenotype, whereas depletion during active disease had no ...

  2. Human NK cell subsets redistribution in pathological conditions: A role for CCR7 receptor

    Directory of Open Access Journals (Sweden)

    Silvia Pesce

    2016-10-01

    Full Text Available Innate and adaptive immunity has evolved complex molecular mechanisms regulating immune cell migration to facilitate the dynamic cellular interactions required for its function involving the chemokines and their receptors.One important chemokine receptor in the immune system is represented by CCR7. Together with its ligands CCL19 and CCL21, this chemokine receptor controls different arrays of migratory events, both in innate and adaptive immunity, including homing of CD56bright NK cells, T cells and DCs to lymphoid compartments where T cell priming occurs. Only recently, a key role for CCR7 in promoting CD56dim NK cell migration towards lymphoid tissues has been described. Remarkably, this event can influence the shaping and polarization of adaptive T cell responses.In this review, we describe recent progress in understanding the mechanisms and the site where CD56dim KIR+ NK cells can acquire the capability to migrate towards lymph nodes. The emerging significance of this event in clinical transplantation is also discussed.

  3. CD45/CD11b Positive Subsets of Adult Lung Anchorage-Independent Cells Harness Epithelial Stem Cells

    Science.gov (United States)

    Peter, Yakov; Sen, Namita; Levantini, Elena; Keller, Steven; Ingenito, Edward P; Ciner, Aaron; Sackstein, Robert; Shapiro, Steven D

    2015-01-01

    Compensatory growth is mediated by multiple cell types that interact during organ repair. To elucidate the relationship between the stem/progenitor cells that proliferate or differentiate and the somatic cells of lung, we utilized a novel ex vivo pneumoexplant system. Applying this technique, we identified a sustained culture of repopulating adult progenitors in the form of free floating anchorage-independent cells (AICs). AICs did not express integrin proteins α5, β3, and β7, and constituted 37% of the total culture at day 14, yielding a mixed yet conserved population that recapitulated RNA expression patterns of the healthy lung. AICs exhibited rapid proliferation manifested by a marked 60-fold increase in cell numbers by day 21. Over 50% of the AIC population was cKit+ or double-positive for CD45+ and CD11b+ antigenic determinants, consistent with cells of hematopoietic origin. The latter subset was found to be enriched with prosurfactant protein-C and SCGB1A1 expressing putative stem cells and with aquaporin-5 producing cells, characteristic of terminally differentiated alveolar epithelial type-1 pneumocytes. AICs undergo remodeling to form a cellular lining at the air/gel interface, and TGFβ1 treatment modifies protein expression, implying direct-differentiation of this population. These data confirm the active participation of clonogenic hematopietic stem cells in a mammalian model of lung repair and validate mixed stem/somatic cell cultures, which embrace sustained cell viability, proliferation, and differentiation, for use in studies of compensatory pulmonary growth. PMID:22585451

  4. Role of Ets Proteins in Development, Differentiation, and Function of T-Cell Subsets.

    Science.gov (United States)

    Liu, Mian; Gao, Weiwu; van Velkinburgh, Jennifer C; Wu, Yuzhang; Ni, Bing; Tian, Yi

    2016-03-01

    Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, that play distinctive roles in the immune system. Development, differentiation, and function of thymocytes and CD4(+) and CD8(+) T cells are controlled by a multitude of secreted and intracellular factors, ranging from cytokine signaling modules to transcription factors and epigenetic modifiers. Members of the E26 transformation specific (Ets) family of transcription factors, in particular, are potent regulators of these CD4(+) or CD8(+) T-cell processes. In this review, we summarize and discuss the functions and underlying mechanisms of the Ets family members that have been characterized as involved in these processes. Ongoing research of these factors is expected to identify practical applications for the Ets family members as novel therapeutic targets for inflammation-related diseases.

  5. FGFR4 signaling couples to Bim and not Bmf to discriminate subsets of alveolar rhabdomyosarcoma cells.

    Science.gov (United States)

    Wachtel, Marco; Rakic, Jelena; Okoniewski, Michal; Bode, Peter; Niggli, Felix; Schäfer, Beat W

    2014-10-01

    Biological heterogeneity represents a major obstacle for cancer treatment. Therefore, characterization of treatment-relevant tumor heterogeneity is necessary to develop more effective therapies in the future. Here, we uncovered population heterogeneity among PAX/FOXO1-positive alveolar rhabdomyosarcoma by characterizing prosurvival networks initiated by FGFR4 signaling. We found that FGFR4 signaling rescues only subgroups of alveolar rhabdomyosarcoma cells from apoptosis induced by compounds targeting the IGF1R-PI3K-mTOR pathway. Differences in both proapoptotic machinery and FGFR4-activated signaling are involved in the different behavior of the phenotypes. Proapoptotic stress induced by the kinase inhibitors is sensed by Bim/Bad in rescue cells and by Bmf in nonrescue cells. Anti-apoptotic ERK1/2 signaling downstream of FGFR4 is long-lasting in rescue and short-termed in most non-rescue cells. Gene expression analysis detected signatures specific for these two groups also in biopsy samples. The different cell phenotypes are present in different ratios in alveolar rhabdomyosarcoma tumors and can be identified by AP2β expression levels. Hence, inhibiting FGFR signaling might represent an important strategy to enhance efficacy of current RMS treatments.

  6. Early interferon-γ production in human lymphocyte subsets in response to nontyphoidal Salmonella demonstrates inherent capacity in innate cells.

    Directory of Open Access Journals (Sweden)

    Tonney S Nyirenda

    Full Text Available BACKGROUND: Nontyphoidal Salmonellae frequently cause life-threatening bacteremia in sub-Saharan Africa. Young children and HIV-infected adults are particularly susceptible. High case-fatality rates and increasing antibiotic resistance require new approaches to the management of this disease. Impaired cellular immunity caused by defects in the T helper 1 pathway lead to intracellular disease with Salmonella that can be countered by IFNγ administration. This report identifies the lymphocyte subsets that produce IFNγ early in Salmonella infection. METHODOLOGY: Intracellular cytokine staining was used to identify IFNγ production in blood lymphocyte subsets of ten healthy adults with antibodies to Salmonella (as evidence of immunity to Salmonella, in response to stimulation with live and heat-killed preparations of the D23580 invasive African isolate of Salmonella Typhimurium. The absolute number of IFNγ-producing cells in innate, innate-like and adaptive lymphocyte subpopulations was determined. PRINCIPAL FINDINGS: Early IFNγ production was found in the innate/innate-like lymphocyte subsets: γδ-T cells, NK cells and NK-like T cells. Significantly higher percentages of such cells produced IFNγ compared to adaptive αβ-T cells (Student's t test, P<0.001 and ≤0.02 for each innate subset compared, respectively, with CD4(+- and CD8(+-T cells. The absolute numbers of IFNγ-producing cells showed similar differences. The proportion of IFNγ-producing γδ-T cells, but not other lymphocytes, was significantly higher when stimulated with live compared with heat-killed bacteria (P<0.0001. CONCLUSION/SIGNIFICANCE: Our findings indicate an inherent capacity of innate/innate-like lymphocyte subsets to produce IFNγ early in the response to Salmonella infection. This may serve to control intracellular infection and reduce the threat of extracellular spread of disease with bacteremia which becomes life-threatening in the absence of protective antibody

  7. Influenza a virus induces an immediate cytotoxic activity in all major subsets of peripheral blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Sanda Sturlan

    Full Text Available BACKGROUND: A replication defective influenza A vaccine virus (delNS1 virus was developed. Its attenuation is due to potent stimulation of the innate immune system by the virus. Since the innate immune system can also target cancer cells, we reasoned that delNS1 virus induced immune-stimulation should also lead to the induction of innate cytotoxic effects towards cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood mononuclear cells (PBMCs, isolated CD56+, CD3+, CD14+ and CD19+ subsets and different combinations of the above subsets were stimulated by delNS1, wild type (wt virus or heat inactivated virus and co-cultured with tumor cell lines in the presence or absence of antibodies against the interferon system. Stimulation of PBMCs by the delNS1 virus effectively induced cytotoxicity against different cancer cell lines. Surprisingly, virus induced cytotoxicity was exerted by all major subtypes of PBMCs including CD56+, CD3+, CD14+ and CD19+ cells. Virus induced cytotoxicity in CD3+, CD14+ and CD19+ cells was dependent on virus replication, whereas virus induced cytotoxicity in CD56+ cells was only dependent on the binding of the virus. Virus induced cytotoxicity of isolated cell cultures of CD14+, CD19+ or CD56+ cells could be partially blocked by antibodies against type I and type II (IFN interferon. In contrast, virus induced cytotoxicity in the complete PBMC preparation could not be inhibited by blocking type I or type II IFN, indicating a redundant system of activation in whole blood. CONCLUSIONS/SIGNIFICANCE: Our data suggest that apart from their well known specialized functions all main subsets of peripheral blood cells also initially exert a cytotoxic effect upon virus stimulation. This closely links the innate immune system to the adaptive immune response and renders delNS1 virus a potential therapeutic tool for viro-immunotherapy of cancer.

  8. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane

    DEFF Research Database (Denmark)

    Rørvig, Sara; Østergaard, Ole; Heegaard, Niels Henrik Helweg;

    2013-01-01

    granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four-layer Percoll gradient. Granule subsets were pooled and subjected to SDS-PAGE, and gel pieces were in...

  9. Histological lesions, cell cycle arrest, apoptosis and T cell subsets changes of spleen in chicken fed aflatoxin-contaminated corn.

    Science.gov (United States)

    Peng, Xi; Zhang, Keying; Bai, Shiping; Ding, Xuemei; Zeng, Qiufeng; Yang, Jun; Fang, Jing; Chen, Kejie

    2014-08-20

    The purpose of this study was to evaluate the effects of corn naturally contaminated with aflatoxin B1 and aflatoxin B2 on pathological lesions, apoptosis, cell cycle phases and T lymphocyte subsets of spleen, and to provide an experimental basis for understanding the mechanism of aflatoxin-induced immunosuppression. A total of 900 COBB500 male broilers were randomly allocated into five groups with six replicates per group and 30 birds per replicate. The experiment lasted for 6 weeks and the five dietary treatments consisted of control, 25% contaminated corn, 50% contaminated corn, 75% contaminated corn and 100% contaminated corn groups. The histopathological spleen lesions from the contaminated corn groups was characterized as congestion of red pulp, increased necrotic cells and vacuoles in the splenic corpuscle and periarterial lymphatic sheath. The contaminated corn intake significantly increased relative weight of spleen, percentages of apoptotic splenocytes, induced cell cycle arrest of splenocytes, increased the percentages of CD3+CD8+ T cells and decreased the ratios of CD3+CD4+ to CD3+CD8+. The results suggest that AFB-induced immunosuppression maybe closely related to the lesions of spleen.

  10. Antigen-specific regulatory T-cell subsets in transplantation tolerance regulatory T-cell subset quality reduces the need for quantity.

    NARCIS (Netherlands)

    Koenen, H.J.P.M.; Joosten, I.

    2006-01-01

    Regulatory T cells (Treg) are critical controllers of the immune response. Disturbed Treg function results in autoimmunity, whereas in transplantation Treg are crucial in graft survival and transplant tolerance. Hence therapeutic modalities that influence Treg numbers or function hold great clinical

  11. Data on correlations between T cell subset frequencies and length of partial remission in type 1 diabetes.

    Science.gov (United States)

    Narsale, Aditi; Moya, Rosita; Robertson, Hannah Kathryn; Davies, Joanna Davida

    2016-09-01

    Partial remission in patients newly diagnosed with type 1 diabetes is a period of good glucose control that can last from several weeks to over a year. The clinical significance of the remission period is that patients might be more responsive to immunotherapy if treated within this period. This article provides clinical data that indicates the level of glucose control and insulin-secreting β-cell function of each patient in the study at baseline (within 3 months of diagnosis), and at 3, 6, 9, 12, 18 and 24 months post-baseline. The relative frequency of immune cell subsets in the PBMC of each patient and the association between the frequency of immune cell subsets measured and length of remission is also shown. These data support the findings reported in the accompanying publication, "A pilot study showing associations between frequency of CD4+ memory cell subsets at diagnosis and duration of partial remission in type 1 diabetes" (Moya et al., 2016) [1], where a full interpretation, including biological relevance of the study can be found.

  12. Interplay among cytokines and T cell subsets in the progression and control of immune-mediated diseases.

    Science.gov (United States)

    Moudgil, Kamal D

    2015-07-01

    Cytokines serve as key mediators of inflammation and tissue damage in a variety of immune-mediated disorders. The induction, progression, and resolution of inflammation in such disorders are characterized by a dynamic balance between both the pro-inflammatory and anti-inflammatory cytokines as well as the pathogenic and protective T cell subsets. Over the past two decades, the roles of the interleukin-17 (IL-17) /IL-23 axis and the T helper 17 (Th17)/ T regulatory (Treg) cell balance in the pathogenesis of autoimmunity and other inflammatory diseases have extensively been analyzed, and their significance validated. However, these studies, coupled with others devoted to well-established Th1/Th2 cytokines, have unraveled some challenging issues including the dual action of cytokines and the plasticity of T cell subsets. Nevertheless, major positive advances have also been made regarding cytokines and T cell subsets as therapeutic targets/agents. In this special issue, "Cytokines in Immune Pathology and Therapy," leading experts have shared their research work and perspectives on the roles of cytokines in the development and control of immune-mediated diseases. An outline of 14 articles in the first volume is presented here. The second volume will follow soon.

  13. Glucocorticoid induced TNFR-related protein (GITR as marker of human regulatory T cells: expansion of the GITR+CD25- cell subset in patients with systemic lupus erythematosus

    Directory of Open Access Journals (Sweden)

    E. Bartoloni Bocci

    2011-06-01

    Full Text Available Objectives: Regulatory T cells (TREG represent a T cell subset able to modulate immune response by suppressing autoreactive T-lymphocytes. The evidence of a reduced number and an impaired function of this cell population in autoimmune/ inflammatory chronic diseases led to the hypothesis of its involvement in the pathogenesis of these disorders. Glucocorticoid-induced TNFR-related protein (GITR is a well known marker of murine TREG cells, but little is known in humans. The aim of this study was to investigate the characteristics of TREG cells in systemic lupus erythematosus (SLE and the potential role of GITR as marker of human TREG. Methods: Nineteen SLE patients and 15 sex- and age-matched normal controls (NC were enrolled. CD4+ T cells were magnetic sorted from peripheral blood by negative selection. Cell phenotype was analyzed through flow-cytometry using primary and secondary antibodies and real time polymerase-chain reaction (PCR using TaqMan probes. Results: The CD25highGITRhigh subset was significantly decreased in SLE patients with respect to NC (0.37±0.21% vs 0.72±0.19%; p<0.05. On the opposite, the CD25-GITRhigh cell population was expanded in the peripheral blood of SLE patients (3.5±2.25 vs 0.70±0.32%, p<0.01. Interestingly, FoxP3 at mRNA level was expressed in both CD25- GITRhigh and CD25highGITRhigh cells, suggesting that both cell subsets have regulatory activity. Conclusions: CD4+CD25-GITRhigh cells are increased in SLE as compared to NC. The expression of high level of GITR, but not CD25, on FoxP3+ cells appears to point to a regulatory phenotype of this peculiar T cell subset.

  14. T-Cell Activation induces Dynamic Changes in miRNA Expression Patterns in CD4 and CD8 T-Cell Subsets

    NARCIS (Netherlands)

    Teteloshvili, Nato; Smigielska-Czepiel, Katarzyna; Kroesen, Bart-Jan; Brouwer, Elisabeth; Kluiver, Joost; van den Berg, Anke; Boots, Anna

    2015-01-01

    T-cell activation affects microRNA (miRNA) expression in T-cell subsets. However, little is known about the kinetics of miRNA regulation and possible differences between CD4 and CD8 T cells. In this study we set out to analyze the kinetics of activation-induced expression regulation of twelve pre-se

  15. Treg/Th17 polarization by distinct subsets of breast cancer cells is dictated by the interaction with mesenchymal stem cells

    OpenAIRE

    Patel, Shyam A.; Dave, Meneka A.; Bliss, Sarah A.; Giec-Ujda, Agata B.; Bryan, Margarette; Pliner, Lillian F.; Rameshwar, Pranela

    2014-01-01

    Breast cancer (BC) cells (BCCs) exist within a hierarchy beginning with cancer stem cells (CSCs). Unsorted BCCs interact with mesenchymal stem cells (MSCs) to induce regulatory T cells (Tregs). This study investigated how distinct BCC subsets interacted with MSCs to polarize T-cell response, Tregs versus T helper 17 (Th17). This study tested BC initiating cells (CSCs) and the relatively more mature early and late BC progenitors. CSCs interacted with the highest avidity to MSCs. This interacti...

  16. Bonzo/CXCR6 expression defines type 1–polarized T-cell subsets with extralymphoid tissue homing potential

    Science.gov (United States)

    Kim, Chang H.; Kunkel, Eric J.; Boisvert, Judie; Johnston, Brent; Campbell, James J.; Genovese, Mark C.; Greenberg, Harry B.; Butcher, Eugene C.

    2001-01-01

    Chemokine receptor expression is finely controlled during T-cell development. We show that newly identified chemokine receptor Bonzo/CXCR6 is expressed by subsets of Th1 or T-cytotoxic 1 (Tc1) cells, but not by Th2 or Tc2 cells, establishing Bonzo as a differential marker of polarized type 1 T cells in vitro and in vivo. Priming of naive T cells by dendritic cells induces expression of Bonzo on T cells. IL-12 enhances this dendritic cell–dependent upregulation, while IL-4 inhibits it. In blood, 35–56% of Bonzo+ CD4 T cells are Th1 cells, and 60–65% of Bonzo+ CD8 T cells are Tc1 cells, while few Bonzo+ cells are type 2 T cells. Almost all Bonzo+ Tc1 cells contain preformed granzyme A and display cytotoxic effector phenotype. Most Bonzo+ T cells lack L-selectin and/or CCR7, homing receptors for lymphoid tissues. Instead, Bonzo+ T cells are dramatically enriched among T cells in tissue sites of inflammation, such as rheumatoid joints and inflamed livers. Bonzo may be important in trafficking of effector T cells that mediate type 1 inflammation, making it a potential target for therapeutic modulation of inflammatory diseases. PMID:11238560

  17. CLEC12A-Mediated Antigen Uptake and Cross-Presentation by Human Dendritic Cell Subsets Efficiently Boost Tumor-Reactive T Cell Responses.

    Science.gov (United States)

    Hutten, Tim J A; Thordardottir, Soley; Fredrix, Hanny; Janssen, Lisanne; Woestenenk, Rob; Tel, Jurjen; Joosten, Ben; Cambi, Alessandra; Heemskerk, Mirjam H M; Franssen, Gerben M; Boerman, Otto C; Bakker, Lex B H; Jansen, Joop H; Schaap, Nicolaas; Dolstra, Harry; Hobo, Willemijn

    2016-10-01

    Potent immunotherapies are urgently needed to boost antitumor immunity and control disease in cancer patients. As dendritic cells (DCs) are the most powerful APCs, they are an attractive means to reinvigorate T cell responses. An appealing strategy to use the effective Ag processing and presentation machinery, T cell stimulation and cross-talk capacity of natural DC subsets is in vivo tumor Ag delivery. In this context, endocytic C-type lectin receptors are attractive targeting molecules. In this study, we investigated whether CLEC12A efficiently delivers tumor Ags into human DC subsets, facilitating effective induction of CD4(+) and CD8(+) T cell responses. We confirmed that CLEC12A is selectively expressed by myeloid cells, including the myeloid DC subset (mDCs) and the plasmacytoid DC subset (pDCs). Moreover, we demonstrated that these DC subsets efficiently internalize CLEC12A, whereupon it quickly translocates to the early endosomes and subsequently routes to the lysosomes. Notably, CLEC12A Ab targeting did not negatively affect DC maturation or function. Furthermore, CLEC12A-mediated delivery of keyhole limpet hemocyanin resulted in enhanced proliferation and cytokine secretion by keyhole limpet hemocyanin-experienced CD4(+) T cells. Most importantly, CLEC12A-targeted delivery of HA-1 long peptide resulted in efficient Ag cross-presentation by mDCs and pDCs, leading to strong ex vivo activation of HA-1-specific CD8(+) T cells of patients after allogeneic stem cell transplantation. Collectively, these data indicate that CLEC12A is an effective new candidate with great potential for in vivo Ag delivery into mDCs and pDCs, thereby using the specialized functions and cross-talk capacity of these DC subsets to boost tumor-reactive T cell immunity in cancer patients.

  18. IFN-γ differentially regulates subsets of Gr-1(+)CD11b(+) myeloid cells in chronic inflammation.

    Science.gov (United States)

    Zhan, Xiaoxia; Fang, Yimin; Hu, Shengfeng; Wu, Yongjian; Yang, Kun; Liao, Chunxin; Zhang, Yuanqing; Huang, Xi; Wu, Minhao

    2015-08-01

    During chronic inflammation, prolonged over-reactive immune response may lead to tissue destruction, while immune suppression hinders tissue repair and pathogen elimination. Therefore, precise regulation of the immune response is needed to avoid immuno-pathology. Interferon-gamma (IFN-γ) is widely used in clinical treatment of inflammatory diseases. However, the underlying mechanism remains unclear. Here, we evaluated the role of IFN-γ on CD11b(+)Gr-1(+) myeloid cell differentiation and function, using a heat-killed Mycobacterium bovis BCG-induced chronic inflammation model. After challenge with heat-killed BCG, two subpopulations of CD11b(+)Gr-1(+) myeloid cells were generated in the mouse spleen. Phenotypical, morphological and functional analysis indicated that the CD11b(+)Gr-1(high) Ly6G(high) Ly6C(low) subset was neutrophil-like myeloid-derived inducer cells (N-MDICs), which promoted T cell activation, while the other subset was CD11b(+)Gr-1(low) Ly6G(neg) Ly6C(high) monocyte-like myeloid-derived suppressor cells (M-MDSCs) that displayed extensive suppressor function. IFN-γ treatment dampened N-MDICs-mediated T cell activation through up-regulating T cell suppressive mediators, reactive oxygen species (ROS) and arginase I. While for M-MDSCs, IFN-γ reduced their suppressing activity by decreasing the arginase activity. Our study provides evidence that IFN-γ balances the over-reactive vs compromised immune response through different regulation of distinct myeloid subsets, and therefore displays significant therapeutic potential for effective immuno-therapy of chronic inflammatory diseases.

  19. miRNA profiling of B-cell subsets: specific miRNA profile for germinal center B cells with variation between centroblasts and centrocytes.

    Science.gov (United States)

    Tan, Lu Ping; Wang, Miao; Robertus, Jan-Lukas; Schakel, Rikst Nynke; Gibcus, Johan H; Diepstra, Arjan; Harms, Geert; Peh, Suat-Cheng; Reijmers, Rogier M; Pals, Steven T; Kroesen, Bart-Jan; Kluin, Philip M; Poppema, Sibrand; van den Berg, Anke

    2009-06-01

    MicroRNAs (miRNAs) are an important class of small RNAs that regulate gene expression at the post-transcriptional level. It has become evident that miRNAs are involved in hematopoiesis, and that deregulation of miRNAs may give rise to hematopoietic malignancies. The aim of our study was to establish miRNA profiles of naïve, germinal center (GC) and memory B cells, and validate their expression patterns in normal lymphoid tissues. Quantitative (q) RT-PCR profiling revealed that several miRNAs were elevated in GC B cells, including miR-17-5p, miR-106a and miR-181b. One of the most abundant miRNAs in all three B-cell subsets analyzed was miR-150, with a more than 10-fold lower level in GC B cell as compared with the other two subsets. miRNA in situ hybridization (ISH) in tonsil tissue sections confirmed the findings from the profiling work. Interestingly, gradual decrease of miR-17-5p, miR-106a and miR-181b staining intensity from the dark to the light zone was observed in GC. A strong cytoplasmic staining of miR-150 was observed in a minority of the centroblasts in the dark zone of the GC. Inverse staining pattern of miR-150 against c-Myb and Survivin was observed in tonsil tissue sections, suggesting possible targeting of these genes by miR-150. In line with this, the experimental induction of miR-150 lead to reduced c-Myb, Survivin and Foxp1 expression levels in the Burkitt's lymphoma cell line, DG75. In conclusion, miRNA profiles of naïve, GC and memory B cells were established and validated by miRNA ISH. Within the GC cells, a marked difference was observed between the light and the dark zone.

  20. Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.

    Science.gov (United States)

    Hauswirth, Alexander W; Almeida, Julia; Nieto, Wendy G; Teodosio, Cristina; Rodriguez-Caballero, Arancha; Romero, Alfonso; López, Antonio; Fernandez-Navarro, Paulino; Vega, Tomas; Perez-Andres, Martin; Valent, Peter; Jäger, Ulrich; Orfao, Alberto

    2012-07-01

    Monoclonal B-cell lymphocytosis (MBL) with normal lymphocyte counts is associated with decreased numbers of normal circulating B-cell subsets.Little is known about the distribution of normal lymphoid cells and their subsets in the peripheral blood (PB) of subjects with monoclonal B-cell lymphocytosis (MBL). In our study, we compared the absolute number of PB lymphoid cells and their subpopulations in 95 MBL cases with normal lymphocyte counts vs. 617 age-/sex-matched non-MBL healthy subjects (controls), using highly sensitive flow cytometry. MBL cases showed significantly reduced numbers of normal circulating B-cells, at the expense of immature and naive B-cells; in addition, CD4+CD8+ double-positive T-cells and CD8+ T-cells were significantly lower and higher vs. controls, respectively. Moreover, most normal B-cell subsets were significantly decreased in PB at >1% MBL-counts, vs. "low-count" MBL cases, and lower amounts of immature/naive B-cells were detected in biclonal (particularly in cases with coexisting CLL-like- and non-CLL-like B-cell clones) vs. monoclonal MBL subjects. In summary, our results show imbalanced (reduced) absolute numbers of recently produced normal circulating B-cells (e.g., immature and naıve B-cells) in MBL, which becomes more pronounced as the MBL cell count increases.

  1. Identification of swine influenza virus epitopes and analysis of multiple specificities expressed by cytotoxic T cell subsets

    DEFF Research Database (Denmark)

    Pedersen, Lasse Eggers; Breum, Solvej Østergaard; Riber, Ulla;

    2014-01-01

    to elimination of viruses such as swine influenza virus (SwIV). This study describes the identification of SLA-presented peptide epitopes that are targets for a swine CTL response, and further analyses multiple specificities expressed by SwIV activated CTL subsets. Findings: Four SwIV derived peptides were...... identified as T cell epitopes using fluorescent influenza: SLA tetramers. In addition, multiple CTL specificities were analyzed using peptide sequence substitutions in two of the four epitope candidates analyzed. Interestingly both conserved and substituted peptides were found to stain the CD4-CD8+ T cell...

  2. Altered distribution of natural killer cell subsets identified by CD56, CD27 and CD70 in primary and chronic human immunodeficiency virus-1 infection

    Science.gov (United States)

    Titanji, Kehmia; Sammicheli, Stefano; De Milito, Angelo; Mantegani, Paola; Fortis, Claudio; Berg, Louise; Kärre, Klas; Travi, Giovanna; Tassandin, Chiara; Lopalco, Lucia; Rethi, Bence; Tambussi, Giuseppe; Chiodi, Francesca

    2008-01-01

    Human natural killer (NK) (CD3− CD56+) cells can be divided into two functionally distinct subsets, CD3− CD56dim and CD3− CD56bright. We analysed the distribution of NK cell subsets in primary and chronic human immunodeficiency virus-1 (HIV-1) infection, to determine if HIV infection stage may influence the subset distribution. In primary infection, contrary to chronic infection, the CD3− CD56dim subset was expanded compared to healthy controls. We also studied the effect of antiretroviral therapy administered early in infection and found that NK cell subset distribution was partially restored after 6 months of antiretroviral therapy in primary infection, but not normalized. Recently, NK cells have been divided into CD27− and CD27+ subsets with different migratory and functional capacity and CD27-mediated NK cell activation has been described in mice. We therefore investigated whether CD27 and/or CD70 (CD27 ligand) expression on NK cells, and thus the distribution of these novel NK subsets, was altered in HIV-1-infected patients. We found up-regulated expression of both CD27 and CD70 on NK cells of patients, resulting in higher proportions of CD27high and CD70high NK cells, and this phenomenon was more pronounced in chronic infection. Experiments conducted in vitro suggest that the high interleukin-7 levels found during HIV-1 infection may participate in up-regulation of CD70 on NK cell subsets. Imbalance of NK cell subsets and up-regulated expression of CD27 and CD70 initiated early in HIV-1 infection may indicate NK cell activation and intrinsic defects initiated by HIV-1 to disarm the innate immune response to the virus. PMID:17627773

  3. Identification of dendritic cells, B cell and T cell subsets in Tasmanian devil lymphoid tissue; evidence for poor immune cell infiltration into devil facial tumors.

    Science.gov (United States)

    Howson, Lauren J; Morris, Katrina M; Kobayashi, Takumi; Tovar, Cesar; Kreiss, Alexandre; Papenfuss, Anthony T; Corcoran, Lynn; Belov, Katherine; Woods, Gregory M

    2014-05-01

    The Tasmanian devil is under threat of extinction due to the transmissible devil facial tumor disease (DFTD). This fatal tumor is an allograft that does not induce an immune response, raising questions about the activity of Tasmanian devil immune cells. T and B cell analysis has been limited by a lack of antibodies, hence the need to produce such reagents. Amino acid sequence analysis revealed that CD4, CD8, IgM, and IgG were closely related to other marsupials. Monoclonal antibodies were produced against CD4, CD8, IgM, and IgG by generating bacterial fusion proteins. These, and commercial antibodies against CD1a and CD83, identified T cells, B cells and dendritic cells by immunohistochemistry. CD4(+) and CD8(+) T cells were identified in pouch young thymus, adult lymph nodes, spleen, bronchus- and gut-associated lymphoid tissue. Their anatomical distribution was characteristic of mammalian lymphoid tissues with more CD4(+) than CD8(+) cells in lymph nodes and splenic white pulp. IgM(+) and IgG(+) B cells were identified in adult lymph nodes, spleen, bronchus-associated lymphoid tissue and gut-associated lymphoid tissue, with more IgM(+) than IgG(+) cells. Dendritic cells were identified in lymph node, spleen and skin. This distribution is consistent with eutherian mammals and other marsupials, indicating they have the immune cell subsets for an anti-tumor immunity. Devil facial tumor disease tumors contained more CD8(+) than CD4(+) cells, but in low numbers. There were also low numbers of CD1a(+) and MHC class II(+) cells, but no CD83(+) IgM(+) or IgG(+) B cells, consistent with poor immune cell infiltration.

  4. Distribution of natural killer cells and T-lymphocyte subsets in peripheral blood, gallbladder cancer and surrounding tissue

    Institute of Scientific and Technical Information of China (English)

    Gang Liu; Hong Ren; Xue-Jun Sun; Jing-Sen Shi

    2007-01-01

    BACKGROUND:The patient with malignant tumor always show immunologic function drawback and ingravescent with tumor development, especially in the aspect of cell-mediated immunity. This study was undertaken to deifne the relationship between the immune function of local cells and cancer development by investigating the distribution of natural killer (NK) cells and T-lymphocyte subsets in peripheral blood, the cancer tissue and the tissue surrounding gallbladder carcinoma. METHODS:The numbers of CD4+and CD8+T-lymphocytes and NK cells were measured by lfow cytometry in samples taken from gallbladder cancer tissue, the surrounding tissues and peripheral blood of 38 patients, and compared with the numbers in the peripheral blood and gallbladder tissue of 30 patients with cholecystitis as controls. RESULTS:The numbers of CD4+and CD8+T-cells and NK cells in gallbladder cancer tissues were signiifcantly higher than those in the surrounding tissue and gallbladder with gallstone. However, the ratio of CD4+/CD8+was lower in the cancer tissue than that in the surrounding tissue and tissue from gallbladders with gallstones. The distribution of CD4+ and CD8+ T-cells and NK cells in mucous membrane of cholecystitis gallbladder and that in the tissue surrounding gallbladder cancer were signiifcantly different. CONCLUSIONS:Disproportionate and imbalanced distri-bution of NK cells and subsets of T-lymphocytes occurs in the mucous membrane proper of gallbladder cancer and surrounding tissue. Although gallbladder cancer tissue has higher expressions of CD4+, CD8+and NK cells, the immune function is low or in an inhibited state. In gallbladder cancer immunization therapy, local cellular immunological function should be enhanced and the protective barrier improved.

  5. Cytokeratin 15 marks basal epithelia in developing ureters and is upregulated in a subset of urothelial cell carcinomas.

    Directory of Open Access Journals (Sweden)

    Guangping Tai

    Full Text Available The mammalian ureter contains a water-tight epithelium surrounded by smooth muscle. Key molecules have been defined which regulate ureteric bud initiation and drive the differentiation of ureteric mesenchyme into peristaltic smooth muscle. Less is known about mechanisms underlying the developmental patterning of the multilayered epithelium characterising the mature ureter. In skin, which also contains a multilayered epithelium, cytokeratin 15 (CK15, an acidic intermediate filament protein, marks cells whose progeny contribute to epidermal regeneration following wounding. Moreover, CK15+ precursor cells in skin can give rise to basal cell carcinomas. In the current study, using transcriptome microarrays of embryonic wild type mouse ureters, Krt15, coding for CK15, was detected. Quantitative polymerase chain reaction analyses confirmed the initial finding and demonstrated that Krt15 levels increased during the fetal period when the ureteric epithelium becomes multilayered. CK15 protein was undetectable in the ureteric bud, the rudiment from which the ureter grows. Nevertheless, later in fetal development, CK15 was immunodetected in a subset of basal urothelial cells in the ureteric stalk. Superficial epithelial cells, including those positive for the differentiation marker uroplakin III, were CK15-. Transformation-related protein 63 (P63 has been implicated in epithelial differentiation in murine fetal urinary bladders. In wild type fetal ureters, CK15+ cells were positive for P63, and p63 homozygous null mutant ureters lacked CK15+ cells. In these mutant ureters, sections of the urothelium were monolayered versus the uniform multilayering found in wild type littermates. Human urothelial cell carcinomas account for considerable morbidity and mortality. CK15 was upregulated in a subset of invasive ureteric and urinary bladder cancers. Thus, in ureter development, the absence of CK15 is associated with a structurally simplified urothelium whereas

  6. Monocyte Subsets Coregulate Inflammatory Responses by Integrated Signaling through TNF and IL-6 at the Endothelial Cell Interface

    Science.gov (United States)

    Chimen, Myriam; Yates, Clara M.; McGettrick, Helen M.; Ward, Lewis S. C.; Harrison, Matthew J.; Apta, Bonita; Dib, Lea H.; Imhof, Beat A.; Harrison, Paul; Nash, Gerard B.

    2017-01-01

    Two major monocyte subsets, CD14+CD16− (classical) and CD14+/dimCD16+ (nonclassical/intermediate), have been described. Each has different functions ascribed in its interactions with vascular endothelial cells (EC), including migration and promoting inflammation. Although monocyte subpopulations have been studied in isolated systems, their influence on EC and on the course of inflammation has been ignored. In this study, using unstimulated or cytokine-activated EC, we observed significant differences in the recruitment, migration, and reverse migration of human monocyte subsets. Associated with this, and based on their patterns of cytokine secretion, there was a difference in their capacity to activate EC and support the secondary recruitment of flowing neutrophils. High levels of TNF were detected in cocultures with nonclassical/intermediate monocytes, the blockade of which significantly reduced neutrophil recruitment. In contrast, classical monocytes secreted high levels of IL-6, the blockade of which resulted in increased neutrophil recruitment. When cocultures contained both monocyte subsets, or when conditioned supernatant from classical monocytes cocultures (IL-6hi) was added to nonclassical/intermediate monocyte cocultures (TNFhi), the activating effects of TNF were dramatically reduced, implying that when present, the anti-inflammatory activities of IL-6 were dominant over the proinflammatory activities of TNF. These changes in neutrophil recruitment could be explained by regulation of E-selectin on the cocultured EC. This study suggests that recruited human monocyte subsets trigger a regulatory pathway of cytokine-mediated signaling at the EC interface, and we propose that this is a mechanism for limiting the phlogistic activity of newly recruited monocytes. PMID:28193827

  7. Insight into the immunobiology of human skin and functional specialization of skin dendritic cell subsets to innovate intradermal vaccination design.

    Science.gov (United States)

    Teunissen, M B M; Haniffa, M; Collin, M P

    2012-01-01

    Dendritic cells (DC) are the key initiators and regulators of any immune response which determine the outcome of CD4(+) and CD8(+) T-cell responses. Multiple distinct DC subsets can be distinguished by location, phenotype, and function in the homeostatic and inflamed human skin. The function of steady-state cutaneous DCs or recruited inflammatory DCs is influenced by the surrounding cellular and extracellular skin microenvironment. The skin is an attractive site for vaccination given the extended local network of DCs and the easy access to the skin-draining lymph nodes to generate effector T cells and immunoglobulin-producing B cells for long-term protective immunity. In the context of intradermal vaccination we describe in this review the skin-associated immune system, the characteristics of the different skin DC subsets, the mechanism of antigen uptake and presentation, and how the properties of DCs can be manipulated. This knowledge is critical for the development of intradermal vaccine strategies and supports the concept of intradermal vaccination as a superior route to the conventional intramuscular or subcutaneous methods.

  8. Differential Gene Expression in Thrombomodulin (TM; CD141)+ and TM− Dendritic Cell Subsets

    OpenAIRE

    Masaaki Toda; Zhifei Shao; Yamaguchi, Ken D.; Takehiro Takagi; Corina N D'Alessandro-Gabazza; Osamu Taguchi; Hugh Salamon; Leung, Lawrence L. K.; Gabazza, Esteban C.; John Morser

    2013-01-01

    Previously we have shown in a mouse model of bronchial asthma that thrombomodulin can convert immunogenic conventional dendritic cells into tolerogenic dendritic cells while inducing its own expression on their cell surface. Thrombomodulin(+) dendritic cells are tolerogenic while thrombomodulin(-) dendritic cells are pro-inflammatory and immunogenic. Here we hypothesized that thrombomodulin treatment of dendritic cells would modulate inflammatory gene expression. Murine bone marrow-derived de...

  9. Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.

    Science.gov (United States)

    Banchereau, Romain; Baldwin, Nicole; Cepika, Alma-Martina; Athale, Shruti; Xue, Yaming; Yu, Chun I; Metang, Patrick; Cheruku, Abhilasha; Berthier, Isabelle; Gayet, Ingrid; Wang, Yuanyuan; Ohouo, Marina; Snipes, LuAnn; Xu, Hui; Obermoser, Gerlinde; Blankenship, Derek; Oh, Sangkon; Ramilo, Octavio; Chaussabel, Damien; Banchereau, Jacques; Palucka, Karolina; Pascual, Virginia

    2014-10-22

    The mechanisms by which microbial vaccines interact with human APCs remain elusive. Herein, we describe the transcriptional programs induced in human DCs by pathogens, innate receptor ligands and vaccines. Exposure of DCs to influenza, Salmonella enterica and Staphylococcus aureus allows us to build a modular framework containing 204 transcript clusters. We use this framework to characterize the responses of human monocytes, monocyte-derived DCs and blood DC subsets to 13 vaccines. Different vaccines induce distinct transcriptional programs based on pathogen type, adjuvant formulation and APC targeted. Fluzone, Pneumovax and Gardasil, respectively, activate monocyte-derived DCs, monocytes and CD1c+ blood DCs, highlighting APC specialization in response to vaccines. Finally, the blood signatures from individuals vaccinated with Fluzone or infected with influenza reveal a signature of adaptive immunity activation following vaccination and symptomatic infections, but not asymptomatic infections. These data, offered with a web interface, may guide the development of improved vaccines.

  10. Silenced B-Cell Receptor Response To Autoantigen In A Poor-Prognostic Subset Of Chronic Lymphocytic Leukemia

    DEFF Research Database (Denmark)

    Bergh, Ann-Charlotte; Evaldsson, Chamilly; Pedersen, Lone Bredo

    2014-01-01

    receptor-signal transduction events, since it is more faithful to B-cell physiology than anti-IgM. Multivalent oxidized low-density lipoprotein showed specific binding to subset #1 IgM/IgD B-cell receptors, whereas native low-density lipoprotein did not. The antigen binding induced prompt receptor...... clustering followed by internalization. However, the receptor-signal transduction was silenced, revealing no Ca(2+) mobilization or cell-cycle entry, while phosphorylated extracellular-regulated kinase 1/2 basal levels were high and could not be elevated further by oxidized low-density lipoprotein......Chronic lymphocytic leukemia B cells express auto/xeno antigen-reactive antibodies that bind to self-epitopes and resemble natural IgM antibodies in their repertoire. One of the antigenic structures recognized is oxidation-induced malonedialdehyde that is present on low-density lipoprotein...

  11. T cell subset distribution in HIV-1 infected patients after 12 years of treatment induced viraemic suppression

    DEFF Research Database (Denmark)

    Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L;

    2012-01-01

    OBJECTIVE:: Residual immune activation and skewed T cell maturation may contribute to excess comorbidity and mortality in successfully treated HIV infected patients and long term effects of combination antiretroviral therapy (cART) on immune reconstitution remain a debated issue. We investigated...... quantitative T cell reconstitution and activation and its association to residual viraemia in patients with 12 years of viraemic suppression. DESIGN:: Blood samples collected cross-sectionally from 71 HIV infected patients with cART induced viraemic suppression through 12 years were compared to samples from 16...... healthy controls. METHODS:: Several different subsets of naïve, memory and activated T cells were analyzed in fresh whole blood by 6-color flowcytometry and ultra sensitive quantification of HIV RNA was performed. RESULTS:: HIV-infected patients (HIV+) had lower absolute and relative CD4 T cell counts...

  12. Combination of CD34-positive cell subsets with infarcted myocardium-like matrix stiffness: a potential solution to cell-based cardiac repair.

    Science.gov (United States)

    Zhang, Shuning; Ma, Xin; Yao, Kang; Zhu, Hong; Huang, Zheyong; Shen, Li; Qian, Juying; Zou, Yunzeng; Sun, Aijun; Ge, Junbo

    2014-06-01

    Detection of the optimal cell transplantation strategy for myocardial infarction (MI) has attracted a great deal of attention. Commitment of engrafted cells to angiogenesis within damaged myocardium is regarded as one of the major targets in cell-based cardiac repair. Bone marrow-derived CD34-positive cells, a well-characterized population of stem cells, might represent highly functional endothelial progenitor cells and result in the formation of new blood vessels. Recently, physical microenvironment (extracellular matrix stiffness) around the engrafted cells was found to exert an essential impact on their fate. Stem cells are able to feel and respond to the tissue-like matrix stiffness to commit to a relevant lineage. Notably, the infarct area after MI experiences a time-dependent stiffness change from flexible to rigid. Our previous observations demonstrated myocardial stiffness-dependent differentiation of the unselected bone marrow-derived mononuclear cells (BMMNCs) along endothelial lineage cells. Myocardial stiffness (~42 kPa) within the optimal time domain of cell engraftment (at week 1 to 2) after MI provided a more favourable physical microenvironment for cell specification and cell-based cardiac repair. However, the difference in tissue stiffness-dependent cell differentiation between the specific cell subsets expressing and no expressing CD34 phenotype remains uncertain. We presumed that CD34-positive cell subsets facilitated angiogenesis and subsequently resulted in cardiac repair under induction of infarcted myocardium-like matrix stiffness compared with CD34-negative cells. If the hypothesis were true, it would contribute greatly to detect the optimal cell subsets for cell therapy and to establish an optimized therapy strategy for cell-based cardiac repair.

  13. Distinct dendritic cell subsets dictate the fate decision between effector and memory CD8(+) T cell differentiation by a CD24-dependent mechanism.

    Science.gov (United States)

    Kim, Taeg S; Gorski, Stacey A; Hahn, Steven; Murphy, Kenneth M; Braciale, Thomas J

    2014-03-20

    The contribution of different DC subsets to effector and memory CD8(+) T cell generation during infection and the mechanism by which DCs controls these fate decisions is unclear. Here we demonstrated that the CD103(+) and CD11b(hi) migratory respiratory DC (RDC) subsets after influenza virus infection activated naive virus-specific CD8(+) T cells differentially. CD103(+) RDCs supported the generation of CD8(+) T effector (Teff) cells, which migrate from lymph nodes to the infected lungs. In contrast, migrant CD11b(hi) RDCs activated CD8(+) T cells characteristic of central memory CD8(+) T (CD8(+) Tcm) cells including retention within the draining lymph nodes. CD103(+) RDCs expressed CD24 at an elevated level, contributing to the propensity of this DC subpopulation to support CD8(+) Teff cell differentiation. Mechanistically, CD24 was shown to regulate CD8(+) T cell activation through HMGB1-mediated engagement of T cell RAGE. Thus, there is distribution of labor among DC subsets in regulating CD8(+) T cell differentiation.

  14. Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naive and memory T-cell subsets.

    Directory of Open Access Journals (Sweden)

    Willard Tinago

    Full Text Available BACKGROUND: Although effective antiretroviral therapy(ART increases CD4+ T-cell count, responses to ART vary considerably and only a minority of patients normalise their CD4+/CD8+ ratio. Although retention of naïve CD4+ T-cells is thought to predict better immune responses, relationships between CD4+ and CD8+ T-cell subsets and CD4+/CD8+ ratio have not been well described. METHODS: A cross-sectional study in a cohort of ambulatory HIV+ patients. We used flow cytometry on fresh blood to determine expanded CD4+ and CD8+ T-cell subsets; CD45RO+CD62L+(central memory, CD45RO+CD62L-(effector memory and CD45RO-CD62L+(naïve alongside routine T-cell subsets(absolute, percentage CD4+ and CD8+ counts, HIVRNA and collected demographic and treatment data. Relationship between CD4+/CD8+ T-cell ratio and expanded T-cell subsets was determined using linear regression analysis. Results are median[IQR] and regression coefficients unless stated. RESULTS: We recruited 190 subjects, age 42(36-48 years, 65% male, 65.3% Caucasian, 91% on ART(52.6% on protease inhibitors, 78.4% with HIVRNA1. Of the expanded CD4+ T-cell subsets, 27.3(18.0-38.3% were naïve, 36.8(29.0-40.0% central memory and 27.4(20.0-38.5% effector memory. Of the CD8+ T-cells subsets, 16.5(10.2-25.5% were naïve, 19.9(12.7-26.6% central memory and 41.0(31.8-52.5% effector memory. In the multivariable adjusted analysis, total cumulative-ART exposure(+0.15,p = 0.007, higher nadir CD4+ count(+0.011,p1 had significantly higher median %CD8+ naive T-cells; 25.4(14.0-36.0% versus 14.4(9.4-21.6%, p<0.0001, but significantly lower absolute CD8+ count; 464(384.5-567 versus 765(603-1084 cells/mm3, p<0.001. CONCLUSIONS: Study suggests important role for naïve CD8+ T-cell populations in normalisation of the immune response to HIV-infection. How these findings relate to persistent immune activation on ART requires further study.

  15. Commensal Microbe-specific Activation of B2 Cell Subsets Contributes to Atherosclerosis Development Independently of Lipid Metabolism

    Directory of Open Access Journals (Sweden)

    Lin Chen

    2016-11-01

    Full Text Available The relation between B2 cells and commensal microbes during atherosclerosis remains largely unexplored. Here we show that under hyperlipidemic conditions intestinal microbiota resulted in recruitment and ectopic activation of B2 cells in perivascular adipose tissue, followed by an increase in circulating IgG, promoting disease development. In contrast, disruption of the intestinal microbiota by a broad-spectrum antibiotic cocktail (AVNM led to the attenuation of atherosclerosis by suppressing B2 cells, despite the persistence of serum lipid abnormalities. Furthermore, pharmacological depletion of B2 cells with an anti-B2-cell surface CD23 antibody also attenuated commensal microbe-induced atherosclerosis. Moreover, expression analysis of TLR-signaling-related genes in the activated B2 cell subsets, assessed using the Toll-Like Receptor Signaling Pathway RT2 Profiler PCR Array, confirmed activation of the B2-cell autoantibody-production axis, which was associated with an increased capacity of B2 cells to bind to intestinal microbiota. Together, our findings reveal the critical role of commensal microbe-specific activation of B2 cells in the development of atherogenesis through lipid metabolism-independent mechanisms.

  16. T cell subset analysis in peripheral blood of children with RSV bronchiolitis

    NARCIS (Netherlands)

    De Weerd, W; Twilhaar, WN; Kimpen, JLL

    1998-01-01

    Respiratory syncytial virus (RSV) bronchiolitis is partially an immune-mediated disease in which RSV-specific T cells play a predominant role. The peripheral blood T cell response was studied in patients with RSV bronchiolitis in order to detect evidence for T cell redistribution during natural RSV

  17. Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jue Lin

    2016-01-01

    Full Text Available Telomeres, the protective DNA-protein complexes at the ends of linear chromosomes, are important for genome stability. Leukocyte or peripheral blood mononuclear cell (PBMC telomere length is a potential biomarker for human aging that integrates genetic, environmental, and lifestyle factors and is associated with mortality and risks for major diseases. However, only a limited number of studies have examined longitudinal changes of telomere length and few have reported data on sorted circulating immune cells. We examined the average telomere length (TL in CD4+, CD8+CD28+, and CD8+CD28− T cells, B cells, and PBMCs, cross-sectionally and longitudinally, in a cohort of premenopausal women. We report that TL changes over 18 months were correlated among these three T cell types within the same participant. Additionally, PBMC TL change was also correlated with those of all three T cell types, and B cells. The rate of shortening for B cells was significantly greater than for the three T cell types. CD8+CD28− cells, despite having the shortest TL, showed significantly more rapid attrition when compared to CD8+CD28+ T cells. These results suggest systematically coordinated, yet cell type-specific responses to factors and pathways contribute to telomere length regulation.

  18. Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes.

    Science.gov (United States)

    Lin, Jue; Cheon, Joshua; Brown, Rashida; Coccia, Michael; Puterman, Eli; Aschbacher, Kirstin; Sinclair, Elizabeth; Epel, Elissa; Blackburn, Elizabeth H

    2016-01-01

    Telomeres, the protective DNA-protein complexes at the ends of linear chromosomes, are important for genome stability. Leukocyte or peripheral blood mononuclear cell (PBMC) telomere length is a potential biomarker for human aging that integrates genetic, environmental, and lifestyle factors and is associated with mortality and risks for major diseases. However, only a limited number of studies have examined longitudinal changes of telomere length and few have reported data on sorted circulating immune cells. We examined the average telomere length (TL) in CD4+, CD8+CD28+, and CD8+CD28- T cells, B cells, and PBMCs, cross-sectionally and longitudinally, in a cohort of premenopausal women. We report that TL changes over 18 months were correlated among these three T cell types within the same participant. Additionally, PBMC TL change was also correlated with those of all three T cell types, and B cells. The rate of shortening for B cells was significantly greater than for the three T cell types. CD8+CD28- cells, despite having the shortest TL, showed significantly more rapid attrition when compared to CD8+CD28+ T cells. These results suggest systematically coordinated, yet cell type-specific responses to factors and pathways contribute to telomere length regulation.

  19. Dendritic cells in rheumatoid arthritis: Which subset should be used as a tool to induce tolerance?

    NARCIS (Netherlands)

    M.C. Lebre; P.P. Tak

    2009-01-01

    Dendritic cells (DC) comprise a complex network of heterogeneous antigen-presenting cells (APC) that are critical not only to the initiation and regulation of adaptive immunity (Th1/Th2/Th17 responses), but also to the maintenance of both central and peripheral tolerance (regulatory T cells, periphe

  20. T helper cell subsets specific for Pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Hannah K Bayes

    Full Text Available BACKGROUND: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. METHODS: Peripheral blood human memory CD4(+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. RESULTS: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4(+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6(+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. CONCLUSIONS: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions.

  1. Deconvoluting post-transplant immunity: cell subset-specific mapping reveals pathways for activation and expansion of memory T, monocytes and B cells.

    Directory of Open Access Journals (Sweden)

    Yevgeniy A Grigoryev

    Full Text Available A major challenge for the field of transplantation is the lack of understanding of genomic and molecular drivers of early post-transplant immunity. The early immune response creates a complex milieu that determines the course of ensuing immune events and the ultimate outcome of the transplant. The objective of the current study was to mechanistically deconvolute the early immune response by purifying and profiling the constituent cell subsets of the peripheral blood. We employed genome-wide profiling of whole blood and purified CD4, CD8, B cells and monocytes in tandem with high-throughput laser-scanning cytometry in 10 kidney transplants sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. Cytometry confirmed early cell subset depletion by antibody induction and immunosuppression. Multiple markers revealed the activation and proliferative expansion of CD45RO(+CD62L(- effector memory CD4/CD8 T cells as well as progressive activation of monocytes and B cells. Next, we mechanistically deconvoluted early post-transplant immunity by serial monitoring of whole blood using DNA microarrays. Parallel analysis of cell subset-specific gene expression revealed a unique spectrum of time-dependent changes and functional pathways. Gene expression profiling results were validated with 157 different probesets matching all 65 antigens detected by cytometry. Thus, serial blood cell monitoring reflects the profound changes in blood cell composition and immune activation early post-transplant. Each cell subset reveals distinct pathways and functional programs. These changes illuminate a complex, early phase of immunity and inflammation that includes activation and proliferative expansion of the memory effector and regulatory cells that may determine the phenotype and outcome of the kidney transplant.

  2. Langerhans Cell Histiocytosis Involving Maxilla and Mandible

    Directory of Open Access Journals (Sweden)

    M. Guna Shekhar

    2009-06-01

    Full Text Available Langerhans cell histiocytosis is a relatively rare unique disease process characterized by an abnormal proliferation of immature dendritic cells usually affecting children and young adults. Jaws are involved in less than 10% of children with the disease while mandibular involvement in young children is uncommon and bilateral affection is very rare. The purpose of this report is to describe a unique and very rare case of simultaneous and bilateral occurrence of Langerhans cell histiocytosis in both the jaws of a four-year-old boy.

  3. Liver involvement in Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Adelaine; Ortiz-Neira, Clara L.; Abou Reslan, Walid; Kaura, Deepak [Alberta Children' s Hospital, Department of Diagnostic Imaging, Calgary, Alberta (Canada); Sharon, Raphael; Anderson, Ronald [Alberta Children' s Hospital, Department of Oncology, Calgary, AB (Canada); Pinto-Rojas, Alfredo [Alberta Children' s Hospital, Department of Pathology, Calgary, AB (Canada)

    2006-10-15

    Liver involvement in Langerhans cell histiocytosis (LCH) typically presents with hepatomegaly and other signs of liver dysfunction. We present an 11-month-old child having only minimally elevated liver enzymes as an indication of liver involvement. Using sonography as the initial diagnostic tool followed by MRI, LCH of the liver was revealed. A review of sonographic, CT, MRI and MR cholangiopancreatography findings in liver LCH is presented. We recommend that physicians consider sonography and MRI screening for liver involvement in patients with newly diagnosed LCH, as periportal involvement may be present with little or no liver function abnormality present, as in this patient. (orig.)

  4. A Distinct Lung-Interstitium-Resident Memory CD8+ T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection

    Directory of Open Access Journals (Sweden)

    Pavlo Gilchuk

    2016-08-01

    Full Text Available The nature and anatomic location of the protective memory CD8+ T cell subset induced by intranasal vaccination remain poorly understood. We developed a vaccination model to assess the anatomic location of protective memory CD8+ T cells and their role in lower airway infections. Memory CD8+ T cells elicited by local intranasal, but not systemic, vaccination with an engineered non-replicative CD8+ T cell-targeted antigen confer enhanced protection to a lethal respiratory viral challenge. This protection depends on a distinct CXCR3LO resident memory CD8+ T (Trm cell population that preferentially localizes to the pulmonary interstitium. Because they are positioned close to the mucosa, where infection occurs, interstitial Trm cells act before inflammation can recruit circulating memory CD8+ T cells into the lung tissue. This results in a local protective immune response as early as 1 day post-infection. Hence, vaccine strategies that induce lung interstitial Trm cells may confer better protection against respiratory pathogens.

  5. VH1-44 gene usage defines a subset of canine B-cell lymphomas associated with better patient survival.

    Science.gov (United States)

    Chen, Hsiao-Wei; Small, George W; Motsinger-Reif, Alison; Suter, Steven E; Richards, Kristy L

    2014-02-15

    The use of specific immunoglobulin heavy chain variable region (VH) genes has been associated with increased patient survival in human B-cell lymphomas (hBCL). Given the similarity of human and canine BCL (cBCL) in morphology and clinical treatment, we examined the choice of VH in cBCL and determined whether VH gene selection was a distinct feature associated with survival time in dogs. VH gene selection and mutational status in 52 cBCL, including 29 diffuse large B-cell lymphomas (cDLBCL, the most common subtype of cBCL), were analyzed by comparison with the 80 published canine germline VH gene sequences. We further examined the prognostic impact of the subgroups defined by these features on canine survival. We found that VH1-44 was preferentially expressed in the majority of the 52 cBCLs (60%) as well as in the majority of the cDLBCL subset (59%). VH1-44 gene expression was associated with a statistically better overall survival (p=0.039) in cBCL patients, as well as in the cDLBCL subset of patients (p=0.038). These findings suggest that VH gene selection in cBCL is not random and may therefore have functional implications for cBCL lymphomagenesis, in addition to being a useful prognostic biomarker.

  6. Immunohistochemical analysis of small plaque parapsoriasis: involvement of dendritic cells.

    Science.gov (United States)

    Zeybek, N Dilara; Asan, Esin; Erbil, A Hakan; Dagdeviren, Attila

    2008-01-01

    Small plaque parapsoriasis (SPP) is one of the cutaneous T-cell lymphoproliferative disorders. The aim of the present study was to show the antigenic profile of a subset of dendritic cells and lymphocytes in SPP in comparison with normal cells to provide data on the role of these two cell types in the pathogenesis of SPP. Skin biopsy specimens of lesions were obtained from 8 patients with SPP. Biopsies of the healthy skin from 9 control individuals were also analyzed. Immunohistochemistry was performed on the frozen tissue sections to reveal binding of anti-HLA Class II, anti-CD1a, anti-CD4, anti-CD8, anti-CD44, anti-CD45, and anti-CD68 monoclonal antibodies. There was a statistically significant increase in the number of CD1a(+), Langerhans cells (LCs), HLA-DR-immunoreactive and, CD1a-positive dermal dendritic cells and CD68(+) macrophages in the SPP group (p=0.008, 0.008, 0.002 and <0.0009, respectively). The number of lymphocytes positive for CD4, CD8 and CD45 was significantly higher than normal in the SPP group (p=0.015, <0.0009 and <0.0009, respectively). Our study demonstrates that both peptide- and lipid-based antigens are involved in the persistent antigenic exposure in SPP. Dendritic cells play a pivotal role in SPP by presenting antigens by both LC and dermal dendritic cells via MHC Class II and CD1a molecules. The CD68(+) macrophages are thought to be involved in the immune response in this pathology as an antigen-presenting cell.

  7. Altered Expression of Natural Cytotoxicity Receptors and NKG2D on Peripheral Blood NK Cell Subsets in Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Nayeli Goreti Nieto-Velázquez

    2016-10-01

    Full Text Available Human natural killer (NK cells are considered professional cytotoxic cells that are integrated into the effector branch of innate immunity during antiviral and antitumoral responses. The purpose of this study was to examine the peripheral distribution and expression of NK cell activation receptors from the fresh peripheral blood mononuclear cells of 30 breast cancer patients prior to any form of treatment (including surgery, chemotherapy, and radiotherapy, 10 benign breast pathology patients, and 24 control individuals. CD3−CD56dimCD16bright NK cells (CD56dim NK and CD3−CD56brightCD16dim/− NK cells (CD56bright NK were identified using flow cytometry. The circulating counts of CD56dim and CD56bright NK cells were not significantly different between the groups evaluated, nor were the counts of other leukocyte subsets between the breast cancer patients and benign breast pathology patients. However, in CD56dim NK cells, NKp44 expression was higher in breast cancer patients (P = .0302, whereas NKp30 (P = .0005, NKp46 (P = .0298, and NKG2D (P = .0005 expression was lower with respect to healthy donors. In CD56bright NK cells, NKp30 (P = .0007, NKp46 (P = .0012, and NKG2D (P = .0069 expression was lower in breast cancer patients compared with control group. Only NKG2D in CD56bright NK cells (P = .0208 and CD56dim NK cells (P = .0439 showed difference between benign breast pathology and breast cancer patients. Collectively, the current study showed phenotypic alterations in activation receptors on CD56dim and CD56bright NK cells, suggesting that breast cancer patients have decreased NK cell cytotoxicity.

  8. Apoptosis of purified CD4+ T cell subsets is dominated by cytokine deprivation and absence of other cells in new onset diabetic NOD mice.

    Directory of Open Access Journals (Sweden)

    Ayelet Kaminitz

    Full Text Available BACKGROUND: Regulatory T cells (Treg play a significant role in immune homeostasis and self-tolerance. Excessive sensitivity of isolated Treg to apoptosis has been demonstrated in NOD mice and humans suffering of type 1 diabetes, suggesting a possible role in the immune dysfunction that underlies autoimmune insulitis. In this study the sensitivity to apoptosis was measured in T cells from new onset diabetic NOD females, comparing purified subsets to mixed cultures. PRINCIPAL FINDINGS: Apoptotic cells are short lived in vivo and death occurs primarily during isolation, manipulation and culture. Excessive susceptibility of CD25(+ T cells to spontaneous apoptosis is characteristic of isolated subsets, however disappears when death is measured in mixed splenocyte cultures. In variance, CD25(- T cells display balanced sensitivity to apoptosis under both conditions. The isolation procedure removes soluble factors, IL-2 playing a significant role in sustaining Treg viability. In addition, pro- and anti-apoptotic signals are transduced by cell-to-cell interactions: CD3 and CD28 protect CD25(+ T cells from apoptosis, and in parallel sensitize naïve effector cells to apoptosis. Treg viability is modulated both by other T cells and other subsets within mixed splenocyte cultures. Variations in sensitivity to apoptosis are often hindered by fast proliferation of viable cells, therefore cycling rates are mandatory to adequate interpretation of cell death assays. CONCLUSIONS: The sensitivity of purified Treg to apoptosis is dominated by cytokine deprivation and absence of cell-to-cell interactions, and deviate significantly from measurements in mixed populations. Balanced sensitivity of naïve/effector and regulatory T cells to apoptosis in NOD mice argues against the concept that differential susceptibility affects disease evolution and progression.

  9. Mast Cell Subsets and Their Functional Modulation by the Acanthocheilonema viteae Product ES-62

    Directory of Open Access Journals (Sweden)

    Dimity H. Ball

    2013-01-01

    Full Text Available ES-62, an immunomodulator secreted by filarial nematodes, exhibits therapeutic potential in mouse models of allergic inflammation, at least in part by inducing the desensitisation of FcεRI-mediated mast cell responses. However, in addition to their pathogenic roles in allergic and autoimmune diseases, mast cells are important in fighting infection, wound healing, and resolving inflammation, reflecting that mast cells exhibit a phenotypic and functional plasticity. We have therefore characterised the differential functional responses to antigen (via FcεRI and LPS and their modulation by ES-62 of the mature peritoneal-derived mast cells (PDMC; serosal and those of the connective tissue-like mast cells (CTMC and the mucosal-like mast cells derived from bone marrow progenitors (BMMC as a first step to produce disease tissue-targeted therapeutics based on ES-62 action. All three mast cell populations were rendered hyporesponsive by ES-62 and whilst the mechanisms underlying such desensitisation have not been fully delineated, they reflect a downregulation of calcium and PKCα signalling. ES-62 also downregulated MyD88 and PKCδ in mucosal-type BMMC but not PDMC, the additional signals targeted in mucosal-type BMMC likely reflecting that these cells respond to antigen and LPS by degranulation and cytokine secretion whereas PDMC predominantly respond in a degranulation-based manner.

  10. Differential requirement of MALT1 for BAFF-induced outcomes in B cell subsets.

    Science.gov (United States)

    Tusche, Michael W; Ward, Lesley A; Vu, Frances; McCarthy, Doug; Quintela-Fandino, Miguel; Ruland, Jurgen; Gommerman, Jennifer L; Mak, Tak W

    2009-11-23

    B cell activation factor of the TNF family (BAFF) activates noncanonical nuclear factor kappaB (NF-kappaB) heterodimers that promote B cell survival. We show that although MALT1 is largely dispensable for canonical NF-kappaB signaling downstream of the B cell receptor, the absence of MALT1 results in impaired BAFF-induced phosphorylation of NF-kappaB2 (p100), p100 degradation, and RelB nuclear translocation in B220(+) B cells. This corresponds with impaired survival of MALT1(-/-) marginal zone (MZ) but not follicular B cells in response to BAFF stimulation in vitro. MALT1(-/-) MZ B cells also express higher amounts of TRAF3, a known negative regulator of BAFF receptor-mediated signaling, and TRAF3 was found to interact with MALT1. Furthermore, phenotypes associated with overexpression of BAFF, including increased MZ B cell numbers, elevated serum immunoglobulin titers, and spontaneous germinal center formation, were found to be dependent on B cell-intrinsic MALT1 expression. Our results demonstrate a novel role for MALT1 in biological outcomes induced by BAFF-mediated signal transduction.

  11. Granulocytic subset of myeloid derived suppressor cells in rats with mammary carcinoma

    NARCIS (Netherlands)

    Dolen, Y.; Gunaydin, G.; Esendagli, G.; Guc, D.

    2015-01-01

    Limited knowledge is available on myeloid derived suppressor cells (MDSCs) of rat origin. We examined the myeloid cells from peripheral blood, bone marrow and spleens of healthy and mammary tumor bearing rats employing a novel immunophenotyping strategy with CD172a, HIS48, and Rp-1 antibodies. We ad

  12. Cord blood dendritic cell subsets in African newborns exposed to Plasmodium falciparum in utero.

    NARCIS (Netherlands)

    Breitling, L.P.; Fendel, R.; Mordmueller, B.; Adegnika, A.A.; Kremsner, P.G.; Luty, A.J.F.

    2006-01-01

    Placental Plasmodium falciparum infection affects birth outcomes and sensitizes fetal lymphocytes to parasite antigens. We assessed the influence of maternal P. falciparum infection on fetal myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC), analyzing the cord blood of offspring o

  13. First identification of regulatory B cell subsets expressing IL-10 in teleost fish

    Science.gov (United States)

    IL-10 is an immunoregulatory cytokine with a potent anti-inflammatory activity, thus inhibiting the production of proinflammatory cytokines as well as processes of antigen presentation. IL-10 is produced by variety of cells, including antigen presentation cells (i.e., monocytes, macrophages and den...

  14. Beta1 integrins differentially control extravasation of inflammatory cell subsets into the CNS during autoimmunity

    DEFF Research Database (Denmark)

    Bauer, Martina; Brakebusch, Cord; Coisne, Caroline;

    2009-01-01

    Inhibiting the alpha(4) subunit of the integrin heterodimers alpha(4)beta(1) and alpha(4)beta(7) with the monoclonal antibody natalizumab is an effective treatment for multiple sclerosis (MS). However, the pharmacological action of natalizumab is not understood conclusively. Previous studies...... suggested that natalizumab inhibits activation, proliferation, or extravasation of inflammatory cells. To specify which mechanisms, cell types, and alpha(4) heterodimers are affected by the antibody treatment, we studied MS-like experimental autoimmune encephalomyelitis (EAE) in mice lacking the beta(1......)-integrin gene either in all hematopoietic cells or selectively in T lymphocytes. Our results show that T cells critically rely on beta(1) integrins to accumulate in the central nervous system (CNS) during EAE, whereas CNS infiltration of beta(1)-deficient myeloid cells remains unaffected, suggesting that T...

  15. Identifying developmental toxicity pathways for a subset of ToxCast chemicals using human embryonic stem cells and metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Kleinstreuer, N.C., E-mail: kleinstreuer.nicole@epa.gov [NCCT, US EPA, RTP, NC 27711 (United States); Smith, A.M.; West, P.R.; Conard, K.R.; Fontaine, B.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Weir-Hauptman, A.M. [Covance, Inc., Madison, WI 53704 (United States); Palmer, J.A. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Knudsen, T.B.; Dix, D.J. [NCCT, US EPA, RTP, NC 27711 (United States); Donley, E.L.R. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); Cezar, G.G. [Stemina Biomarker Discovery, Inc., Madison, WI 53719 (United States); University of Wisconsin-Madison, Madison, WI 53706 (United States)

    2011-11-15

    Metabolomics analysis was performed on the supernatant of human embryonic stem (hES) cell cultures exposed to a blinded subset of 11 chemicals selected from the chemical library of EPA's ToxCast Trade-Mark-Sign chemical screening and prioritization research project. Metabolites from hES cultures were evaluated for known and novel signatures that may be indicative of developmental toxicity. Significant fold changes in endogenous metabolites were detected for 83 putatively annotated mass features in response to the subset of ToxCast chemicals. The annotations were mapped to specific human metabolic pathways. This revealed strong effects on pathways for nicotinate and nicotinamide metabolism, pantothenate and CoA biosynthesis, glutathione metabolism, and arginine and proline metabolism pathways. Predictivity for adverse outcomes in mammalian prenatal developmental toxicity studies used ToxRefDB and other sources of information, including Stemina Biomarker Discovery's predictive DevTox Registered-Sign model trained on 23 pharmaceutical agents of known developmental toxicity and differing potency. The model initially predicted developmental toxicity from the blinded ToxCast compounds in concordance with animal data with 73% accuracy. Retraining the model with data from the unblinded test compounds at one concentration level increased the predictive accuracy for the remaining concentrations to 83%. These preliminary results on a 11-chemical subset of the ToxCast chemical library indicate that metabolomics analysis of the hES secretome provides information valuable for predictive modeling and mechanistic understanding of mammalian developmental toxicity. -- Highlights: Black-Right-Pointing-Pointer We tested 11 environmental compounds in a hESC metabolomics platform. Black-Right-Pointing-Pointer Significant changes in secreted small molecule metabolites were observed. Black-Right-Pointing-Pointer Perturbed mass features map to pathways critical for normal

  16. Subset- and Antigen-Specific Effects of Treg on CD8+ T Cell Responses in Chronic HIV Infection.

    Science.gov (United States)

    Nikolova, Maria; Wiedemann, Aurélie; Muhtarova, Maria; Achkova, Daniela; Lacabaratz, Christine; Lévy, Yves

    2016-11-01

    We, and others, have reported that in the HIV-negative settings, regulatory CD4+CD25highFoxP3+ T cells (Treg) exert differential effects on CD8 subsets, and maintain the memory / effector CD8+ T cells balance, at least in part through the PD-1/PD-L1 pathway. Here we investigated Treg-mediated effects on CD8 responses in chronic HIV infection. As compared to Treg from HIV negative controls (Treg/HIV-), we show that Treg from HIV infected patients (Treg/HIV+) did not significantly inhibit polyclonal autologous CD8+ T cell function indicating either a defect in the suppressive capacity of Treg/HIV+ or a lack of sensitivity of effector T cells in HIV infection. Results showed that Treg/HIV+ inhibited significantly the IFN-γ expression of autologous CD8+ T cells stimulated with recall CMV/EBV/Flu (CEF) antigens, but did not inhibit HIV-Gag-specific CD8+ T cells. In cross-over cultures, we show that Treg/HIV- inhibited significantly the differentiation of either CEF- or Gag-specific CD8+ T cells from HIV infected patients. The expression of PD-1 and PD-L1 was higher on Gag-specific CD8+ T cells as compared to CEF-specific CD8+ T cells, and the expression of these markers did not change significantly after Treg depletion or co-culture with Treg/HIV-, unlike on CEF-specific CD8+ T cells. In summary, we show a defect of Treg/HIV+ in modulating both the differentiation and the expression of PD-1/PD-L1 molecules on HIV-specific CD8 T cells. Our results strongly suggest that this particular defect of Treg might contribute to the exhaustion of HIV-specific T cell responses.

  17. Apoptosis of Purified CD4+ T Cell Subsets Is Dominated by Cytokine Deprivation and Absence of Other Cells in New Onset Diabetic NOD Mice

    OpenAIRE

    Ayelet Kaminitz; Askenasy, Enosh M.; Isaac Yaniv; Jerry Stein; Nadir Askenasy

    2010-01-01

    BACKGROUND: Regulatory T cells (Treg) play a significant role in immune homeostasis and self-tolerance. Excessive sensitivity of isolated Treg to apoptosis has been demonstrated in NOD mice and humans suffering of type 1 diabetes, suggesting a possible role in the immune dysfunction that underlies autoimmune insulitis. In this study the sensitivity to apoptosis was measured in T cells from new onset diabetic NOD females, comparing purified subsets to mixed cultures. PRINCIPAL FINDINGS: Apopto...

  18. A subset of chondrogenic cells provides early mesenchymal progenitors in growing bones.

    Science.gov (United States)

    Ono, Noriaki; Ono, Wanida; Nagasawa, Takashi; Kronenberg, Henry M

    2014-12-01

    The hallmark of endochondral bone development is the presence of cartilaginous templates, in which osteoblasts and stromal cells are generated to form mineralized matrix and support bone marrow haematopoiesis. However, the ultimate source of these mesenchymal cells and the relationship between bone progenitors in fetal life and those in later life are unknown. Fate-mapping studies revealed that cells expressing cre-recombinases driven by the collagen II (Col2) promoter/enhancer and their descendants contributed to, in addition to chondrocytes, early perichondrial precursors before Runx2 expression and, subsequently, to a majority of osteoblasts, Cxcl12 (chemokine (C-X-C motif) ligand 12)-abundant stromal cells and bone marrow stromal/mesenchymal progenitor cells in postnatal life. Lineage-tracing experiments using a tamoxifen-inducible creER system further revealed that early postnatal cells marked by Col2-creER, as well as Sox9-creER and aggrecan (Acan)-creER, progressively contributed to multiple mesenchymal lineages and continued to provide descendants for over a year. These cells are distinct from adult mesenchymal progenitors and thus provide opportunities for regulating the explosive growth that occurs uniquely in growing mammals.

  19. Transcriptional regulation of cytosol and membrane alanyl-aminopeptidase in human T cell subsets.

    Science.gov (United States)

    Bukowska, Alicja; Tadje, Janine; Arndt, Marco; Wolke, Carmen; Kähne, Thilo; Bartsch, Jaqueline; Faust, Jürgen; Neubert, Klaus; Hashimoto, Yuichi; Lendeckel, Uwe

    2003-04-01

    Aminopeptidase inhibitors strongly affect the proliferation and function of immune cells in man and animals and are promising agents for the pharmacological treatment of inflammatory or autoimmune diseases. Membrane alanyl-aminopeptidase (mAAP) has been considered as the major target of these anti-inflammatory aminopeptidase inhibitors. Recent evidence also points to a role of the cytosol alanyl-aminopeptidase (cAAP) in the immune response. In this study we used quantitative RT-PCR to determine the mRNA expression of both cAAP and mAAP in resting and activated peripheral T cells and also in CD4+, CD8+, Th1, Th2 and Treg (CD4+ CD25+) subpopulations. Both mAAP and cAAP mRNAs were expressed in all cell types investigated, and in response to activation their expression appeared to be upregulated in CD8+ cells, but downregulated in Treg cells. In CD4+ cells, mAAP and cAAP mRNAs were affected in opposite ways in response to activation. The cAAP-specific inhibitor, PAQ-22, did not affect either cAAP or mAAP expression in activated CD4+ or CD8+ cells, whereas in activated Treg cells it markedly upregulated the mRNA levels of both aminopeptidases. The non-discriminatory inhibitor, phebestin, significantly increased the amount of mAAP and cAAP mRNA in CD4+ and that of cAAP in Treg cells.

  20. Variation of T cell subset during acute rejection after liver transplantation in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Ran Jiang-hua; Liu Jing; Zhang Xi-bing; Zhang Sheng-ning; Wu Shu-yuan; Li Lai-bang; Li Wang; Li Li

    2014-01-01

    Abstract BACKGROUND: Looking for the early diagnosis of acute rejection indicators after liver transplantation can assess the risk after liver transplantation quickly and effectively, and T lymphocytes play the significant role in acute rejection. OBJECTIVE:To observe the relationship between acute rejection and variation of expression of T cel subset in blood after liver transplantation in rhesus monkey. METHODS: The sixteen liver transplant models in rhesus monkey which were constructed successfuly by the method of “double-cuff and one support tube” were divided into two groups randomly: experiment group (no treated by immunosuppressant in perioperative period) and control group (treated by immunosuppressant in perioperative period). Then the blood specimen and liver tissue respectively were colected at 6, 12, 24 and 72 hours after operation. The levels of alanine transferase, aspartate aminotransferase, and total bilirubin were detected with the fuly automatic biochemical analyser. The levels of CD4+/CD8+were tested by flow cytometry. The liver tissue in rhesus monkey after liver transplantation was detected by hematoxylin-eosin staining. The degree of acute rejection was evaluated by Banff Score System. RESULTS AND CONCLUSION: Acute rejection appeared in the experiment group at 12, 24, and 72 hours after liver transplantation. Levels of alanine transferase, aspartate aminotransferase, and total bilirubin were significantly higher in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). The expression of CD4+/CD8+of the experiment group and control group began to rise at 6 hours after surgery, but the experiment group increased the most obvious. CD4+/CD8+ expression was significantly greater in the experimental group than in the control group at 24 and 72 hours after transplantation (P < 0.05). Morphological pathology was severer, and Banff score was higher in the experiment group than in the control group at

  1. A single HIV-1 cluster and a skewed immune homeostasis drive the early spread of HIV among resting CD4+ cell subsets within one month post-infection.

    Science.gov (United States)

    Bacchus, Charline; Cheret, Antoine; Avettand-Fenoël, Véronique; Nembot, Georges; Mélard, Adeline; Blanc, Catherine; Lascoux-Combe, Caroline; Slama, Laurence; Allegre, Thierry; Allavena, Clotilde; Yazdanpanah, Yazdan; Duvivier, Claudine; Katlama, Christine; Goujard, Cécile; Seksik, Bao Chau Phung; Leplatois, Anne; Molina, Jean-Michel; Meyer, Laurence; Autran, Brigitte; Rouzioux, Christine

    2013-01-01

    Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI). We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM]) and short-lived (transitional-memory [TTM] and effector-memory cells [TEM]) resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells), although 10-fold less (p = 0.0005) than in equally infected TCM (4.5), TTM (4.7) and TEM (4.6) cells. CD3-CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells), unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells). The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility, suggesting that

  2. A single HIV-1 cluster and a skewed immune homeostasis drive the early spread of HIV among resting CD4+ cell subsets within one month post-infection.

    Directory of Open Access Journals (Sweden)

    Charline Bacchus

    Full Text Available Optimizing therapeutic strategies for an HIV cure requires better understanding the characteristics of early HIV-1 spread among resting CD4+ cells within the first month of primary HIV-1 infection (PHI. We studied the immune distribution, diversity, and inducibility of total HIV-DNA among the following cell subsets: monocytes, peripheral blood activated and resting CD4 T cells, long-lived (naive [TN] and central-memory [TCM] and short-lived (transitional-memory [TTM] and effector-memory cells [TEM] resting CD4+T cells from 12 acutely-infected individuals recruited at a median 36 days from infection. Cells were sorted for total HIV-DNA quantification, phylogenetic analysis and inducibility, all studied in relation to activation status and cell signaling. One month post-infection, a single CCR5-restricted viral cluster was massively distributed in all resting CD4+ subsets from 88% subjects, while one subject showed a slight diversity. High levels of total HIV-DNA were measured among TN (median 3.4 log copies/million cells, although 10-fold less (p = 0.0005 than in equally infected TCM (4.5, TTM (4.7 and TEM (4.6 cells. CD3-CD4+ monocytes harbored a low viral burden (median 2.3 log copies/million cells, unlike equally infected resting and activated CD4+ T cells (4.5 log copies/million cells. The skewed repartition of resting CD4 subsets influenced their contribution to the pool of resting infected CD4+T cells, two thirds of which consisted of short-lived TTM and TEM subsets, whereas long-lived TN and TCM subsets contributed the balance. Each resting CD4 subset produced HIV in vitro after stimulation with anti-CD3/anti-CD28+IL-2 with kinetics and magnitude varying according to subset differentiation, while IL-7 preferentially induced virus production from long-lived resting TN cells. In conclusion, within a month of infection, a clonal HIV-1 cluster is massively distributed among resting CD4 T-cell subsets with a flexible inducibility

  3. GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine

    DEFF Research Database (Denmark)

    Mortensen, Kristine; Christensen, Louise Lundby; Holst, Jens Juul;

    2003-01-01

    BACKGROUND: The incretin hormones GIP and GLP-1 are thought to be produced in separate endocrine cells located in the proximal and distal ends of the mammalian small intestine, respectively. METHODS AND RESULTS: Using double immunohistochemistry and in situ hybridization, we found that GLP-1...... was colocalized with either GIP or PYY in endocrine cells of the porcine, rat, and human small intestines, whereas GIP and PYY were rarely colocalized. Thus, of all the cells staining positively for either GLP-1, GIP, or both, 55-75% were GLP-1 and GIP double-stained in the mid-small intestine. Concentrations...... of extractable GIP and PYY were highest in the midjejunum [154 (95-167) and 141 (67-158) pmol/g, median and range, respectively], whereas GLP-1 concentrations were highest in the ileum [92 (80-207) pmol/l], but GLP-1, GIP, and PYY immunoreactive cells were found throughout the porcine small intestine...

  4. Osteoarticular involvement in sickle cell disease

    Directory of Open Access Journals (Sweden)

    Geraldo Bezerra da Silva Junior

    2012-01-01

    Full Text Available The osteoarticular involvement in sickle cell disease has been poorly studied and it is mainly characterized by osteonecrosis, osteomyelitis and arthritis. The most frequent complications and those that require hospital care in sickle cell disease patients are painful vaso-occlusive crises and osteomyelitis. The deoxygenation and polymerization of hemoglobin S, which results in sickling and vascular occlusion, occur more often in tissues with low blood flow, such as in the bones. Bone microcirculation is a common place for erythrocyte sickling, which leads to thrombosis, infarct and necrosis. The pathogenesis of microvascular occlusion, the key event in painful crises, is complex and involves activation of leukocytes, platelets and endothelial cells, as well as hemoglobin S-containing red blood cells. Osteonecrosis is a frequent complication in sickle cell disease, with a painful and debilitating pattern. It is generally insidious and progressive, affecting mainly the hips (femur head and shoulders (humeral head. Dactylitis, also known as hand-foot syndrome, is an acute vaso-occlusive complication characterized by pain and edema in both hands and feet, frequently with increased local temperature and erythema. Osteomyelitis is the most common form of joint infection in sickle cell disease. The occurrence of connective tissue diseases, including rheumatoid arthritis and systemic lupus erythematosus, has rarely been reported in patients with sickle cell disease. The treatment of these complications is mainly symptomatic, and more detailed studies are required to understand the pathophysiological mechanisms involved in the complications and propose more adequate and specific therapies.

  5. Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Aaron Topol

    2016-05-01

    Full Text Available Converging evidence indicates that microRNAs (miRNAs may contribute to disease risk for schizophrenia (SZ. We show that microRNA-9 (miR-9 is abundantly expressed in control neural progenitor cells (NPCs but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.

  6. Dysregulation of miRNA-9 in a Subset of Schizophrenia Patient-Derived Neural Progenitor Cells.

    Science.gov (United States)

    Topol, Aaron; Zhu, Shijia; Hartley, Brigham J; English, Jane; Hauberg, Mads E; Tran, Ngoc; Rittenhouse, Chelsea Ann; Simone, Anthony; Ruderfer, Douglas M; Johnson, Jessica; Readhead, Ben; Hadas, Yoav; Gochman, Peter A; Wang, Ying-Chih; Shah, Hardik; Cagney, Gerard; Rapoport, Judith; Gage, Fred H; Dudley, Joel T; Sklar, Pamela; Mattheisen, Manuel; Cotter, David; Fang, Gang; Brennand, Kristen J

    2016-05-01

    Converging evidence indicates that microRNAs (miRNAs) may contribute to disease risk for schizophrenia (SZ). We show that microRNA-9 (miR-9) is abundantly expressed in control neural progenitor cells (NPCs) but also significantly downregulated in a subset of SZ NPCs. We observed a strong correlation between miR-9 expression and miR-9 regulatory activity in NPCs as well as between miR-9 levels/activity, neural migration, and diagnosis. Overexpression of miR-9 was sufficient to ameliorate a previously reported neural migration deficit in SZ NPCs, whereas knockdown partially phenocopied aberrant migration in control NPCs. Unexpectedly, proteomic- and RNA sequencing (RNA-seq)-based analysis revealed that these effects were mediated primarily by small changes in expression of indirect miR-9 targets rather than large changes in direct miR-9 targets; these indirect targets are enriched for migration-associated genes. Together, these data indicate that aberrant levels and activity of miR-9 may be one of the many factors that contribute to SZ risk, at least in a subset of patients.

  7. A mechanism for TCR sharing between T cell subsets and individuals revealed by pyrosequencing.

    Science.gov (United States)

    Venturi, Vanessa; Quigley, Máire F; Greenaway, Hui Yee; Ng, Pauline C; Ende, Zachary S; McIntosh, Tina; Asher, Tedi E; Almeida, Jorge R; Levy, Samuel; Price, David A; Davenport, Miles P; Douek, Daniel C

    2011-04-01

    The human naive T cell repertoire is the repository of a vast array of TCRs. However, the factors that shape their hierarchical distribution and relationship with the memory repertoire remain poorly understood. In this study, we used polychromatic flow cytometry to isolate highly pure memory and naive CD8(+) T cells, stringently defined with multiple phenotypic markers, and used deep sequencing to characterize corresponding portions of their respective TCR repertoires from four individuals. The extent of interindividual TCR sharing and the overlap between the memory and naive compartments within individuals were determined by TCR clonotype frequencies, such that higher-frequency clonotypes were more commonly shared between compartments and individuals. TCR clonotype frequencies were, in turn, predicted by the efficiency of their production during V(D)J recombination. Thus, convergent recombination shapes the TCR repertoire of the memory and naive T cell pools, as well as their interrelationship within and between individuals.

  8. Study on T lymphocyte subsets and NK cells in patients with Graves' disease combined with type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Wei Feng; Du Jing; Su Xiulan; Wu Lan; Wang Jinjing; Huo Xiaojing

    2008-01-01

    Objective To investigate changes in T lymphocyte subsets and NK cells in patients with simple Graves' disease (GD)and Graves' disease combined with type 2 diabetes mellitus (GD/T2DM). Methods Fifteen cases of GD/ T2DM were selected from our hospital from November 2001 to November 2004. Before and after therapy thyroid function, thyroglobulin antibody (TGA), thyroid microsomal antibody (TMA) and blood glucose level were measured, and T lymphocyte subsets (CD3, CD4, CD8, CD4/CD8) and NK cells (CD56) were measured by immunofluorescence double labeling monoclonal antibody and flow cytometry, respectively. At the same time, comparison was made with simple GD (15 cases), T2DM (15 cases) and healthy control (20 cases). Results Before therapy, CD4/CD8, CD4 and NK cells in GD/T2DM were less than normal, and there was no significant difference in comparison with simple GD (P<0.05). In T2DM group, only CD4/CD8 and CD4 were less than those of healthy controls (P<0.05). When thyroid function recovered after 1 to 3 months of methimazole treatment in both GD/T2DM and simple GD groups, various indexes recovered, which were more obvious in simple GD. Conclusion Immune hypofunction of GD may be the key to the immune abnormality of GD/T2DM, which is more significant than that of simple GD or T2DM. The recovery of thyroid function and immune abnormality is not consistent, and the recovery of GD is more significant than that of GD/T2DM.

  9. Distinct T cell signatures define subsets of patients with multiple sclerosis

    Science.gov (United States)

    Johnson, Mark C.; Pierson, Emily R.; Spieker, Andrew J.; Nielsen, A. Scott; Posso, Sylvia; Kita, Mariko; Buckner, Jane H.

    2016-01-01

    Objective: We investigated T cell responses to myelin proteins in the blood of healthy controls and 2 groups of patients with relapsing-remitting multiple sclerosis (RRMS) who exhibited lesions either predominantly in the brain or predominantly in the spinal cord in order to assess whether distinct neuroinflammatory patterns were associated with different myelin protein–specific T cell effector function profiles and whether these profiles differed from healthy controls. Methods: Peripheral blood mononuclear cells were obtained from patients with brain-predominant RRMS, patients with spinal cord–predominant RRMS, and age-matched healthy controls and analyzed by enzyme-linked immunosorbent spot assays to quantify interferon gamma–secreting (Th1) and interleukin 17–secreting (Th17) cells responding directly ex vivo to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG). Results: Although MBP and MOG elicited different responses, patients with multiple sclerosis (MS) who had spinal cord–predominant lesions exhibited significantly higher Th17:Th1 ratios in response to both MBP and MOG compared to patients with brain-predominant MS. Incorporating the cytokine responses to both antigens into logistic regression models showed that these cytokine responses were able to provide good discrimination between patients with distinct neuroinflammatory patterns. Conclusions: Our findings suggest that the localization of lesions within the brain vs the spinal cord in patients with MS is associated with different effector T cell responses to myelin proteins. Further investigation of the relationship between T cell effector function, antigen specificities, and lesion sites may reveal features of pathogenic pathways that are distinct to patients with different neuroinflammatory patterns. PMID:27606354

  10. Sub-sets of cancer stem cells differ intrinsically in their patterns of oxygen metabolism.

    Directory of Open Access Journals (Sweden)

    Luke Gammon

    Full Text Available The glycolytic response of hypoxic cells is primarily mediated by the hypoxia inducible factor alpha (HIF-1α but even in the presence of abundant oxygen tumours typically show high rates of glycolysis. Higher levels of HIF-1α in tumours are associated with a poorer prognosis and up-regulation of markers of epithelial mesenchymal transition (EMT due to HIF-1α actions. We have recently shown that EMT occurs within the CD44(high cancer stem cell (CSC fraction and that epithelial and EMT CSCs are distinguished by high and low ESA expression, respectively. We here show that hypoxia induces a marked shift of the CSC fraction towards EMT leading to altered cell morphology, an increased proportion of CD44(high/ESA(low cells, patterns of gene expression typical of EMT, and enhanced sphere-forming ability. The size of EMT fractions returned to control levels in normoxia indicating a reversible process. Surprisingly, however, even under normoxic conditions a fraction of EMT CSCs was present and maintained high levels of HIF-1α, apparently due to actions of cytokines such as TNFα. Functionally, this EMT CSC fraction showed decreased mitochondrial mass and membrane potential, consumed far less oxygen per cell, and produced markedly reduced levels of reactive oxygen species (ROS. These differences in the patterns of oxygen metabolism of sub-fractions of tumour cells provide an explanation for the general therapeutic resistance of CSCs and for the even greater resistance of EMT CSCs. They also identify potential mechanisms for manipulation of CSCs.

  11. Glial cells are involved in itch processing

    DEFF Research Database (Denmark)

    Andersen, Hjalte H.; Arendt-Nielsen, Lars; Gazerani, Parisa

    2016-01-01

    Recent discoveries in itch neurophysiology include itch-selective neuronal pathways, the clinically relevant non-histaminergic pathway, and elucidation of the notable similarities and differences between itch and pain. Potential involvement of glial cells in itch processing and the possibility...

  12. Cord blood dendritic cell subsets in African newborns exposed to Plasmodium falciparum in utero.

    Science.gov (United States)

    Breitling, Lutz P; Fendel, Rolf; Mordmueller, Benjamin; Adegnika, Ayola A; Kremsner, Peter G; Luty, Adrian J F

    2006-10-01

    Placental Plasmodium falciparum infection affects birth outcomes and sensitizes fetal lymphocytes to parasite antigens. We assessed the influence of maternal P. falciparum infection on fetal myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC), analyzing the cord blood of offspring of Gabonese mothers with different infection histories. Cord blood from newborns of mothers with malarial infection at delivery had significantly more mDC than that from nonexposed newborns (P = 0.028) but mDC and pDC HLA-DR expression was unrelated to maternal infection history. Independently of these findings, cord blood mDC and pDC numbers declined significantly as a function of increasing maternal age (P = 0.029 and P = 0.033, respectively). The inducible antigen-specific interleukin-10-producing regulatory-type T-cell population that we have previously detected in cord blood of newborns with prolonged in utero exposure to P. falciparum may directly reflect the altered DC numbers in such neonates, while the maintenance of cord blood DC HLA-DR expression contrasts with that of DC from P. falciparum malaria patients.

  13. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Stivarou, Theodora; Patsavoudi, Evangelia, E-mail: epatsavoudi@pasteur.gr [Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521 (Greece); Technological Educational Institute of Athens, Egaleo, Athens 12210 (Greece)

    2015-01-26

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  14. Extracellular Molecules Involved in Cancer Cell Invasion

    Directory of Open Access Journals (Sweden)

    Theodora Stivarou

    2015-01-01

    Full Text Available Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  15. A subset of prostatic basal cell carcinomas harbor the MYB rearrangement of adenoid cystic carcinoma.

    Science.gov (United States)

    Bishop, Justin A; Yonescu, Raluca; Epstein, Jonathan I; Westra, William H

    2015-08-01

    Adenoid cystic carcinoma (ACC) is a basaloid tumor consisting of myoepithelial and ductal cells typically arranged in a cribriform pattern. Adenoid cystic carcinoma is generally regarded as a form of salivary gland carcinoma, but it can arise from sites unassociated with salivary tissue. A rare form of prostate carcinoma exhibits ACC-like features; it is no longer regarded as a true ACC but rather as prostatic basal cell carcinoma (PBCC) and within the spectrum of basaloid prostatic proliferations. True ACCs often harbor MYB translocations resulting in the MYB-NFIB fusion protein. MYB analysis could clarify the true nature of prostatic carcinomas that exhibit ACC features and thus help refine the classification of prostatic basaloid proliferations. Twelve PBCCs were identified from the pathology consultation files of Johns Hopkins Hospital. The histopathologic features were reviewed, and break-apart fluorescence in situ hybridization for MYB was performed. All 12 cases exhibited prominent basaloid histology. Four were purely solid, 7 exhibited a cribriform pattern reminiscent of salivary ACC, and 1 had a mixed pattern. The MYB rearrangement was detected in 2 (29%) of 7 ACC-like carcinomas but in none (0%) of the 5 PBCCs with a prominent solid pattern. True ACCs can arise in the prostate as is evidenced by the presence of the characteristic MYB rearrangement. When dealing with malignant basaloid proliferations in the prostate, recommendations to consolidate ACCs with other tumor types may need to be reassessed, particularly in light of the rapidly advancing field of biologic therapy where the identification of tumor-specific genetic alterations presents novel therapeutic targets.

  16. Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets

    Science.gov (United States)

    Pensieroso, Simone; Tolazzi, Monica; Chiappetta, Stefania; Nozza, Silvia; Lazzarin, Adriano; Tambussi, Giuseppe; Scarlatti, Gabriella

    2015-01-01

    Introduction During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART). Materials and Methods To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation. Results Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups. Conclusions In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization

  17. Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

    Directory of Open Access Journals (Sweden)

    Manuela Pogliaghi

    Full Text Available During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART.To investigate the impact of infection as early as during primary HIV-1 infection (PHI we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI individuals before and during 48 weeks of cART as compared to healthy controls (n = 23. We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation.Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM, Tissue-like Memory (TLM B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD- phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups.In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized

  18. SORAFENIB FOR OLDER PATIENTS WITH RENAL CELL CARCINOMA: SUBSET ANALYSIS FROM A RANDOMIZED TRIAL

    Directory of Open Access Journals (Sweden)

    T. Eisen

    2014-08-01

    Full Text Available Background. The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy.Methods.  This retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age ≥ 70 years, n = 115 and younger patients (age <70 years, n = 787 who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease, time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportion- al hazards model. Kaplan - Meier analyses were used to summarize time-to-event data.Results. Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66 and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69. Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively. Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03 and younger patients (90 days with sorafenib vs 52 days with placebo

  19. SORAFENIB FOR OLDER PATIENTS WITH RENAL CELL CARCINOMA: SUBSET ANALYSIS FROM A RANDOMIZED TRIAL

    Directory of Open Access Journals (Sweden)

    T. Eisen

    2009-01-01

    Full Text Available Background. The perception that older cancer patients may be at higher risk than younger patients of toxic effects from cancer therapy but may obtain less clinical benefit from it may be based on the underrepresentation of older patients in clinical trials and the known toxic effects of cytotoxic chemotherapy. It is not known how older patients respond to targeted therapy.Methods.  This retrospective subgroup analysis of data from the phase 3, randomized Treatment Approach in Renal Cancer Global Evaluation Trial examined the safety and efficacy of sorafenib in older (age ≥ 70 years, n = 115 and younger patients (age <70 years, n = 787 who received treatment for advanced renal cell carcinoma. Patient demographics and progression-free survival were recorded. Best tumor response, clinical benefit rate (defined as complete response plus partial response plus stable disease, time to self-reported health status deterioration, and toxic effects were assessed by descriptive statistics. Health-related quality of life was assessed with a Cox proportion- al hazards model. Kaplan - Meier analyses were used to summarize time-to-event data.Results. Median progression-free survival was similar in sorafenib-treated younger patients (23.9 weeks; hazard ratio [HR] for progression compared with placebo = 0.55, 95% confidence interval [CI] = 0.47 to 0.66 and older patients (26.3 weeks; HR = 0.43, 95% CI = 0.26 to 0.69. Clinical benefit rates among younger and older sorafenib-treated patients were also similar (83.5% and 84.3%, respectively and were superior to those of younger and older placebo-treated patients (53.8% and 62.2%, respectively. Adverse events were predictable and manageable regardless of age. Sorafenib treatment delayed the time to self-reported health status deterioration among both older patients (121 days with sorafenib vs 85 days with placebo; HR = 0.66, 95% CI = 0.43 to 1.03 and younger patients (90 days with sorafenib vs 52 days with placebo

  20. CD38 Expression in a Subset of Memory T Cells Is Independent of Cell Cycling as a Correlate of HIV Disease Progression

    Directory of Open Access Journals (Sweden)

    Daniela Würsch

    2016-01-01

    Full Text Available In order to determine if the expression of the activation marker CD38 can correlate with HIV disease progression independently of cycling, we performed a cluster-based multivariate correlation analysis of total circulating CD4+ T cell counts and viral loads with frequencies of CD38 and Ki67 expression on CD4+ lymphocytes from patients with untreated HIV infection, stratified in maturation subpopulations, and subpopulation subsets defined by the expression of CXCR5, CXCR3, and CCR4. The frequencies of the activated phenotypes %CD38+ Ki67− and %CD38+ Ki67+ of the CXCR5− CXCR3− CCR4+ (“pre-Th2” central memory (TCM cell subset clustered together, comprising a significant negative correlate of total circulating CD4+ T cell counts and a positive correlate of viral load in multivariate analysis. Frequency of cycling-uncoupled CD38 expression in “pre-Th2” TCM cells was a negative correlate of total circulating CD4+ T cell counts in univariate analysis, which was not the case of their %CD38+ Ki67+. CXCR5+ CXCR3− CCR4−  TCM cells were underrepresented in patients, and their absolute counts correlated negatively with their %CD38+ Ki67− but not with their % CD38+ Ki67+. Our results may imply that CD38 expression either reflects or participates in pathogenic mechanisms of HIV disease independently of cell cycling.

  1. Nailfold videocapillaroscopy in systemic sclerosis: diagnostic and follow-up parameters and correlation with both specific serum autoantibodies and subsets of skin involvement

    Directory of Open Access Journals (Sweden)

    B. Seriolo

    2011-09-01

    Full Text Available Introduction: The aim of the present study was to demonstrate, by nailfold videocapillaroscopy (NVC, the existence of diagnostic and follow-up parameters of microvascular damage in systemic sclerosis (SS (grouped in the “early”, “active” and “late” NVC patterns. The presence of the different subsets of skin involvement (limSS and difSS, as well as the role of some specific serum autoantibodies in the expression of the NVC parameters were investigated. Methods: 245 consecutive SS patients were recruited and clinical data assessed. Antinuclear (ANA, antitopoisomerase I (Scl70 and anticentromere (ACA antibodies were investigated in all patients. Results: Giant capillaries and hemorrhages were confirmed to be the earliest NVC finding in SS (diagnostic parameters. The loss of capillaries, along with ramified capillaries and vascular architectural disorganization were validated as parameters of progression of SS microangiopathy. Really, both Raynaud’s phenomenon (RP and SS duration were detected longer in patients with the “late” than in those with the “active” or the “early” NVC pattern. Patients affected by limSS were found to have shorter disease duration, as well as showed more frequently the “early” or the “active” NVC patterns. Conversely, patients affected by the difSS showed longer disease duration and mostly the presence of the “active” or “late” NVC pattern. The Scl70 positivity was lower in the patients showing the “early” than in those with the “active” and the “late” NVC patterns, whereas no significant correlation was found between the Scl70 presence and both RP and SS duration. The ACA positivity was higher in patients showing the “early” NVC pattern, as well as in patients with longer disease duration. Conclusions: This study confirms that the identification of distinct NVC patterns may be useful to evaluate the severity and the stage of the SS microvascular damage. The presence

  2. Characterization of effector and memory T cell subsets in the immune response to bovine tuberculosis in cattle.

    Directory of Open Access Journals (Sweden)

    Mayara F Maggioli

    Full Text Available Cultured IFN-γ ELISPOT assays are primarily a measure of central memory T cell (Tcm responses with humans; however, this important subset of lymphocytes is poorly characterized in cattle. Vaccine-elicited cultured IFN-γ ELISPOT responses correlate with protection against bovine tuberculosis in cattle. However, whether this assay measures cattle Tcm responses or not is uncertain. The objective of the present study was to characterize the relative contribution of Tcm (CCR7+, CD62Lhi, CD45RO+, T effector memory (Tem, defined as: CCR7-, CD62Llow/int, CD45RO+, and T effector cells (CCR7-, CD62L-/low, CD45RO-, in the immune response to Mycobacterium bovis. Peripheral blood mononuclear cells (PBMC from infected cattle were stimulated with a cocktail of M. bovis purified protein derivative, rTb10.4 and rAg85A for 13 days with periodic addition of fresh media and rIL-2. On day 13, cultured PBMC were re-stimulated with medium alone, rESAT-6:CFP10 or PPDb with fresh autologous adherent cells for antigen presentation. Cultured cells (13 days or fresh PBMCs (ex vivo response from the same calves were analyzed for IFN-γ production, proliferation, and CD4, CD45RO, CD62L, CD44, and CCR7 expression via flow cytometry after overnight stimulation. In response to mycobacterial antigens, ~75% of CD4+ IFN-γ+ cells in long-term cultures expressed a Tcm phenotype while less than 10% of the ex vivo response consisted of Tcm cells. Upon re-exposure to antigen, long-term cultured cells were highly proliferative, a distinctive characteristic of Tcm, and the predominant phenotype within the long-term cultures switched from Tcm to Tem. These findings suggest that proliferative responses of Tcm cells to some extent occurs simultaneously with reversion to effector phenotypes (mostly Tem. The present study characterizes Tcm cells of cattle and their participation in the response to M. bovis infection.

  3. Neonatal colonisation expands a specific intestinal antigen-presenting cell subset prior to CD4 T-cell expansion, without altering T-cell repertoire.

    Directory of Open Access Journals (Sweden)

    Charlotte F Inman

    Full Text Available Interactions between the early-life colonising intestinal microbiota and the developing immune system are critical in determining the nature of immune responses in later life. Studies in neonatal animals in which this interaction can be examined are central to understanding the mechanisms by which the microbiota impacts on immune development and to developing therapies based on manipulation of the microbiome. The inbred piglet model represents a system that is comparable to human neonates and allows for control of the impact of maternal factors. Here we show that colonisation with a defined microbiota produces expansion of mucosal plasma cells and of T-lymphocytes without altering the repertoire of alpha beta T-cells in the intestine. Importantly, this is preceded by microbially-induced expansion of a signal regulatory protein α-positive (SIRPα(+ antigen-presenting cell subset, whilst SIRPα(-CD11R1(+ antigen-presenting cells (APCs are unaffected by colonisation. The central role of intestinal APCs in the induction and maintenance of mucosal immunity implicates SIRPα(+ antigen-presenting cells as orchestrators of early-life mucosal immune development.

  4. The effect of valtrex on T cell subset and IL2, IL6 and IL10 level in patients with herpes zoster

    Institute of Scientific and Technical Information of China (English)

    Gui-E Wang; Jian Chen; Ling Chen

    2015-01-01

    Objective:To explore the effects of valtrex on T cell subset and IL2, IL6 and IL10 level in patients with herpes zoster.Methods: 120 patients with herpes zoster in our hospital were analyzed. The serum T cell subset and IL2, IL6 and IL10 were detected by Western Blotting. Healthy volunteers were enrolled as control group.Results: The CD4+ level was increased significantly while the CD8+ decreased significantly, and the ratio of the two increased too (P all<0.01). The IL6 and IL10 levels were increased significantly (P<0.01). But no significant change in IL2 level was observed.Conclusion:Valtrex is effective on herpes zoster by regulating T cell subset, IL6 and IL10 levels.

  5. Circulating and Tumor-Infiltrating Foxp3+ Regulatory T Cell Subset in Chinese Patients with Extranodal NK/T Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Rou-Jun Peng, Zhou-Feng Huang, Yi-Lan Zhang, Zhong-Yu Yuan, Yi Xia, Wen-Qi Jiang, Yi-Xin Zeng, Jiang Li

    2011-01-01

    Full Text Available Foxp3+ regulatory T lymphocytes (Tregs usually act as an immune suppressor and correlate with poorer survival in malignancies. This study aims to investigate the distribution and characterization of Foxp3+ subset in peripheral blood mononuclear cells (PBMCs and tumor tissues from extranodal NK/T cell lymphoma (ENKTL. Our study showed the percentage of Foxp3+ subset from PBMC was significantly higher than that of healthy individuals (P<0.001. The Foxp3+ subset from PBMCs expressed CD45RO, CTLA4, GITR, CCR7, and had an IL-10highIFNγ+TGFβ+IL-2lowIL-17low cytokine secreting phenotype. Interestingly, the existence of EBV antigen-specific CD8+Foxp3+ Tregs was discovered in ENKTL. Furthermore, the high density of Foxp3+ TILs was associated with improved progression-free survival (PFS in ENKTL patients (P<0.05. Collectively, our study implicates that EBV antigens could induce antigen-specific CD8+Foxp3+ Tregs in ENKTL, and Foxp3+ TILs is an independent factor for PFS in ENKTL.

  6. Influence of melatonin therapy and orchiectomy on T cell subsets in male Wistar rats infected with Trypanosoma cruzi.

    Science.gov (United States)

    Santello, Fabricia H; Del Vecchio Filipin, Marina; Caetano, Leony C; Brazão, Vânia; Caetano, Luana N; Dos Santos, Carla D; Alonso Toldo, Míriam P; do Prado, José C

    2009-10-01

    Gonadal steroids exert an important influence on the host immune response during infection. Changes resulting from the absence or replacement of gonadal hormones may represent a distinct evolution of a particular parasite. Taking into account the greater susceptibility of males to parasites, the magnitude of the immune response seems to depend on the interaction of many hormones that will act synergistically with other immune cells. The aims of this research were to evaluate the effects of the luck of male sex hormones due to orchiectomy, and the influence of oral administration of melatonin on the immune response of male Wistar rats infected with the Y strain of Trypanosoma cruzi. The percentage of CD3(+) CD4(+) and CD3(+) CD8(+) lymphocyte T cell subsets were evaluated using flow cytometry and the measurement of IL-2 and IL-12. For all parameters examined, a synergistic action of melatonin and orchiectomy on the host's immune response was observed, promoting an effective response against the parasite during the acute phase of infection. These results offer insight into other possibilities for possibly controlling T. cruzi proliferation through melatonin therapy and also the stimulatory effects on host's immune response triggered by the absence of male gonadal steroids during the acute phase of infection.

  7. Localization of Distinct Peyer's Patch Dendritic Cell Subsets and Their Recruitment by Chemokines Macrophage Inflammatory Protein (Mip)-3α, Mip-3β, and Secondary Lymphoid Organ Chemokine

    Science.gov (United States)

    Iwasaki, Akiko; Kelsall, Brian L.

    2000-01-01

    We describe the anatomical localization of three distinct dendritic cell (DC) subsets in the murine Peyer's patch (PP) and explore the role of chemokines in their recruitment. By two-color in situ immunofluorescence, CD11b+ myeloid DCs were determined to be present in the subepithelial dome (SED) region, whereas CD8α+ lymphoid DCs are present in the T cell–rich interfollicular region (IFR). DCs that lack expression of CD8α or CD11b (double negative) are present in both the SED and IFR. By in situ hybridization, macrophage inflammatory protein (MIP)-3α mRNA was dramatically expressed only by the follicle-associated epithelium overlying the SED, while its receptor, CCR6, was concentrated in the SED. In contrast, CCR7 was expressed predominantly in the IFR. Consistent with these findings, reverse transcriptase polymerase chain reaction analysis and in vitro chemotaxis assays using freshly isolated DCs revealed that CCR6 was functionally expressed only by DC subsets present in the SED, while all subsets expressed functional CCR7. Moreover, none of the splenic DC subsets migrated toward MIP-3α. These data support a distinct role for MIP-3α/CCR6 in recruitment of CD11b+ DCs toward the mucosal surfaces and for MIP-3β/CCR7 in attraction of CD8α+ DCs to the T cell regions. Finally, we demonstrated that all DC subsets expressed an immature phenotype when freshly isolated and maintained expression of subset markers upon maturation in vitro. In contrast, CCR7 expression by myeloid PP DCs was enhanced with maturation in vitro. In addition, this subset disappeared from the SED and appeared in the IFR after microbial stimulation in vivo, suggesting that immature myeloid SED DCs capture antigens and migrate to IFR to initiate T cell responses after mucosal microbial infections. PMID:10770804

  8. Subsets of memory CD4+ T cell and bactericidal antibody response to Neisseria meningitidis serogroup C after immunization of HIV-infected children and adolescents.

    Directory of Open Access Journals (Sweden)

    Lucimar G Milagres

    Full Text Available Meningococcal disease is endemic in Brazil, with periodic outbreaks and case fatality rates reach as high as 18 to 20% of cases. Conjugate vaccines against meningococci are immunogenic in healthy children. However, we have previously shown a poor bactericidal antibody response to a Men C conjugate vaccine in Brazilian HIV-infected children and adolescents after a single vaccine administration. The goal of the present work was to investigate associations between bactericidal antibody response induced by MenC vaccine and the frequency and activation profile (expression of CD38, HLA-DR and CCR5 molecules of total CD4+ memory T cell sub-populations in HIV-1-infected children and adolescents. Responders to vaccination against MenC had a predominance (about 44% of CD4+ TINTERMEDIATE subset followed by TTRANSITIONAL memory subset (23 to 26%. Importantly, CD4+ TINT frequency was positively associated with bactericidal antibody response induced by vaccination. The positive correlation persisted despite the observation that the frequency TINT CD38+HLA-DR+ was higher in responders. In contrast, CD4+ TCENTRAL MEMORY (TCM subset negatively correlated with bactericidal antibodies. In conclusion, these data indicate that less differentiated CD+ T cells, like TCM may be constantly differentiating into intermediate and later differentiated CD4+ T cell subsets. These include CD4 TINT subset which showed a positive association with bactericidal antibodies.

  9. Tired telomeres: Poor global sleep quality, perceived stress, and telomere length in immune cell subsets in obese men and women.

    Science.gov (United States)

    Prather, Aric A; Gurfein, Blake; Moran, Patricia; Daubenmier, Jennifer; Acree, Michael; Bacchetti, Peter; Sinclair, Elizabeth; Lin, Jue; Blackburn, Elizabeth; Hecht, Frederick M; Epel, Elissa S

    2015-07-01

    Poor sleep quality and short sleep duration are associated with increased incidence and progression of a number of chronic health conditions observed at greater frequency among the obese and those experiencing high levels of stress. Accelerated cellular aging, as indexed by telomere attrition in immune cells, is a plausible pathway linking sleep and disease risk. Prior studies linking sleep and telomere length are mixed. One factor may be reliance on leukocytes, which are composed of varied immune cell types, as the sole measure of telomere length. To better clarify these associations, we investigated the relationships of global sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI), and diary-reported sleep duration with telomere length in different immune cell subsets, including granulocytes, peripheral blood mononuclear cells (PBMCs), CD8+ and CD4+ T lymphocytes, and B lymphocytes in a sample of 87 obese men and women (BMI mean=35.4, SD=3.6; 81.6% women; 62.8% Caucasian). Multiple linear regression analyses were performed adjusting for age, gender, race, education, BMI, sleep apnea risk, and perceived stress. Poorer PSQI global sleep quality was associated with statistically significantly shorter telomere length in lymphocytes but not granulocytes and in particular CD8+ T cells (b=-56.8 base pairs per one point increase in PSQI, SE=20.4, p=0.007) and CD4+ T cells (b=-37.2, SE=15.9, p=0.022). Among separate aspects of global sleep quality, low perceived sleep quality and decrements in daytime function were most related to shorter telomeres. In addition, perceived stress moderated the sleep-CD8+ telomere association. Poorer global sleep quality predicted shorter telomere length in CD8+ T cells among those with high perceived stress but not in low stress participants. These findings provide preliminary evidence that poorer global sleep quality is related to telomere length in several immune cell types, which may serve as a pathway linking sleep and

  10. Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans.

    Directory of Open Access Journals (Sweden)

    Fabiana Spensieri

    Full Text Available CD4+ T follicular helper cells (T(FH have been identified as the T-cell subset specialized in providing help to B cells for optimal activation and production of high affinity antibody. We recently demonstrated that the expansion of peripheral blood influenza-specific CD4(+IL-21(+ICOS1(+ T helper (T(H cells, three weeks after vaccination, associated with and predicted the rise of protective neutralizing antibodies to avian H5N1. In this study, healthy adults were vaccinated with plain seasonal trivalent inactivated influenza vaccine (TIIV, MF59(®-adjuvanted TIIV (ATIIV, or saline placebo. Frequencies of circulating CD4(+ T(FH1 ICOS(+ T(FH cells and H1N1-specific CD4(+-IL-21(+ICOS(+ CXCR5(+ T(FH and CXCR5(- T(H cell subsets were determined at various time points after vaccination and were then correlated with hemagglutination inhibition (HI titers. All three CD4(+ T cell subsets expanded in response to TIIV and ATIIV, and peaked 7 days after vaccination. To demonstrate that these T(FH cell subsets correlated with functional antibody titers, we defined an alternative endpoint metric, decorrelated HI (DHI, which removed any correlation between day 28/day 168 and day 0 HI titers, to control for the effect of preexisting immunity to influenza vaccine strains. The numbers of total circulating CD4(+T(FH1 ICOS(+ cells and of H1N1-specific CD4(+IL-21(+ICOS(+ CXCR5(+, measured at day 7, were significantly associated with day 28, and day 28 and 168 DHI titers, respectively. Altogether, our results show that CD4(+ T(FH subsets may represent valuable biomarkers of vaccine-induced long-term functional immunity.

  11. Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans

    Science.gov (United States)

    Borgogni, Erica; Zedda, Luisanna; Cantisani, Rocco; Chiappini, Nico; Schiavetti, Francesca; Rosa, Domenico; Castellino, Flora; Montomoli, Emanuele; Bodinham, Caroline L.; Lewis, David J.; Medini, Duccio; Bertholet, Sylvie; Del Giudice, Giuseppe

    2016-01-01

    CD4+ T follicular helper cells (TFH) have been identified as the T-cell subset specialized in providing help to B cells for optimal activation and production of high affinity antibody. We recently demonstrated that the expansion of peripheral blood influenza-specific CD4+IL-21+ICOS1+ T helper (TH) cells, three weeks after vaccination, associated with and predicted the rise of protective neutralizing antibodies to avian H5N1. In this study, healthy adults were vaccinated with plain seasonal trivalent inactivated influenza vaccine (TIIV), MF59®-adjuvanted TIIV (ATIIV), or saline placebo. Frequencies of circulating CD4+ TFH1 ICOS+ TFH cells and H1N1-specific CD4+IL-21+ICOS+ CXCR5+ TFH and CXCR5- TH cell subsets were determined at various time points after vaccination and were then correlated with hemagglutination inhibition (HI) titers. All three CD4+ T cell subsets expanded in response to TIIV and ATIIV, and peaked 7 days after vaccination. To demonstrate that these TFH cell subsets correlated with functional antibody titers, we defined an alternative endpoint metric, decorrelated HI (DHI), which removed any correlation between day 28/day 168 and day 0 HI titers, to control for the effect of preexisting immunity to influenza vaccine strains. The numbers of total circulating CD4+ TFH1 ICOS+ cells and of H1N1-specific CD4+IL-21+ICOS+ CXCR5+, measured at day 7, were significantly associated with day 28, and day 28 and 168 DHI titers, respectively. Altogether, our results show that CD4+ TFH subsets may represent valuable biomarkers of vaccine-induced long-term functional immunity. Trial Registration ClinicalTrials.gov NCT01771367 PMID:27336786

  12. Unbiased analysis of TCRα/β chains at the single-cell level in human CD8+ T-cell subsets.

    Directory of Open Access Journals (Sweden)

    Xiaoming Sun

    Full Text Available T-cell receptor (TCR α/β chains are expressed on the surface of CD8(+ T-cells and have been implicated in antigen recognition, activation, and proliferation. However, the methods for characterization of human TCRα/β chains have not been well established largely because of the complexity of their structures owing to the extensive genetic rearrangements that they undergo. Here we report the development of an integrated 5'-RACE and multiplex PCR method to amplify the full-length transcripts of TCRα/β at the single-cell level in human CD8(+ subsets, including naive, central memory, early effector memory, late effector memory, and effector phenotypic cells. Using this method, with an approximately 47% and 62% of PCR success rate for TCRα and for TCRβ chains, respectively, we were able to analyze more than 1,000 reads of transcripts of each TCR chain. Our comprehensive analysis revealed the following: (1 chimeric rearrangements of TCRδ-α, (2 control of TCRα/β transcription with multiple transcriptional initiation sites, (3 altered utilization of TCRα/β chains in CD8(+ subsets, and (4 strong association between the clonal size of TCRα/β chains and the effector phenotype of CD8(+ T-cells. Based on these findings, we conclude that our method is a useful tool to identify the dynamics of the TCRα/β repertoire, and provides new insights into the study of human TCRα/β chains.

  13. Unbiased analysis of TCRα/β chains at the single-cell level in human CD8+ T-cell subsets.

    Science.gov (United States)

    Sun, Xiaoming; Saito, Masumichi; Sato, Yoshinori; Chikata, Takayuki; Naruto, Takuya; Ozawa, Tatsuhiko; Kobayashi, Eiji; Kishi, Hiroyuki; Muraguchi, Atsushi; Takiguchi, Masafumi

    2012-01-01

    T-cell receptor (TCR) α/β chains are expressed on the surface of CD8(+) T-cells and have been implicated in antigen recognition, activation, and proliferation. However, the methods for characterization of human TCRα/β chains have not been well established largely because of the complexity of their structures owing to the extensive genetic rearrangements that they undergo. Here we report the development of an integrated 5'-RACE and multiplex PCR method to amplify the full-length transcripts of TCRα/β at the single-cell level in human CD8(+) subsets, including naive, central memory, early effector memory, late effector memory, and effector phenotypic cells. Using this method, with an approximately 47% and 62% of PCR success rate for TCRα and for TCRβ chains, respectively, we were able to analyze more than 1,000 reads of transcripts of each TCR chain. Our comprehensive analysis revealed the following: (1) chimeric rearrangements of TCRδ-α, (2) control of TCRα/β transcription with multiple transcriptional initiation sites, (3) altered utilization of TCRα/β chains in CD8(+) subsets, and (4) strong association between the clonal size of TCRα/β chains and the effector phenotype of CD8(+) T-cells. Based on these findings, we conclude that our method is a useful tool to identify the dynamics of the TCRα/β repertoire, and provides new insights into the study of human TCRα/β chains.

  14. Genes involved in cell division in mycoplasmas

    Directory of Open Access Journals (Sweden)

    Frank Alarcón

    2007-01-01

    Full Text Available Bacterial cell division has been studied mainly in model systems such as Escherichia coli and Bacillus subtilis, where it is described as a complex process with the participation of a group of proteins which assemble into a multiprotein complex called the septal ring. Mycoplasmas are cell wall-less bacteria presenting a reduced genome. Thus, it was important to compare their genomes to analyze putative genes involved in cell division processes. The division and cell wall (dcw cluster, which in E. coli and B. subtilis is composed of 16 and 17 genes, respectively, is represented by only three to four genes in mycoplasmas. Even the most conserved protein, FtsZ, is not present in all mycoplasma genomes analyzed so far. A model for the FtsZ protein from Mycoplasma hyopneumoniae and Mycoplasma synoviae has been constructed. The conserved residues, essential for GTP/GDP binding, are present in FtsZ from both species. A strong conservation of hydrophobic amino acid patterns is observed, and is probably necessary for the structural stability of the protein when active. M. synoviae FtsZ presents an extended amino acid sequence at the C-terminal portion of the protein, which may participate in interactions with other still unknown proteins crucial for the cell division process.

  15. Innate lymphoid cells involve in tumorigenesis.

    Science.gov (United States)

    Tian, Zhiqiang; van Velkinburgh, Jennifer C; Wu, Yuzhang; Ni, Bing

    2016-01-01

    Innate lymphoid cells (ILCs) promptly initiate cytokine responses to pathogen exposure in the mucosa and mucosal-associated lymphoid tissues. ILCs were recently categorized as being of the lymphoid lineage and have been classified into three groups. ILCs play important roles in immunity against pathogens, and an anti-tumor immune-related function was recently demonstrated. In this review we discuss whether and how ILCs involve in the tumorigenesis, providing new insights into the mechanisms underlying the particular functions of ILCs as well as the potential targets for tumor intervention.

  16. CD45/CD11b Positive Subsets of Adult Lung Anchorage-Independent Cells Harness Epithelial Stem Cells

    OpenAIRE

    2012-01-01

    Compensatory growth is mediated by multiple cell types that interact during organ repair. To elucidate the relationship between the stem/progenitor cells that proliferate or differentiate and the somatic cells of lung, we utilized a novel ex vivo pneumoexplant system. Applying this technique, we identified a sustained culture of repopulating adult progenitors in the form of free floating anchorage-independent cells (AICs). AICs did not express integrin proteins α5, β3, and β7, and constituted...

  17. Short communication: Inhibitory effects of dietary aflatoxin B1 on cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens

    Energy Technology Data Exchange (ETDEWEB)

    Liu, C.; Jiang, M.; Fang, J.; Peng, X.; Cui, H.

    2016-11-01

    Afatoxin B1 (AFB1) is the most toxic form among the mycotoxins. Cytokines are important mediators of the immune system. T-cell subsets play a crucial role in cell-mediated immunity. The aim of present study was to evaluate the effects of dietary AFB1 on the cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens throughout a 21-day experimental period. One hundred and fifty six one-day-old broiler chickens were randomly divided into control group (0 mg AFB1/kg feed) and AFB1 group (0.6 mg pure AFB1/kg feed). At 7, 14 and 21 days of age, the levels of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ and TNF-α) mRNA expression as well as the proportions of T-cell subsets (CD3+, CD3+CD4+, CD3+CD8+) by qRT-PCR and flow cytometry methods were assessed in the cecal tonsils. The levels of the seven cytokines mRNA expression and the percentages of T-cell subsets significantly decreased at 14 and 21 days of age in the AFB1 group compared with the control group. However, the CD4+/CD8+ ratio was not significantly changed. These results demonstrate that 0.6 mg/kg AFB1 dietary exposure reduced the levels of cytokines mRNA expression and the percentages of T-cell subsets in the cecal tonsils of broiler chickens, suggesting that the cell-mediated immunity of cecal tonsils might be impaired in broilers. (Author)

  18. Short communication: Inhibitory effects of dietary aflatoxin B1 on cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens

    Directory of Open Access Journals (Sweden)

    Chunyu Liu

    2016-08-01

    Full Text Available Aflatoxin B1 (AFB1 is the most toxic form among the mycotoxins. Cytokines are important mediators of the immune system. T-cell subsets play a crucial role in cell-mediated immunity. The aim of present study was to evaluate the effects of dietary AFB1 on the cytokines expression and T-cell subsets in the cecal tonsil of broiler chickens throughout a 21-day experimental period. One hundred and fifty six one-day-old broiler chickens were randomly divided into control group (0 mg AFB1/kg feed and AFB1 group (0.6 mg pure AFB1/kg feed. At 7, 14 and 21 days of age, the levels of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, IFN-γ and TNF-α mRNA expression as well as the proportions of T-cell subsets (CD3+, CD3+CD4+, CD3+CD8+ by qRT-PCR and flow cytometry methods were assessed in the cecal tonsils. The levels of the seven cytokines mRNA expression and the percentages of T-cell subsets significantly decreased at 14 and 21 days of age in the AFB1 group compared with the control group. However, the CD4+/CD8+ ratio was not significantly changed. These results demonstrate that 0.6 mg/kg AFB1 dietary exposure reduced the levels of cytokines mRNA expression and the percentages of T-cell subsets in the cecal tonsils of broiler chickens, suggesting that the cell-mediated immunity of cecal tonsils might be impaired in broilers.

  19. Dynamic changes in the numbers of different subsets of peripheral blood NK cells in patients with systemic lupus erythematosus following classic therapy.

    Science.gov (United States)

    Ma, Hongshuang; Zhao, Ling; Jiang, Zhenyu; Jiang, Yanfang; Feng, Li; Ye, Zhuang

    2014-11-01

    Imbalance of natural killer (NK) cells is associated with the development of systemic lupus erythematosus (SLE). However, little is known about the dynamic changes on NK cells following therapy. This study aimed at examining the impact of classic therapies on the numbers of different subsets of NK cells in new-onset SLE patients. The numbers of different subsets of peripheral blood NK cells in 24 new-onset SLE patients before, 4 and 12 weeks post the classic therapies, and 7 healthy controls were determined by flow cytometry. The potential correlation between the numbers of NK cells and the values of clinical measures was analyzed. In comparison with that before treatment, the numbers of NK, NKG2C+, and KIR2DL3+ NK cells were significantly increased while the numbers of NKp46+ and NKG2A + NK cells significantly decreased at 4 and/or 12 weeks post the treatment only in the drug well-responding patients, but not in those poor responders (P numbers of NKG2C + NK cells were correlated positively with the levels of serum C3 while the numbers of KIR2DL3+ NK cells were correlated negatively with the scores of SLEDAI in these patients at 4 weeks post the treatment. The classic therapies modulated the numbers of some subsets of NK cells in drug well-responding SLE patients. The changes in the numbers of some subsets of NK cells may serve as biomarkers for evaluating the therapeutic responses of SLE.

  20. Labelling of T cell subsets under field conditions in tropical countries. Adaptation of the immuno-alkaline phosphatase staining method for blood smears

    DEFF Research Database (Denmark)

    Lisse, I M; Whittle, H; Aaby, P

    1990-01-01

    Immuno-alkaline phosphatase (AP) staining for T cell subsets (CD4 and CD8) of smears from fingerprick blood functioned well under tropical climatic conditions when smears were stored frozen with silica gel before being labelled. Unlabelled smears were stored for up to 12 months and could...

  1. T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters

    DEFF Research Database (Denmark)

    Pedersen, C; Dickmeiss, E; Gaub, J;

    1990-01-01

    Seven consecutive patients who presented with a severe acute mononucleosis-like illness associated with HIV seroconversion were evaluated by T-cell subset enumerations and measurements of lymphocyte transformation responses to mitogens and antigen during both their primary illness and a 1-year...

  2. TRANSIENT AND PERMANENT ENGRAFTMENT POTENTIAL OF MURINE HEMATOPOIETIC STEM-CELL SUBSETS - DIFFERENTIAL-EFFECTS OF HOST CONDITIONING WITH GAMMA-RADIATION AND CYTOTOXIC DRUGS

    NARCIS (Netherlands)

    DOWN, JD; PLOEMACHER, RE

    1993-01-01

    Transplant of sorted donor (BG-Gpi-1(a)) hematopoietic stem cell subsets and host (BG-Gpi-1(b)) treatment with total body irradiation (TBI) or cytotoxic drugs were compared for induction of short- and long-term engraftment in a murine chimera model of congenic bone marrow transplantation (BMT). Para

  3. Identification of ITGA4/ITGB7 and ITGAE/ITGB7 expressing subsets of decidual dendritic-like cells within distinct microdomains of the pregnant mouse uterus.

    Science.gov (United States)

    Behrends, Jochen; Karsten, Christian M; Wilke, Sonja; Röbke, Astrid; Kruse, Andrea

    2008-10-01

    Several leukocyte populations have been described within the pregnant mouse uterus, some of which express the integrin beta 7 (ITGB7). Here we demonstrate that the majority of the ITGB7(+) decidual leukocytes belong to the dendritic cell (DC) lineage. By multiparameter flow cytometric analysis we demonstrated the existence of three distinct DC subsets, characterized by differential expression of ITGA4/ITGB7 (formerly alpha4beta7-integrin) and ITGAE/ITGB7 (formerly alphaEbeta7-integrin). Importantly, the predominant DC subsets reside in distinct microdomains of the Day 9 pregnant mouse uterus. ITGAX(+) ITGAM(med) ITGA4/ITGB7(+) ITGAE(-) (formerly CD11c(+) CD11b(med) alpha4beta7(+) alphaE(-)) cells represent the majority of DCs in the vascular zone (VZ), whereas ITGAX(+) ITGAM(-) ITGAE/ITGB7(+) (formerly CD11c(+) CD11b(-) alphaEbeta7(+)) DCs are mainly located in the lower central decidua basalis (cDB) and the underlying myometrium. A population of ITGAX(+) ITGAM(low) DCs lacking ITGB7 are restricted to the cDB. Confocal microscopy studies show direct contact of VZ DCs with uterine natural killer (uNK) cells, suggesting a functional relationship between both cell populations. Collectively, our data identify three phenotypically distinct DC subsets residing in distinct microdomains of the uterus. The differential expression of ITGA4/ITGB7 and ITGAE/ITGB7 suggests distinct functional roles of the different DC subsets during early pregnancy.

  4. A Single Subset of Dendritic Cells Controls the Cytokine Bias of Natural Killer T Cell Responses to Diverse Glycolipid Antigens

    Science.gov (United States)

    Arora, Pooja; Baena, Andres; Yu, Karl O.A.; Saini, Neeraj K.; Kharkwal, Shalu S.; Goldberg, Michael F.; Kunnath-Velayudhan, Shajo; Carreño, Leandro J.; Venkataswamy, Manjunatha M.; Kim, John; Lazar-Molnar, Eszter; Lauvau, Gregoire; Chang, Young-tae; Liu, Zheng; Bittman, Robert; Al-Shamkhani, Aymen; Cox, Liam R.; Jervis, Peter J.; Veerapen, Natacha; Besra, Gurdyal S.; Porcelli, Steven A.

    2014-01-01

    Summary Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α+ DEC-205+ dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α+ dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses. PMID:24412610

  5. A single subset of dendritic cells controls the cytokine bias of natural killer T cell responses to diverse glycolipid antigens.

    Science.gov (United States)

    Arora, Pooja; Baena, Andres; Yu, Karl O A; Saini, Neeraj K; Kharkwal, Shalu S; Goldberg, Michael F; Kunnath-Velayudhan, Shajo; Carreño, Leandro J; Venkataswamy, Manjunatha M; Kim, John; Lazar-Molnar, Eszter; Lauvau, Gregoire; Chang, Young-tae; Liu, Zheng; Bittman, Robert; Al-Shamkhani, Aymen; Cox, Liam R; Jervis, Peter J; Veerapen, Natacha; Besra, Gurdyal S; Porcelli, Steven A

    2014-01-16

    Many hematopoietic cell types express CD1d and are capable of presenting glycolipid antigens to invariant natural killer T cells (iNKT cells). However, the question of which cells are the principal presenters of glycolipid antigens in vivo remains controversial, and it has been suggested that this might vary depending on the structure of a particular glycolipid antigen. Here we have shown that a single type of cell, the CD8α(+) DEC-205(+) dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. After glycolipid presentation, these dendritic cells rapidly altered their expression of various costimulatory and coinhibitory molecules in a manner that was dependent on the structure of the antigen. These findings show flexibility in the outcome of two-way communication between CD8α(+) dendritic cells and iNKT cells, providing a mechanism for biasing toward either proinflammatory or anti-inflammatory responses.

  6. Cellular and molecular characterization of multipolar Map5-expressing cells: a subset of newly generated, stage-specific parenchymal cells in the mammalian central nervous system.

    Science.gov (United States)

    Crociara, Paola; Parolisi, Roberta; Conte, Daniele; Fumagalli, Marta; Bonfanti, Luca

    2013-01-01

    Although extremely interesting in adult neuro-glio-genesis and promising as an endogenous source for repair, parenchymal progenitors remain largely obscure in their identity and physiology, due to a scarce availability of stage-specific markers. What appears difficult is the distinction between real cell populations and various differentiation stages of the same population. Here we focused on a subset of multipolar, polydendrocyte-like cells (mMap5 cells) expressing the microtubule associated protein 5 (Map5), which is known to be present in most neurons. We characterized the morphology, phenotype, regional distribution, proliferative dynamics, and stage-specific marker expression of these cells in the rabbit and mouse CNS, also assessing their existence in other mammalian species. mMap5 cells were never found to co-express the Ng2 antigen. They appear to be a population of glial cells sharing features but also differences with Ng2+progenitor cells. We show that mMap5 cells are newly generated, postmitotic parenchymal elements of the oligodendroglial lineage, thus being a stage-specific population of polydendrocytes. Finally, we report that the number of mMap5 cells, although reduced within the brain of adult/old animals, can increase in neurodegenerative and traumatic conditions.

  7. Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease.

    Directory of Open Access Journals (Sweden)

    Franklin R Toapanta

    2016-06-01

    Full Text Available A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD- 6-9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h and/or microbiological (S. Typhi bacteremia endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD- was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml of TD volunteers during disease days and increase in plasmablasts (PB during the recovery phase (>day 14. Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21 and gut homing (integrin α4β7 molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans.

  8. Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease

    Science.gov (United States)

    Toapanta, Franklin R.; Bernal, Paula J.; Fresnay, Stephanie; Magder, Laurence S.; Darton, Thomas C.; Jones, Claire; Waddington, Claire S.; Blohmke, Christoph J.; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.; Sztein, Marcelo B.

    2016-01-01

    A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD-) 6–9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h) and/or microbiological (S. Typhi bacteremia) endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD-) was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml) of TD volunteers during disease days and increase in plasmablasts (PB) during the recovery phase (>day 14). Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21) and gut homing (integrin α4β7) molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm) CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um) and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD) volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans. PMID:27300136

  9. Oral Challenge with Wild-Type Salmonella Typhi Induces Distinct Changes in B Cell Subsets in Individuals Who Develop Typhoid Disease.

    Science.gov (United States)

    Toapanta, Franklin R; Bernal, Paula J; Fresnay, Stephanie; Magder, Laurence S; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

    2016-06-01

    A novel human oral challenge model with wild-type Salmonella Typhi (S. Typhi) was recently established by the Oxford Vaccine Group. In this model, 104 CFU of Salmonella resulted in 65% of participants developing typhoid fever (referred here as typhoid diagnosis -TD-) 6-9 days post-challenge. TD was diagnosed in participants meeting clinical (oral temperature ≥38°C for ≥12h) and/or microbiological (S. Typhi bacteremia) endpoints. Changes in B cell subpopulations following S. Typhi challenge remain undefined. To address this issue, a subset of volunteers (6 TD and 4 who did not develop TD -NoTD-) was evaluated. Notable changes included reduction in the frequency of B cells (cells/ml) of TD volunteers during disease days and increase in plasmablasts (PB) during the recovery phase (>day 14). Additionally, a portion of PB of TD volunteers showed a significant increase in activation (CD40, CD21) and gut homing (integrin α4β7) molecules. Furthermore, all BM subsets of TD volunteers showed changes induced by S. Typhi infections such as a decrease in CD21 in switched memory (Sm) CD27+ and Sm CD27- cells as well as upregulation of CD40 in unswitched memory (Um) and Naïve cells. Furthermore, changes in the signaling profile of some BM subsets were identified after S. Typhi-LPS stimulation around time of disease. Notably, naïve cells of TD (compared to NoTD) volunteers showed a higher percentage of cells phosphorylating Akt suggesting enhanced survival of these cells. Interestingly, most these changes were temporally associated with disease onset. This is the first study to describe differences in B cell subsets directly related to clinical outcome following oral challenge with wild-type S. Typhi in humans.

  10. Evidences Suggesting Involvement of Viruses in Oral Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Kanupriya Gupta

    2013-01-01

    Full Text Available Oral cancer is one of the most common cancers and it constitutes a major health problem particularly in developing countries. Oral squamous cell carcinoma (OSCC represents the most frequent of all oral neoplasms. Several risk factors have been well characterized to be associated with OSCC with substantial evidences. The etiology of OSCC is complex and involves many factors. The most clearly defined potential factors are smoking and alcohol, which substantially increase the risk of OSCC. However, despite this clear association, a substantial proportion of patients develop OSCC without exposure to them, emphasizing the role of other risk factors such as genetic susceptibility and oncogenic viruses. Some viruses are strongly associated with OSCC while the association of others is less frequent and may depend on cofactors for their carcinogenic effects. Therefore, the exact role of viruses must be evaluated with care in order to improve the diagnosis and treatment of OSCC. Although a viral association within a subset of OSCC has been shown, the molecular and histopathological characteristics of these tumors have yet to be clearly defined.

  11. Increased tubulointerstitial recruitment of human CD141(hi) CLEC9A(+) and CD1c(+) myeloid dendritic cell subsets in renal fibrosis and chronic kidney disease.

    Science.gov (United States)

    Kassianos, Andrew J; Wang, Xiangju; Sampangi, Sandeep; Muczynski, Kimberly; Healy, Helen; Wilkinson, Ray

    2013-11-15

    Dendritic cells (DCs) play critical roles in immune-mediated kidney diseases. Little is known, however, about DC subsets in human chronic kidney disease, with previous studies restricted to a limited set of pathologies and to using immunohistochemical methods. In this study, we developed novel protocols for extracting renal DC subsets from diseased human kidneys and identified, enumerated, and phenotyped them by multicolor flow cytometry. We detected significantly greater numbers of total DCs as well as CD141(hi) and CD1c(+) myeloid DC (mDCs) subsets in diseased biopsies with interstitial fibrosis than diseased biopsies without fibrosis or healthy kidney tissue. In contrast, plasmacytoid DC numbers were significantly higher in the fibrotic group compared with healthy tissue only. Numbers of all DC subsets correlated with loss of kidney function, recorded as estimated glomerular filtration rate. CD141(hi) DCs expressed C-type lectin domain family 9 member A (CLEC9A), whereas the majority of CD1c(+) DCs lacked the expression of CD1a and DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), suggesting these mDC subsets may be circulating CD141(hi) and CD1c(+) blood DCs infiltrating kidney tissue. Our analysis revealed CLEC9A(+) and CD1c(+) cells were restricted to the tubulointerstitium. Notably, DC expression of the costimulatory and maturation molecule CD86 was significantly increased in both diseased cohorts compared with healthy tissue. Transforming growth factor-β levels in dissociated tissue supernatants were significantly elevated in diseased biopsies with fibrosis compared with nonfibrotic biopsies, with mDCs identified as a major source of this profibrotic cytokine. Collectively, our data indicate that activated mDC subsets, likely recruited into the tubulointerstitium, are positioned to play a role in the development of fibrosis and, thus, progression to chronic kidney disease.

  12. The Transcription Factor AHR Prevents the Differentiation of a Stage 3 Innate Lymphoid Cell Subset to Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Tiffany Hughes

    2014-07-01

    Full Text Available Accumulating evidence indicates that human natural killer (NK cells develop in secondary lymphoid tissue (SLT through a so-called “stage 3” developmental intermediate minimally characterized by a CD34−CD117+CD94− immunophenotype that lacks mature NK cell function. This stage 3 population is heterogeneous, potentially composed of functionally distinct innate lymphoid cell (ILC types that include interleukin-1 receptor (IL-1R1-positive, IL-22-producing ILC3s. Whether human ILC3s are developmentally related to NK cells is a subject of ongoing investigation. Here, we show that antagonism of the aryl hydrocarbon receptor (AHR or silencing of AHR gene expression promotes the differentiation of tonsillar IL-22-producing IL-1R1hi human ILC3s to CD56brightCD94+ interferon (IFN-γ-producing cytolytic mature NK cells expressing eomesodermin (EOMES and T-Box Protein 21 (TBX21 or TBET. Hence, we demonstrate the lineage plasticity of human ILCs by identifying AHR as a transcription factor that prevents IL-1R1hi ILC3s from differentiating into NK cells.

  13. The magnitude of HIV-1 resistance to the CCR5 antagonist maraviroc may impart a differential alteration in HIV-1 tropism for macrophages and T-cell subsets.

    Science.gov (United States)

    Flynn, Jacqueline K; Paukovics, Geza; Moore, Miranda S; Ellett, Anne; Gray, Lachlan R; Duncan, Renee; Salimi, Hamid; Jubb, Becky; Westby, Mike; Purcell, Damian F J; Lewin, Sharon R; Lee, Benhur; Churchill, Melissa J; Gorry, Paul R; Roche, Michael

    2013-07-20

    Human immunodeficiency virus type 1 (HIV-1) resistance to CCR5 antagonists, including maraviroc (MVC), results from alterations in the HIV-1 envelope glycoproteins (Env) enabling recognition of antagonist-bound CCR5. Here, we characterized tropism alterations for CD4+ T-cell subsets and macrophages by Envs from two subjects who developed MVC resistance in vivo, which displayed either relatively efficient or inefficient recognition of MVC-bound CCR5. We show that MVC-resistant Env with efficient recognition of drug-bound CCR5 displays a tropism shift for CD4+ T-cell subsets associated with increased infection of central memory T-cells and reduced infection of effector memory and transitional memory T-cells, and no change in macrophage infectivity. In contrast, MVC-resistant Env with inefficient recognition of drug-bound CCR5 displays no change in tropism for CD4+ T-cell subsets, but exhibits a significant reduction in macrophage infectivity. The pattern of HIV-1 tropism alterations for susceptible cells may therefore be variable in subjects with MVC resistance.

  14. DeepSNVMiner: a sequence analysis tool to detect emergent, rare mutations in subsets of cell populations

    Directory of Open Access Journals (Sweden)

    T. Daniel Andrews

    2016-05-01

    Full Text Available Background. Massively parallel sequencing technology is being used to sequence highly diverse populations of DNA such as that derived from heterogeneous cell mixtures containing both wild-type and disease-related states. At the core of such molecule tagging techniques is the tagging and identification of sequence reads derived from individual input DNA molecules, which must be first computationally disambiguated to generate read groups sharing common sequence tags, with each read group representing a single input DNA molecule. This disambiguation typically generates huge numbers of reads groups, each of which requires additional variant detection analysis steps to be run specific to each read group, thus representing a significant computational challenge. While sequencing technologies for producing these data are approaching maturity, the lack of available computational tools for analysing such heterogeneous sequence data represents an obstacle to the widespread adoption of this technology. Results. Using synthetic data we successfully detect unique variants at dilution levels of 1 in a 1,000,000 molecules, and find DeeepSNVMiner obtains significantly lower false positive and false negative rates compared to popular variant callers GATK, SAMTools, FreeBayes and LoFreq, particularly as the variant concentration levels decrease. In a dilution series with genomic DNA from two cells lines, we find DeepSNVMiner identifies a known somatic variant when present at concentrations of only 1 in 1,000 molecules in the input material, the lowest concentration amongst all variant callers tested. Conclusions. Here we present DeepSNVMiner; a tool to disambiguate tagged sequence groups and robustly identify sequence variants specific to subsets of starting DNA molecules that may indicate the presence of a disease. DeepSNVMiner is an automated workflow of custom sequence analysis utilities and open source tools able to differentiate somatic DNA variants from

  15. Latency-associated peptide identifies a novel CD4+CD25+ regulatory T cell subset with TGFbeta-mediated function and enhanced suppression of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Chen, Mei-Ling; Yan, Bo-Shiun; Bando, Yoshio; Kuchroo, Vijay K; Weiner, Howard L

    2008-06-01

    CD4(+)CD25(+) regulatory T cells (Tregs) are essential for maintaining self-tolerance and immune homeostasis. Here we characterize a novel subset of CD4(+)CD25(+) Tregs that express latency-associated peptide (LAP) on their cell surface (CD4(+)CD25(+)LAP(+) cells). CD4(+)CD25(+)LAP(+) cells express elevated levels of Foxp3 and Treg-associated molecules (CTLA4, glucocorticoid-induced TNFR-related gene), secrete TGFbeta, and express both cell surface TGFbeta and surface receptors for TGFbeta. In vitro, the suppressive function of CD4(+)CD25(+)LAP(+) cells is both cell contact and soluble factor dependent; this contrasts with CD4(+)CD25(+)LAP(-) cells, which are mainly cell contact dependent. In a model of experimental autoimmune encephalomyelitis, CD4(+)CD25(+)LAP(+) cells exhibit more potent suppressive activity than CD4(+)CD25(+)LAP(-) cells, and the suppression is TGFbeta dependent. We further show that CD4(+)CD25(+)LAP(+) cells suppress myelin oligodendrocyte glycoprotein-specific immune responses by inducing Foxp3 and by inhibiting IL-17 production. Our findings demonstrate that CD4(+)CD25(+) Tregs are a heterogeneous population and that the CD4(+)CD25(+) subset that expresses LAP functions in a TGFbeta-dependent manner and has greater in vivo suppressive properties. Our work helps elucidate the ambiguity concerning the role of TGFbeta in CD4(+)CD25(+) Treg-mediated suppression and indicates that LAP is an authentic marker able to identify a TGFbeta-expressing CD4(+)CD25(+) Treg subset.

  16. Stress-Induced In Vivo Recruitment of Human Cytotoxic Natural Killer Cells Favors Subsets with Distinct Receptor Profiles and Associates with Increased Epinephrine Levels.

    Directory of Open Access Journals (Sweden)

    Marc B Bigler

    Full Text Available Acute stress drives a 'high-alert' response in the immune system. Psychoactive drugs induce distinct stress hormone profiles, offering a sought-after opportunity to dissect the in vivo immunological effects of acute stress in humans.3,4-methylenedioxymethamphetamine (MDMA, methylphenidate (MPH, or both, were administered to healthy volunteers in a randomized, double-blind, placebo-controlled crossover-study. Lymphocyte subset frequencies, natural killer (NK cell immune-phenotypes, and changes in effector function were assessed, and linked to stress hormone levels and expression of CD62L, CX3CR1, CD18, and stress hormone receptors on NK cells.MDMA/MPH > MDMA > MPH robustly induced an epinephrine-dominant stress response. Immunologically, rapid redistribution of peripheral blood lymphocyte-subsets towards phenotypically mature NK cells occurred. NK cytotoxicity was unaltered, but they expressed slightly reduced levels of the activating receptor NKG2D. Preferential circulation of mature NK cells was associated with high epinephrine receptor expression among this subset, as well as expression of integrin ligands previously linked to epinephrine-induced endothelial detachment.The acute epinephrine-induced stress response was characterized by rapid accumulation of mature and functional NK cells in the peripheral circulation. This is in line with studies using other acute stressors and supports the role of the acute stress response in rapidly mobilizing the innate immune system to counteract incoming threats.

  17. Ion Channels Involved in Cell Volume Regulation

    DEFF Research Database (Denmark)

    Hoffmann, Else Kay

    2011-01-01

    This mini review outlines studies of cell volume regulation in two closely related mammalian cell lines: nonadherent Ehrlich ascites tumour cells (EATC) and adherent Ehrlich Lettre ascites (ELA) cells. Focus is on the regulatory volume decrease (RVD) that occurs after cell swelling, the volume...

  18. Cranial involvement in sickle cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Alkan, Ozlem, E-mail: yalinozlem@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kizilkilic, Ebru, E-mail: ebru90@yahoo.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kizilkilic, Osman, E-mail: ebos90@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Yildirim, Tulin, E-mail: ytulin@hotmail.com [Department of Radiology, Faculty of Medicine, Baskent University, Ankara (Turkey); Karaca, Sibel, E-mail: sibelkaraca@hotmail.com [Department of Neurology, Faculty of Medicine, Baskent University, Ankara (Turkey); Yeral, Mahmut, E-mail: mahmutyeral@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Kasar, Mutlu, E-mail: mutlukasar@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey); Ozdogu, Hakan, E-mail: hakanozdogu@hotmail.com [Department of Hematology, Faculty of Medicine, Baskent University, Ankara (Turkey)

    2010-11-15

    Purpose: To evaluate cranial findings in patients with neurologically symptomatic sickle cell disease (SCD). Materials and methods: We studied 50 consecutive patients with SCD and neurologic symptoms. All patients underwent brain MR examinations: all 50 underwent classic MR imaging; 42, diffusion-weighted MR imaging; 10, MR angiography; four, MR venography; and three patients, digital subtraction angiography. Results: Of the 50 SCD patients, 19 (38%) had normal MR findings, and 31 (62%) showed abnormalities on brain MR images. Of the 50 patients, 16 (32%) had ischemic lesions; two (4%), subarachnoid hemorrhage; one (2%), moya-moya pattern; one (2%), posterior reversible encephalopathy; one (2%), dural venous sinus thrombosis; 12 (24%), low marrow signal intensity and thickness of the diploic space; 12 (24%), cerebral atrophy; and two (4%), osteomyelitis. Twenty-seven patients (54%) presented with headache, which was the most common clinical finding. Conclusions: The cranial involvement is one of the most devastating complications of SCD. Early and accurate diagnosis is important in the management of cranial complications of SCD.

  19. Effect of plasma viremia on apoptosis and immunophenotype of dendritic cells subsets in acute SIVmac239 infection of Chinese rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Hou-Jun Xia

    Full Text Available Non-human primates such as Chinese rhesus macaques (Ch Rhs provide good animal models for research on human infectious diseases. Similar to humans, there are two principal subsets of dendritic cells (DCs in the peripheral blood of Ch Rhs: myeloid DCs (mDCs and plasmacytoid DCs (pDCs. In this study, two-color fluorescence-activated cell sorting (FACS analyses were used to identify the main DC subsets, namely CD1c(+ mDCs and pDCs from Ch Rhs. Then, the apoptosis and immunophenotype changes of DCs subsets were first described during the acute phase of SIVmac239 infection. Both the DCs subsets showed decreased CD4 expression and enhanced CCR5 expression; in particular, those of pDCs significantly changed at most time points. Interestingly, the plasma viral loads were negatively correlated with CD4 expression, but were positively correlated with CCR5 expression of pDCs. During this period, both CD1c(+ mDCs and pDCs were activated by enhancing expressions of co-stimulatory molecules, accompanied with increase in CCR7. Either CD80 or CD86 expressed on CD1c(+ mDCs and pDCs was positively correlated with the plasma viral loads. Our analysis demonstrates that the pDCs were more prone to apoptosis after infection during the acute phase of SIVmac239 infection, which may be due to their high expressions of CD4 and CCR5. Both DCs subsets activated through elevating the expression of co-stimulatory molecules, which was beneficial in controlling the replication of SIV. However, a mere broad immune activation initiated by activated DCs may lead to tragic AIDS progression.

  20. The cancer-testis antigen NY-ESO-1 is highly expressed in myxoid and round cell subset of liposarcomas.

    Science.gov (United States)

    Hemminger, Jessica A; Ewart Toland, Amanda; Scharschmidt, Thomas J; Mayerson, Joel L; Kraybill, William G; Guttridge, Denis C; Iwenofu, O Hans

    2013-02-01

    Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n=15): myxoid and round cell (n=8); well-differentiated (n=4), and dedifferentiated (n=3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n=44): myxoid and round cell (n=18); well-differentiated (n=10); dedifferentiated (n=10); and pleomorphic (n=6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1-3+), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2-3+ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1+ intensity in 50% of cells; 2+ intensity in 5% of cells; and 3+ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3+ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this

  1. [Helper T cell paradigm: Th17 and regulatory T cells involved in autoimmune inflammatory disorders, pathogen defense and allergic diseases].

    Science.gov (United States)

    Noma, Takeshi

    2010-01-01

    The helper T cell paradigm, divided into two distinct subsets, Th1 and Th2 cells, characterized by distinct cytokine and functions, has been expanded to IL-17-producing Th17 cells. Th1 cells producing IFN-γ are involved in delayed-type hypersensitivity, effective in intracellular pathogens defense, while Th2 cells secrete IL-4, IL-5, IL-13 and IL-25 and has a central role in IgE production, eosinophilic inflammation, and the protection for helminthic parasite infection. Th17 cell lineages, expressing IL-17 family of cytokines and IL-23-mediated functions on T cells, plays a role in immune response to fungi and extracellular pathogens and autoimmune inflammatory disorders. Th17 cells are required the combination of IL-6 and TGF-β and the transcription factors, RORC2/RORgt (mice) and STAT3 for differentiation, and produce IL-17, IL-22, IL-17F, IL-21 and CCL20. FOXP3+ regulatory T (Treg) cells produce TGF-β and IL-10, which regulate effector T cells, and thus maintain peripheral tolerance. Four functionally unique CD4+ T cells, including the regulatory T (Treg) cells are now involved in the regulation of immune responses to pathogens, self-antigens and allergens. Any defect in the entire CD4+T cell population might results in human diseases. In this review, the biology of Th17 cells and Treg cells and their role in immune diseases are presented.

  2. Signaling involved in stem cell reprogramming and differentiation

    Institute of Scientific and Technical Information of China (English)

    Shihori; Tanabe

    2015-01-01

    Stem cell differentiation is regulated by multiple signaling events. Recent technical advances have reve-aled that differentiated cells can be reprogrammed into stem cells. The signals involved in stem cell pro-gramming are of major interest in stem cell research. The signaling mechanisms involved in regulating stem cell reprogramming and differentiation are the subject of intense study in the field of life sciences. In this review,the molecular interactions and signaling pathways related to stem cell differentiation are discussed.

  3. [The impact of donor naive and memory T cell subsets on patient outcome following allogeneic stem cell transplantation: relationship between infused donor CD4+/CCR7+ T cell subsets and acute graft-versus-host disease].

    Science.gov (United States)

    Choufi, B; Thiant, S; Trauet, J; Cliquennois, M; Cherrel, M; Boulanger, F; Coiteux, V; Magro, L; Labalette, M; Yakoub-Agha, I

    2014-06-01

    In a previous prospective study on 62 patients who underwent an HLA-matched allogeneic stem cell transplantation, we have observed that proportion of donor-derived CCR7(+)/CD4(+) T cells in the graft provided a predictive indicator of acute GVHD without interfering on chronic GVHD and relapse rate. Here we present our results on a confirmatory cohort of 137 consecutive patients. Indeed patients who received more than 76% of CCR7(+)/CD4(+) T cells in the graft developed more often acute GVHD be it of low or high grade than those who did not. Determination of the CCR7(+)/CCR7(neg) ratio of CD4(+) T cells in the graft provides a predictive indicator of acute GVHD and could help to define strategies of partial selective T cell depleted transplantation.

  4. Cortisol increases CXCR4 expression but does not affect CD62L and CCR7 levels on specific T cell subsets in humans.

    Science.gov (United States)

    Besedovsky, Luciana; Linz, Barbara; Dimitrov, Stoyan; Groch, Sabine; Born, Jan; Lange, Tanja

    2014-06-01

    Glucocorticoids are well known to affect T cell migration, leading to a redistribution of the cells from blood to the bone marrow, accompanied by a concurrent suppression of lymph node homing. Despite numerous studies in this context, with most of them employing synthetic glucocorticoids in nonphysiological doses, the mechanisms of this redistribution are not well understood. Here, we investigated in healthy men the impact of cortisol at physiological concentrations on the expression of different migration molecules on eight T cell subpopulations in vivo and in vitro. Hydrocortisone (cortisol, 22 mg) infused during nocturnal rest when endogenous cortisol levels are low, compared with placebo, differentially reduced numbers of T cell subsets, with naive CD4(+) and CD8(+) subsets exhibiting the strongest reduction. Hydrocortisone in vivo and in vitro increased CXCR4 expression, which presumably mediates the recruitment of T cells to the bone marrow. Expression of the lymph node homing receptor CD62L on total CD3(+) and CD8(+) T cells appeared reduced following hydrocortisone infusion. However, this was due to a selective extravasation of CD62L(+) T cell subsets, as hydrocortisone affected neither CD62L expression on a subpopulation level nor CD62L expression in vitro. Corresponding results in the opposite direction were observed after blocking of endogenous cortisol synthesis by metyrapone. CCR7, another lymph node homing receptor, was also unaffected by hydrocortisone in vitro. Thus, cortisol seems to redirect T cells to the bone marrow by upregulating their CXCR4 expression, whereas its inhibiting effect on T cell homing to lymph nodes is apparently regulated independently of the expression of classical homing receptors.

  5. TCR sequences and tissue distribution discriminate the subsets of naïve and activated/memory Treg cells in mice.

    Science.gov (United States)

    Bergot, Anne-Sophie; Chaara, Wahiba; Ruggiero, Eliana; Mariotti-Ferrandiz, Encarnita; Dulauroy, Sophie; Schmidt, Manfred; von Kalle, Christof; Six, Adrien; Klatzmann, David

    2015-05-01

    Analyses of the regulatory T (Treg) cell TCR repertoire should help elucidate the nature and diversity of their cognate antigens and thus how Treg cells protect us from autoimmune diseases. We earlier identified CD44(hi) CD62L(low) activated/memory (am) Treg cells as a Treg-cell subset with a high turnover and possible self-specificity. We now report that amTreg cells are predominantly distributed in lymph nodes (LNs) draining deep tissues. Multivariate analyses of CDR3 spectratyping first revealed that amTreg TCR repertoire is different from that of naïve Treg cells (nTreg cells) and effector T (Teff) cells. Furthermore, in deep- versus superficial LNs, TCR-β deep sequencing further revealed diversified nTreg-cell and amTreg-cell repertoires, although twofold less diverse than that of Teff cells, and with repertoire richness significantly lower in deep-LN versus superficial-LN Treg cells. Importantly, expanded clonotypes were mostly detected in deep-LN amTreg cells, some accounting for 20% of the repertoire. Strikingly, these clonotypes were absent from nTreg cells, but found at low frequency in Teff cells. Our results, obtained in nonmanipulated mice, indicate different antigenic targets for naïve and amTreg cells and that amTreg cells are self-specific. The data we present are consistent with an instructive component in Treg-cell differentiation.

  6. Depletion of Regulatory T Cells Induces High Numbers of Dendritic Cells and Unmasks a Subset of Anti-Tumour CD8+CD11c+ PD-1lo Effector T Cells.

    Directory of Open Access Journals (Sweden)

    Nicolas Goudin

    Full Text Available Natural regulatory T (Treg cells interfere with multiple functions, which are crucial for the development of strong anti-tumour responses. In a model of 4T1 mammary carcinoma, depletion of CD25+Tregs results in tumour regression in Balb/c mice, but the mechanisms underlying this process are not fully understood. Here, we show that partial Treg depletion leads to the generation of a particular effector CD8 T cell subset expressing CD11c and low level of PD-1 in tumour draining lymph nodes. These cells have the capacity to migrate into the tumour, to kill DCs, and to locally regulate the anti-tumour response. These events are concordant with a substantial increase in CD11b+ resident dendritic cells (DCs subsets in draining lymph nodes followed by CD8+ DCs. These results indicate that Treg depletion leads to tumour regression by unmasking an increase of DC subsets as a part of a program that optimizes the microenvironment by orchestrating the activation, amplification, and migration of high numbers of fully differentiated CD8+CD11c+PD1lo effector T cells to the tumour sites. They also indicate that a critical pattern of DC subsets correlates with the evolution of the anti-tumour response and provide a template for Treg depletion and DC-based therapy.

  7. LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

    Science.gov (United States)

    Islas-Vazquez, Lorenzo; Prado-Garcia, Heriberto; Aguilar-Cazares, Dolores; Meneses-Flores, Manuel; Galicia-Velasco, Miriam; Romero-Garcia, Susana; Camacho-Mendoza, Catalina; Lopez-Gonzalez, Jose Sullivan

    2015-01-01

    Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP) TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells. PMID:26582240

  8. LAP TGF-Beta Subset of CD4+CD25+CD127− Treg Cells is Increased and Overexpresses LAP TGF-Beta in Lung Adenocarcinoma Patients

    Directory of Open Access Journals (Sweden)

    Lorenzo Islas-Vazquez

    2015-01-01

    Full Text Available Lung cancer is the leading cause of cancer death worldwide. Adenocarcinoma, the most commonly diagnosed histologic type of lung cancer, is associated with smoking. Cigarette smoke promotes inflammation on the airways, which might be mediated by Th17 cells. This inflammatory environment may contribute to tumor development. In contrast, some reports indicate that tumors may induce immunosuppressive Treg cells to dampen immune reactivity, supporting tumor growth and progression. Thus, we aimed to analyze whether chronic inflammation or immunosuppression predominates at the systemic level in lung adenocarcinoma patients, and several cytokines and Th17 and Treg cells were studied. Higher proportions of IL-17-producing CD4+ T-cells were found in smoking control subjects and in lung adenocarcinoma patients compared to nonsmoking control subjects. In addition, lung adenocarcinoma patients increased both plasma concentrations of IL-2, IL-4, IL-6, and IL-10, and proportions of Latency Associated Peptide (LAP TGF-β subset of CD4+CD25+CD127− Treg cells, which overexpressed LAP TGF-β. This knowledge may lead to the development of immunotherapies that could inhibit the suppressor activity mediated by the LAP TGF-β subset of CD4+CD25+CD127− Treg cells to promote reactivity of immune cells against lung adenocarcinoma cells.

  9. Shortened telomere length is demonstrated in T-cell subsets together with a pronounced increased telomerase activity in CD4 positive T cells from blood of patients with mycosis fungoides and parapsoriasis.

    Science.gov (United States)

    Wu, K D; Hansen, E R

    2001-10-01

    We have recently demonstrated that telomerase activity is increased and telomere length shortened in lymphocytes from peripheral blood of patients with cutaneous T-cell lymphoma. In order to determine which cell type has increased telomerase activity and shortened telomere length, CD4+, CD8+, CLA+ CD3+ and CLA- CD3+ T cells were isolated from peripheral blood of 25 patients, including 15 patients with mycosis fungoides and 10 patients with parapsoriasis. Eleven healthy individuals were used as controls; CD19+ B cells were separated from each individual as an internal control. The results showed that the increased telomerase activity was significantly predominating in the CD4+ T-cell subset. Significantly shortened telomere length was found in CD4+ and CD8+ T-cell subsets from the patients compared with the same cell subsets obtained from healthy individuals. However, no difference was observed between the subsets; CD19+ B cells collected from patients and healthy control individuals had similar telomerase activity and telomere length which was significantly different from the values found in T cells. The telomere length was significantly shorter in CLA+ CD3+ subset than in CLA- CD3+ subset. Interestingly, increased telomerase activity and shortened telomere length was also detected in CD4+ T cells from patients with parapsoriasis indicating that alteration of telomerase activity and telomere length in CD4+ T cells is an early event in the pathogenesis of cutaneous T-cell lymphoma. Thus, the results indicate that a significant high level of telomerase activity and shortened telomere length frequently occur in T cells of patients with CTCL and may reflect tumorigenesis.

  10. T cells and T-cell subsets in mycosis fungoides and parapsoriasis. A study of 18 cases with anti-human T-cell monoclonal antibodies and histochemical techniques.

    Science.gov (United States)

    Buechner, S A; Winkelmann, R K; Banks, P M

    1984-07-01

    Skin lesions from 15 patients with mycosis fungoides (MF) and from three with parapsoriasis were studied immunohistochemically with monoclonal antibodies against T cells (Leu 1) and against T-cell subsets (Leu 2a, Leu 3a). Lymphoid cell reactivity was diverse among these sampled cases. In two cases of parapsoriasis and nine of MF, there was a predominance of helper/inducer (Leu-3a-reactive) cells over suppressor/cytotoxic (Leu-2a-reactive) cells. In one case of parapsoriasis and one (advanced tumor stage) of MF, there was suppressor/cytotoxic cell predominance. One case of MF showed strong reactivity for both T-cell subset markers. Four cases of MF (two plaque-stage and two tumor-stage) featured a predominant cell type in the dermis which was nonreactive for all three antibodies. The intraepidermal lymphoid cellularity was Leu-1-reactive in ten cases of MF and two of parapsoriasis. Among these 12 cases, the intraepidermal cellularity was Leu-2a-reactive in four and Leu-3a-reactive in three. The use of such studies of T-cell subsets on in situ cutaneous lymphoid infiltrates may demonstrate a correlation with cytomorphology, clinical stage, and disease prognosis.

  11. N-acetylcysteine increases the frequency of bone marrow pro-B/pre-B cells, but does not reverse cigarette smoking-induced loss of this subset.

    Directory of Open Access Journals (Sweden)

    Victoria L Palmer

    Full Text Available BACKGROUND: We previously showed that mice exposed to cigarette smoke for three weeks exhibit loss of bone marrow B cells at the Pro-B-to-pre-B cell transition, but the reason for this is unclear. The antioxidant N-acetylcysteine (NAC, a glutathione precursor, has been used as a chemopreventive agent to reduce adverse effects of cigarette smoke exposure on lung function. Here we determined whether smoke exposure impairs B cell development by inducing cell cycle arrest or apoptosis, and whether NAC treatment prevents smoking-induced loss of developing B cells. METHODOLOGY/PRINCIPAL FINDINGS: Groups of normal mice were either exposed to filtered room air or cigarette smoke with or without concomitant NAC treatment for 5 days/week for three weeks. Bone marrow B cell developmental subsets were enumerated, and sorted pro-B (B220(+CD43(+ and pre-B (B220(+CD43(- cell fractions were analyzed for cell cycle status and the percentage of apoptotic cells. We find that, compared to sham controls, smoke-exposed mice have ∼60% fewer pro-B/pre-B cells, regardless of NAC treatment. Interestingly, NAC-treated mice show a 21-38% increase in total bone marrow cellularity and lymphocyte frequency and about a 2-fold increase in the pro-B/pre-B cell subset, compared to sham-treated controls. No significant smoking- or NAC-dependent differences were detected in frequency of apoptotic cells or the percentage cells in the G1, S, or G2 phases of the cycle. CONCLUSIONS/SIGNIFICANCE: The failure of NAC treatment to prevent smoking-induced loss of bone marrow pre-B cells suggests that oxidative stress is not directly responsible for this loss. The unexpected expansion of the pro-B/pre-B cell subset in response to NAC treatment suggests oxidative stress normally contributes to cell loss at this developmental stage, and also reveals a potential side effect of therapeutic administration of NAC to prevent smoking-induced loss of lung function.

  12. Fractionation of T cell subsets on Ig anti-Ig columns: isolation of helper T cells from nonresponder mice, demonstration of antigen-specific T suppressor cells, and selection of CD-3 negative variants of Jurkat T cells

    DEFF Research Database (Denmark)

    Rubin, B; Geisler, C; Kuhlmann, J

    1989-01-01

    In the present experiments we have explored the possibilities of a modified immunoadsorbent technique to select for (1) mutagenized T cell receptor (Tcr) negative variants of Jurkat T lymphoma cells and (2) purified CD-4+ or CD-8+ T lymphocytes. The basic principle was to make large numbers...... of immunoglobulin (Ig) negative T cells Ig+ by T cell subset-specific monoclonal antibodies (mAb), and to select such cells on Ig anti-Ig columns. Our results demonstrated that Thy-1+, Fc receptor positive, antigen-specific T cells regulate the immune response in mice nonresponders to pork insulin......." The most important finding is the demonstration of antigen-specific Thy-1+, CD-8+, and Fc receptor+ T suppressor cell that apparently react with antigen in a non-major histocompatibility complex-restricted manner....

  13. MicroRNA-125b expands hematopoietic stem cells and enriches for the lymphoid-balanced and lymphoid-biased subsets.

    Science.gov (United States)

    Ooi, A G Lisa; Sahoo, Debashis; Adorno, Maddalena; Wang, Yulei; Weissman, Irving L; Park, Christopher Y

    2010-12-14

    MicroRNAs profoundly impact hematopoietic cells by regulating progenitor cell-fate decisions, as well as mature immune effector function. However to date, microRNAs that regulate hematopoietic stem cell (HSC) function have been less well characterized. Here we show that microRNA-125b (miR-125b) is highly expressed in HSCs and its expression decreases in committed progenitors. Overexpression of miR-125b in mouse HSC enhances their function, demonstrated through serial transplantation of highly purified HSC, and enriches for the previously described Slamf1(lo)CD34(-) lymphoid-balanced and the Slamf1(neg)CD34(-) lymphoid-biased cell subsets within the multipotent HSC (CD34-KLS) fraction. Mature peripheral blood cells derived from the miR-125b-overexpressing HSC are skewed toward the lymphoid lineage. Consistent with this observation, miR-125b overexpression significantly increases the number of early B-progenitor cells within the spleen and induces the expansion and enrichment of the lymphoid-balanced and lymphoid-biased HSC subset via an antiapoptotic mechanism, reducing the mRNA expression levels of two proapoptotic targets, Bmf and KLF13. The antiapoptotic effect of miR-125b is more pronounced in the lymphoid-biased HSC subset because of their intrinsic higher baseline levels of apoptosis. These effects of miR-125b are associated with the development of lymphoproliferative disease, marked by expansion of CD8(+) T lymphocytes. Taken together, these data reveal that miR-125b regulates HSC survival and can promote lymphoid-fate decisions at the level of the HSC by preferentially expanding lymphoid-balanced and lymphoid-biased HSC.

  14. Expression of ceramide glucosyltransferases, which are essential for glycosphingolipid synthesis, is only required in a small subset of C. elegans cells

    DEFF Research Database (Denmark)

    Marza, Esther; Simonsen, Karina T; Færgeman, Nils J;

    2009-01-01

    mutants with essentially no GSLs. The C. elegans genome encodes three ceramide glucosyltransferase (CGT) genes, which encode enzymes required for GSL biosynthesis. Animals lacking CGT do not synthesize GSLs, arrest growth at the first larval stage, and display defects in a subset of cells...... suggest that GSLs are dispensable in most C. elegans cells, including those of the nervous system.......Glycosphingolipids (GSLs) are glycosylated derivatives of ceramide in the lipid bilayer. Their ubiquitous distribution and complexity suggest that they have important functions, but what these are in vivo is still poorly understood. Here, we characterize the phenotype of Caenorhabditis elegans...

  15. Signal Transduction Involved in Cell Volume Regulation

    NARCIS (Netherlands)

    Th. van der Wijk (Thea)

    2001-01-01

    textabstract1.fammalian cells are surrounded by a selective permeable plasma membrane that allmvs the interior of the cell to differ in composition from the surrounding solution. The plasma membrane is formed by a bilayer of (phospho-) lipids and contains many different proteins. Hydrophobic molecul

  16. The Distribution of HIV DNA and RNA in Cell Subsets Differs in Gut and Blood of HIV-Positive Patients on ART: Implications for Viral Persistence

    Science.gov (United States)

    Yukl, Steven A.; Shergill, Amandeep K.; Ho, Terence; Killian, Maudi; Girling, Valerie; Epling, Lorrie; Li, Peilin; Wong, Lisa K.; Crouch, Pierre; Deeks, Steven G.; Havlir, Diane V.; McQuaid, Kenneth; Sinclair, Elizabeth; Wong, Joseph K.

    2013-01-01

    Even with optimal antiretroviral therapy, human immunodeficiency virus (HIV) persists in plasma, blood cells, and tissues. To develop new therapies, it is essential to know what cell types harbor residual HIV. We measured levels of HIV DNA, RNA, and RNA/DNA ratios in sorted subsets of CD4+ T cells (CCR7+, transitional memory, and effector memory) and non-CD4+ T leukocytes from blood, ileum, and rectum of 8 ART-suppressed HIV-positive subjects. Levels of HIV DNA/million cells in CCR7+ and effector memory cells were higher in the ileum than blood. When normalized by cell frequencies, most HIV DNA and RNA in the blood were found in CCR7+ cells, whereas in both gut sites, most HIV DNA and RNA were found in effector memory cells. HIV DNA and RNA were observed in non-CD4+ T leukocytes at low levels, particularly in gut tissues. Compared to the blood, the ileum had higher levels of HIV DNA and RNA in both CD4+ T cells and non-CD4+ T leukocytes, whereas the rectum had higher HIV DNA levels in both cell types but lower RNA levels in CD4+ T cells. Future studies should determine whether different mechanisms allow HIV to persist in these distinct reservoirs, and the degree to which different therapies can affect each reservoir. PMID:23852128

  17. Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse.

    Science.gov (United States)

    Fukusumi, Yoshiyasu; Meier, Florian; Götz, Sebastian; Matheus, Friederike; Irmler, Martin; Beckervordersandforth, Ruth; Faus-Kessler, Theresa; Minina, Eleonora; Rauser, Benedict; Zhang, Jingzhong; Arenas, Ernest; Andersson, Elisabet; Niehrs, Christof; Beckers, Johannes; Simeone, Antonio; Wurst, Wolfgang; Prakash, Nilima

    2015-09-30

    Wingless-related MMTV integration site 1 (WNT1)/β-catenin signaling plays a crucial role in the generation of mesodiencephalic dopaminergic (mdDA) neurons, including the substantia nigra pars compacta (SNc) subpopulation that preferentially degenerates in Parkinson's disease (PD). However, the precise functions of WNT1/β-catenin signaling in this context remain unknown. Stem cell-based regenerative (transplantation) therapies for PD have not been implemented widely in the clinical context, among other reasons because of the heterogeneity and incomplete differentiation of the transplanted cells. This might result in tumor formation and poor integration of the transplanted cells into the dopaminergic circuitry of the brain. Dickkopf 3 (DKK3) is a secreted glycoprotein implicated in the modulation of WNT/β-catenin signaling. Using mutant mice, primary ventral midbrain cells, and pluripotent stem cells, we show that DKK3 is necessary and sufficient for the correct differentiation of a rostrolateral mdDA neuron subset. Dkk3 transcription in the murine ventral midbrain coincides with the onset of mdDA neurogenesis and is required for the activation and/or maintenance of LMX1A (LIM homeobox transcription factor 1α) and PITX3 (paired-like homeodomain transcription factor 3) expression in the corresponding mdDA precursor subset, without affecting the proliferation or specification of their progenitors. Notably, the treatment of differentiating pluripotent stem cells with recombinant DKK3 and WNT1 proteins also increases the proportion of mdDA neurons with molecular SNc DA cell characteristics in these cultures. The specific effects of DKK3 on the differentiation of rostrolateral mdDA neurons in the murine ventral midbrain, together with its known prosurvival and anti-tumorigenic properties, make it a good candidate for the improvement of regenerative and neuroprotective strategies in the treatment of PD. Significance statement: We show here that Dickkopf 3 (DKK3), a

  18. Giant Merkel Cell Carcinoma Involving the Face

    Directory of Open Access Journals (Sweden)

    Savaş Yaylı

    2012-06-01

    Full Text Available Merkel cell carcinoma is a rare, aggressive, malignant cutaneous tumor. It usually appears on the sun-exposed areas such as the head and neck in the elderly. A 72-year-old female patient was admitted to our clinic with the complaints of a big mass on her face. She described that the mass on her left cheek rapidly grew in three months. Her family and own medical history was unremarkable for skin cancers. On physical examination, there were no pathological findings except for a palpable submandibular lymphadenopathy. Dermatological examination revealed a giant tumoral lesion 9x9 cm in diameter, containing crusted and ulcerated areas on her left cheek. Histopathological examination of the specimen obtained from the lesion showed a neoplastic infiltration consisting small, atypic cells with big, round, hyperchromatic nucleus, narrow cytoplasms, and prominent nucleoulus in some areas, showing high mitotic activity. The neoplasm, which had apoptotic bodies and necrobiosis, also invaded the full thickness of the skin, and the epidermis was very thin. In immunochemistry, CK20 was strongly positive, S100 was focally positive, and EMA was positive, while synaptophysin, chromogranin, vimentin, CD3, CD20, as well as CD45, and CD99 were all negative. Based on these findings, the patient was diagnosed as having Merkel cell carcinoma. On the systemic screening for metastases, nodular lesions in the lungs compatible with metastases were detected on computed tomography. By the consultations with plastic and reconstructive surgeons and oncologists, she was accepted as inoperable and etoposide monotherapy was administered. In this report, we aimed to underline the importance of early diagnosis while presenting a case of giant Merkel cell carcinoma which shows an aggressive progression with lung metastases.

  19. Division of labor: subsets of dorsal-appendage-forming cells control the shape of the entire tube.

    Science.gov (United States)

    Boyle, Michael J; French, Rachael L; Cosand, K Amber; Dorman, Jennie B; Kiehart, Daniel P; Berg, Celeste A

    2010-10-01

    The function of an organ relies on its form, which in turn depends on the individual shapes of the cells that create it and the interactions between them. Despite remarkable progress in the field of developmental biology, how cells collaborate to make a tissue remains an unsolved mystery. To investigate the mechanisms that determine organ structure, we are studying the cells that form the dorsal appendages (DAs) of the Drosophila melanogaster eggshell. These cells consist of two differentially patterned subtypes: roof cells, which form the outward-facing roof of the lumen, and floor cells, which dive underneath the roof cells to seal off the floor of the tube. In this paper, we present three lines of evidence that reveal a further stratification of the DA-forming epithelium. Laser ablation of only a few cells in the anterior of the region causes a disproportionately severe shortening of the appendage. Genetic alteration through the twin peaks allele of tramtrack69 (ttk(twk)), a female-sterile mutation that leads to severely shortened DAs, causes no such shortening when removed from a majority of the DA-forming cells, but rather, produces short appendages only when removed from cells in the very anterior of the tube-forming tissue. Additionally we show that heterotrimeric G-protein function is required for DA morphogenesis. Like TTK69, Gbeta 13F is not required in all DA-forming follicle cells but only in the floor and leading roof cells. The different phenotypes that result from removal of Gbeta 13F from each region demonstrate a striking division of function between different DA-forming cells. Gbeta mutant floor cells are unable to control the width of the appendage while Gbeta mutant leading roof cells fail to direct the elongation of the appendage and the convergent-extension of the roof-cell population.

  20. Langerhans cell histiocytosis with involvement of the pons: case report

    Energy Technology Data Exchange (ETDEWEB)

    Vourtsi, A. [Xatzopoulou, Athens (Greece)]|[Department of Radiology, University of Athens Medical School, Athens (Greece); Papadopoulos, A.; Moulopoulos, L.A.; Vlahos, L. [Department of Radiology, University of Athens Medical School, Athens (Greece); Xenellis, J. [Department of Otorhinolaryngology, University of Athens Medical School, Athens (Greece)

    1998-03-01

    Central nervous system involvement is uncommon in Langerhans cell histiocytosis. The suprasellar region is more frequently affected. There have been few reports of involvement of the brain parenchyma shown on CT or MRI. We present a case of involvement of the pons, showing marked contrast enhancement on MRI. (orig.) With 2 figs., 17 refs.

  1. Effect of radiotherapy on serum SCC, CEA, CRFRA21-1, TAG72, CA199 and lymphocyte subsets in patients with esophageal squamous cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sha Sha; Bo Yu; Zhong-Qin Shu; Xiao-Wei Gu; Wei-Dong Mao; Lin-Yun Xia; Jian-Jun Qin

    2016-01-01

    Objective:To study the effect of radiotherapy on serum SCC, CEA, CRFRA21-1, TAG72, CA199 and lymphocyte subsets in patients with esophageal squamous cell carcinoma. Methods: A total of 60 patients with esophageal squamous cell carcinoma in our hospital from January 2013 to January 2016 were selected as experiment group and 40 healthy subjects were selected as control group. Patients in experiment group were treated with 6MV X-ray radiation therapy. Serum SCC, CEA, CRFRA21-1, TAG72, CA199 and the cell percentage of peripheral blood CD4+, CD8+ were compared in control group and the experimental group before and after 1 month radiotherapy.Results:Before treatment, the levels of serum SCC, CEA and CRFRA21-1 in the experimental group were significantly higher than those in the control group (P0.05). Before treatment, the cell percentage of peripheral blood CD4+, CD8+ and the ratio of CD4+/CD8+ in experimental group was significantly lower than that of the control group, the percentage of peripheral blood CD8+ in the experimental group was significantly higher than that in the control group (P0.05), and in the experimental group, the proportion of CD4+ cells and the tatio of CD4+/CD8+in peripheral blood was significantly lower than that of the control group, the proportion of CD8+ was significantly higher than that of the control group (P<0.05).Conclusions: Radiotherapy can significantly reduce the serum SCC, CEA, CRFRA21-1, TAG72 and CA199 levels of the patients with esophageal squamous cell carcinoma, but have less influence on the T lymphocyte subsets.

  2. Neonatal plasmacytoid dendritic cells (pDCs display subset variation but can elicit potent anti-viral innate responses.

    Directory of Open Access Journals (Sweden)

    Xiaoming Zhang

    Full Text Available Neonates are highly susceptible to infectious diseases and defective antiviral pDC immune responses have been proposed to contribute to this phenomenon. Isolated cord blood pDCs innately responded to a variety of TLR7 and TLR9 dependent viruses, including influenza A virus (IAV, human immunodeficiency virus (HIV or herpes-simplex virus (HSV by efficiently producing IFN-α, TNF-α as well as chemokines. Interestingly, following activation by CpGA, but not viruses, cord pDCs tend to survive less efficiently. We found that a hallmark of pDCs in neonates is an extended CD2+pDCs compartment compared to adult pDCs without affecting the antiviral IFN-α response. Within CD2+pDCs, we identified a subpopulation expressing CD5 and responsible for IL-12p40 production, however this population is significantly decreased in cord blood compared to adult blood. Therefore, neonatal pDCs clearly display variation in phenotype and subset composition, but without major consequences for their antiviral responses.

  3. Presentation of antigen by B cells subsets. Pt. 2. The role of CD5 B cells in the presentation of antigen to antigen-specific T cells

    Energy Technology Data Exchange (ETDEWEB)

    Zimecki, Michal [Polish Academy of Sciences, Wroclaw (Poland). Institute of Immunology and Experimental Therapy; Kapp, Judith A. [Emory Univ., Atlanta, GA (United States). School of Medicine

    1994-12-31

    We demonstrate that peritoneal B cells have a much higher ability to present antigen to antigen-specific T cell lines splenic B cells. Presentation of antigen by B cells is abrogated or drastically reduced after removal of Lyb-5{sup +} cells from the population of splenic or peritoneal B cells. Peritoneal B cells, precultured for 7 days prior to the antigen presentation assay, retain their antigen presenting cell (APC) function. Enrichment for CD5{sup +} cells in the peritoneal B cell population results in a more effective antigen presentation. Lastly, stimulation of B cells via CD5 antigen, by treatment of cells with anti-CD5 antibodies or cross-linking of CD5 receptors, enhances APC function of these cells. The results indicate, both indirectly and directly, that CD5{sup +} B cells play a predominant role in the presentation of conventional antigens to antigen-specific T cells. (author). 30 refs, 6 tabs.

  4. CD161 Expression Defines a Th1/Th17 Polyfunctional Subset of Resident Memory T Lymphocytes in Bronchoalveolar Cells.

    Directory of Open Access Journals (Sweden)

    Yolanda Gonzalez

    Full Text Available Alveolar resident memory T cells (T(RM comprise a currently uncharacterized mixture of cell subpopulations. The CD3(+CD161(+ T cell subpopulation resides in the liver, intestine and skin, but it has the capacity for tissue migration; however, the presence of resident CD3(+CD161(+ T cells in the bronchoalveolar space under normal conditions has not been reported. Bronchoalveolar cells (BACs from healthy volunteers were evaluated and found that 8.6% (range 2.5%-21% of these cells were CD3(+ T lymphocytes. Within the CD3(+ population, 4.6% of the cells (2.1-11.3 expressed CD161 on the cell surface, and 74.2% of the CD161(+CD3(+ T cells expressed CD45RO. The number of CD3(+CD161(+ T cells was significantly lower in the bronchoalveolar space than in the blood (4.6% of BACs vs 8.4% of peripheral blood mononuclear cells (PBMCs; P<0.05. We also found that 2.17% of CD4(+ T lymphocytes and 1.52% of CD8(+ T lymphocytes expressed CD161. Twenty-two percent of the alveolar CD3(+CD161(+ T lymphocytes produced cytokines upon stimulation by PMA plus ionomycin, and significantly more interferon gamma (IFN-γ was produced compared with other cytokines (P = 0.05. Most alveolar CD3(+CD161(+ T cells produced interleukin-17 (IL-17 and IFN-γ simultaneously, and the percentage of these cells was significantly higher than the percentage of CD3(+CD161- T cells. Moreover, the percentage of alveolar CD3(+CD161(+ T lymphocytes that produced IFN-γ/IL-17 was significantly higher than those in the peripheral blood (p<0.05. In conclusion, Th1/Th17-CD3(+CD161(+ TRM could contribute to compartment-specific immune responses in the lung.

  5. A pilot study showing associations between frequency of CD4(+) memory cell subsets at diagnosis and duration of partial remission in type 1 diabetes.

    Science.gov (United States)

    Moya, Rosita; Robertson, Hannah Kathryn; Payne, Dawson; Narsale, Aditi; Koziol, Jim; Davies, Joanna Davida

    2016-05-01

    In some patients with type 1 diabetes the dose of insulin required to achieve euglycemia is substantially reduced soon after diagnosis. This partial remission is associated with β-cell function and good glucose control. The purpose of this study was to assess whether frequencies of CD4(+) T cell subsets in children newly diagnosed with type 1 diabetes are associated with length of partial remission. We found that the frequency of CD4(+) memory cells, activated Treg cells and CD25(+) cells that express a high density of the IL-7 receptor, CD127 (CD127(hi)) are strongly associated with length of partial remission. Prediction of length of remission via Cox regression is significantly enhanced when CD25(+) CD127(hi) cell frequency is combined with either Insulin Dependent Adjusted A1c (IDAA1c), or glycosylated hemoglobin (HbA1c), or C-peptide levels at diagnosis. CD25(+) CD127(hi) cells do not express Foxp3, LAG-3 and CD49b, indicating that they are neither Treg nor Tr1 cells.

  6. Ratiometric analysis of fura red by flow cytometry: a technique for monitoring intracellular calcium flux in primary cell subsets.

    Directory of Open Access Journals (Sweden)

    Emily R Wendt

    Full Text Available Calcium flux is a rapid and sensitive measure of cell activation whose utility could be enhanced with better techniques for data extraction. We describe a technique to monitor calcium flux by flow cytometry, measuring Fura Red calcium dye by ratiometric analysis. This technique has several advantages: 1 using a single calcium dye provides an additional channel for surface marker characterization, 2 allows robust detection of calcium flux by minority cell populations within a heterogeneous population of primary T cells and monocytes 3 can measure total calcium flux and additionally, the proportion of responding cells, 4 can be applied to studying the effects of drug treatment, simultaneously stimulating and monitoring untreated and drug treated cells. Using chemokine receptor activation as an example, we highlight the utility of this assay, demonstrating that only cells expressing a specific chemokine receptor are activated by cognate chemokine ligand. Furthermore, we describe a technique for simultaneously stimulating and monitoring calcium flux in vehicle and drug treated cells, demonstrating the effects of the Gαi inhibitor, pertussis toxin (PTX, on chemokine stimulated calcium flux. The described real time calcium flux assay provides a robust platform for characterizing cell activation within primary cells, and offers a more accurate technique for studying the effect of drug treatment on receptor activation in a heterogeneous population of primary cells.

  7. Distinct myeloid suppressor cell subsets correlate with plasma IL-6 and IL-10 and reduced interferon-alpha signaling in CD4⁺ T cells from patients with GI malignancy.

    Science.gov (United States)

    Mundy-Bosse, Bethany L; Young, Gregory S; Bauer, Todd; Binkley, Elaine; Bloomston, Mark; Bill, Matthew A; Bekaii-Saab, Tanios; Carson, William E; Lesinski, Gregory B

    2011-09-01

    Interferon-alpha (IFN-α) promotes anti-tumor immunity through its actions on immune cells. We hypothesized that elevated percentages of myeloid-derived suppressor cells (MDSC) and increased pro-inflammatory cytokines in peripheral blood would be associated with impaired response to IFN-α in patients with gastrointestinal (GI) malignancies. This study evaluated relationships between plasma IL-6, IL-10, circulating MDSC subsets, and IFN-α-induced signal transduction in 40 patients with GI malignancies. Plasma IL-6 and IL-10 were significantly higher in patients versus normal donors. CD33(+)HLADR(-)CD11b(+)CD15(+) and CD33(+)HLADR(-/low)CD14(+) MDSC subsets were also elevated in patients versus normal donors (P normal donors. Exploratory multivariable Cox proportional hazards models revealed that an increased percentage of the CD33(+)HLADR(-)CD15(-) MDSC subset was associated with reduced overall survival (P = 0.049), while an increased percentage of the CD33(+)HLADR(-/low)CD14(+) subset was associated with greater overall survival (P = 0.033). These data provide evidence for a unique relationship between specific cytokines, MDSC subsets, and IFN-α responsiveness in patients with GI malignancies.

  8. Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

    DEFF Research Database (Denmark)

    Romme Christensen, Jeppe; Börnsen, Lars; Ratzer, Rikke

    2013-01-01

    Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH...... from relapsing-remitting (RRMS) and secondary progressive (SPMS) MS patients. All MS subtypes had decreased frequencies of Th1 TFH-cells, while primary progressive (PPMS) MS patients had increased frequency of Th17 TFH-cells. The Th17-subset, interleukin-23-receptor(+)CD4(+)T-cells, was significantly......, this study is the first to demonstrate the potential involvement of activated TFH-cells in MS. The increased frequencies of Th17-cells, activated TFH- and B-cells parallel findings from pathology studies which, along with the correlation between activated TFH- and B-cells and disease progression, suggest...

  9. Clinical, immunological and treatment-related factors associated with normalised CD4+/CD8+ T-cell ratio: effect of naïve and memory T-cell subsets.

    LENUS (Irish Health Repository)

    Tinago, Willard

    2014-01-01

    Although effective antiretroviral therapy(ART) increases CD4+ T-cell count, responses to ART vary considerably and only a minority of patients normalise their CD4+\\/CD8+ ratio. Although retention of naïve CD4+ T-cells is thought to predict better immune responses, relationships between CD4+ and CD8+ T-cell subsets and CD4+\\/CD8+ ratio have not been well described.

  10. Longitudinal changes of peripheral blood DC subsets and regulatory T cells in Chinese chronic HIV-1-infected patients during antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Mei Zhang

    Full Text Available It has been emphasized that chronic generalized immune dysfunction is the leading event in the pathogenesis of HIV infection, in which the contribution of dendritic cells (DCs and regulatory T cells (Tregs should not be underestimated. In current study, we assessed the longitudinal changes of peripheral blood DC subsets and Tregs in chronically asymptomatic treatment-naive HIV-1-infected patients during 60 weeks of antiretroviral therapy (ART, and compared with those in healthy controls and long term non-progressors (LTNPs. Blood samples were collected at week 0, 4, 12, 24, 48 and 60 of treatment to measure the counts of DC subsets and Tregs by flow cytometry and IFN-a plasma levels by ELISA. The counts of myeloid dendritic cells (mDCs increased during ART, reaching similar levels to healthy controls at week 60 post ART but still lower than those of LTNPs. In HIV-1-infected patients, the mDCs counts were directly correlated with CD4 counts during ART. Changes in mDCs at week 8 were positively correlated with the changes in CD4 counts at week 60 post ART. However, the counts and function of plasmacytoid dendritic cells (pDCs remained relatively stable during ART, and similar to those in healthy controls and LTNPs. The percentage of Tregs increased before ART and normalized after ART. Importantly, we found pDCs counts were associated with percentage of Tregs during ART, which may help in understanding of the role of these cells in HIV infection.

  11. Presentation of antigen by B cells subsets. Pt. 1. Lyb-5{sup +} and Lyb-5{sup -} B cells differ in ability to stimulate specific T cells

    Energy Technology Data Exchange (ETDEWEB)

    Zimecki, M. [Polska Akademia Nauk, Wroclaw (Poland). Inst. Immunologii i Terapii Doswiadczalnej; Whiteley, P.J. [Merck and Co., Inc., Rahway, NJ (United States); Pierce, C.W.; Kapp, J.A. [Harrington Cancer Center, Amarillo (United States). Dept. of Cellular and Molecular Immunology

    1994-12-31

    We have examined the antigen presenting cell (APC) function of different B cells. Resident, peritoneal B cells from normal mice were more efficient than splenic B cells in presenting antigen to CD4{sup +} T cell lines. Peritoneal B cells from X-linked immunodeficient (Xid) mice, by contrast, stimulated no detectable responses. Xid splenic B cells were much less efficient APC than normal splenic B cells. B cells from neonatal mice also were very poor APC until the mice were 3 to 4 weeks old. Xid B cells presented antigen to T cell hybridomas as well as normal B cells showing that they process antigen normally. Thus, the defect is most likely in providing secondary signals. The ability of B cells to present antigen efficiency correlates with the percentage of B cells reported to express the Lyb-5 antigen. Anti-Lyb-5 serum and complement abrogated the APC activity of B cells suggesting that Lyb-5{sup +}, but not Lyb-5{sup -} cells are efficient APC. We also found that activated and resting normal splenic B cells, separated by buoyant density, presented antigen equally. Both populations also contained Lyb-5{sup +} B cells although they were a larger fraction of the activated cells. Lyb-5 is now thought to be an activation antigen rather than a differentiation antigen. If this idea is correct, then our data indicate that anti-Lyb-5 more cleanly separates activated and resting B cells than buoyant density techniques. (author). 38 refs, 7 figs, 1 tab.

  12. Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells.

    Science.gov (United States)

    Carpentier, Sabrina; Vu Manh, Thien-Phong; Chelbi, Rabie; Henri, Sandrine; Malissen, Bernard; Haniffa, Muzlifah; Ginhoux, Florent; Dalod, Marc

    2016-05-01

    Dendritic cells (DC) are mononuclear phagocytes which exhibit a branching (dendritic) morphology and excel at naïve T cell activation. DC encompass several subsets initially identified by their expression of cell surface molecules and later shown to possess distinct functions. DC subset differentiation is orchestrated by transcription factors, growth factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations. There is no standard consensus to identify mononuclear phagocyte subsets; varying antigens are employed depending on the tissue and animal species studied and between laboratories. This has led to confusion in how to accurately define and classify DCs across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC and other mononuclear phagocyte subsets across species. We performed a meta-analysis of several public datasets of human and mouse mononuclear phagocyte subsets isolated from blood, spleen, skin or cutaneous lymph nodes, including by using a novel and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. This analysis demonstrates the equivalence between human and mouse skin XCR1(+) DCs, and between mouse and human Langerhans cells.

  13. Plaque psoriasis vs. atopic dermatitis and lichen planus: a comparison for lesional T-cell subsets, epidermal proliferation and differentiation.

    NARCIS (Netherlands)

    Bovenschen, H.J.; Seijger, M.M.B.; Kerkhof, P.C.M. van de

    2005-01-01

    BACKGROUND: T-cell infiltration in plaque psoriasis has recently been an important subject of investigation. Interestingly, comparative analyses of the disease-specific composition of the lesional T-cell infiltrate in plaque psoriasis and other inflammatory dermatoses have only sparsely been perform

  14. In type 1 diabetes a subset of anti-coxsackievirus B4 antibodies recognize autoantigens and induce apoptosis of pancreatic beta cells.

    Directory of Open Access Journals (Sweden)

    Caterina Bason

    Full Text Available Type 1 diabetes is characterized by autoimmune destruction of pancreatic beta cells. The role played by autoantibodies directed against beta cells antigens in the pathogenesis of the disease is still unclear. Coxsackievirus B infection has been linked to the onset of type 1 diabetes; however its precise role has not been elucidated yet. To clarify these issues, we screened a random peptide library with sera obtained from 58 patients with recent onset type 1 diabetes, before insulin therapy. We identified an immunodominant peptide recognized by the majority of individual patients'sera, that shares homology with Coxsackievirus B4 VP1 protein and with beta-cell specific autoantigens such as phogrin, phosphofructokinase and voltage-gated L-type calcium channels known to regulate beta cell apoptosis. Antibodies against the peptide affinity-purified from patients' sera, recognized the viral protein and autoantigens; moreover, such antibodies induced apoptosis of the beta cells upon binding the L-type calcium channels expressed on the beta cell surface, suggesting a calcium dependent mechanism. Our results provide evidence that in autoimmune diabetes a subset of anti-Coxsackievirus antibodies are able to induce apoptosis of pancreatic beta cells which is considered the most critical and final step in the development of autoimmune diabetes without which clinical manifestations do not occur.

  15. Basaloid squamous cell carcinoma involving floor of the mouth

    Directory of Open Access Journals (Sweden)

    Sah Kunal

    2008-01-01

    Full Text Available Basaloid squamous cell carcinomas of oral mucosa are uncommon. Majority of them can be differentiated from squamous cell carcinoma by their aggressive clinical course and their histopathological features. This case report presents a case of 70-year-old male with basaloid squamous cell carcinoma involving the floor of the mouth.

  16. Effects of Radiofrequency Ablation on Lymphocyte Subsets and Type 1/Type 2 T Cell Subpopulations in Patients with Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yan-bin Wang; Wei-Guo Xu; He-liang Liu; Kun Yan; Lin Ma; Wan-hou Guo

    2009-01-01

    Objective: To evaluate whether radiofrequency ablation (RFA) might have an influence on immune status in hepatocellular carcinoma (HCC) patients. Methods: We measured the T lymphocytes, B lymphocyte and NK cells, and determined the population of Th1, Th2, Tc1 and Tc2 of peripheral blood samples taken from 26 HCC patients before and after RFA. Results: The proportion of Type1 cells (Th1 and Tc1) and NK cells were significantly increased after RFA, especially in patients of the following subgroups: male, age>55 years, pathological grade I-II tumor, clinical stage I-II or Child-Pugh A and B. Conclusion: Type1 cells and NK cells in HCC patients were increased in a short period after RFA.

  17. Two-photon microscopy imaging of thy1GFP-M transgenic mice: a novel animal model to investigate brain dendritic cell subsets in vivo.

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    Full Text Available Transgenic mice expressing fluorescent proteins in specific cell populations are widely used for in vivo brain studies with two-photon fluorescence (TPF microscopy. Mice of the thy1GFP-M line have been engineered for selective expression of green fluorescent protein (GFP in neuronal populations. Here, we report that TPF microscopy reveals, at the brain surface of these mice, also motile non-neuronal GFP+ cells. We have analyzed the behavior of these cells in vivo and characterized in brain sections their immunophenotype.With TPF imaging, motile GFP+ cells were found in the meninges, subarachnoid space and upper cortical layers. The striking feature of these cells was their ability to move across the brain parenchyma, exhibiting evident shape changes during their scanning-like motion. In brain sections, GFP+ cells were immunonegative to antigens recognizing motile cells such as migratory neuroblasts, neuronal and glial precursors, mast cells, and fibroblasts. GFP+ non-neuronal cells exhibited instead the characteristic features and immunophenotype (CD11c and major histocompatibility complex molecule class II immunopositivity of dendritic cells (DCs, and were immunonegative to the microglial marker Iba-1. GFP+ cells were also identified in lymph nodes and blood of thy1GFP-M mice, supporting their identity as DCs. Thus, TPF microscopy has here allowed the visualization for the first time of the motile behavior of brain DCs in situ. The results indicate that the thy1GFP-M mouse line provides a novel animal model for the study of subsets of these professional antigen-presenting cells in the brain. Information on brain DCs is still very limited and imaging in thy1GFP-M mice has a great potential for analyses of DC-neuron interaction in normal and pathological conditions.

  18. The proportion of different IL-17-producing T cell subsets is associated with liver fibrosis in chronic hepatitis C.

    Science.gov (United States)

    Cachem, Fabio C O F; Dias, Aleida S O; Monteiro, Clarice; Castro, José Roberto; Fernandes, Gabriel; Delphim, Letícia; Almeida, Adilson J; Tavares, Felipe; Maciel, Alessandra M A; Amendola-Pires, Marcia M; Brandão-Mello, Carlos E; Bento, Cleonice A M

    2017-01-31

    Studies have suggested the pivotal role of Th1-related cytokines on the outcome of HCV infection. Nevertheless, the role of different IL-17-secreting T cells on chronic hepatitis C (CHC) is less clear. Here, the in vivo IL-1β, IL-6, and IL-17 levels were positively correlated with both alanine aminotransferase (ALT) levels and hepatic lesions. When compared with the control group, CHC patients showed lower proportion of IL-17-secreting (CD4(+) and CD8(+) ) T cells capable of simultaneously producing IL-21. Moreover, the percentage of IL-10-secreting Th17 cells was also lower in CHC patients. Notably, advanced liver lesions were observed amongst those patients with lower percentage levels of IL-17-producing T cells positive for IL-21, IFN-γ and IL-10. In contrast, the severity of hepatic damage was associated with peripheral single IL-17(+) T cells. The percentage of IL-17(+) IL-21-IFN-γ(+) (CD4(+) and CD8(+) ) T cell phenotypes was positively associated with plasma CD14 levels. Finally, elevated levels of circulating CD14 were detected among CHC patients with extensive liver damage. In summary, although preliminary, our results suggest that a balance between different IL-17-producing T cells, associated with peripheral levels of CD14, may be a progress marker for liver disease in chronically HCV-infected patients. This article is protected by copyright. All rights reserved.

  19. Effect of dietary gluten on dendritic cells and innate immune subsets in BALB/c and NOD mice

    DEFF Research Database (Denmark)

    Larsen, Jesper; Weile, Christian; Antvorskov, Julie Christine

    2015-01-01

    The innate immune system is known to play an important role in oral tolerance to dietary antigens. This is important in development of celiac disease (CD) but may also be important in type 1 diabetes (T1D), and could potentially explain the reduced incidence of T1D in mice receiving a gluten......-free (GF) diet. The direct in vivo effect of gluten on innate cells, and particularly dendritic cells (DC) is not sufficiently clarified. Therefore, we wished to investigate the innate cell populations of spontaneous diabetic NOD mice and healthy BALB/c mice kept on a GF or a standard (STD) gluten...... containing diet. We studied, by flow cytometry and reverse transcription-quantitative polymerase chain reaction (qRT-PCR), if dietary gluten induces changes in the activation of DCs and distribution of selected innate cells in lymphoid, pancreatic and intestinal tissues in BALB/c and NOD mice. We found...

  20. Subset selection in regression

    CERN Document Server

    Miller, Alan

    2002-01-01

    Originally published in 1990, the first edition of Subset Selection in Regression filled a significant gap in the literature, and its critical and popular success has continued for more than a decade. Thoroughly revised to reflect progress in theory, methods, and computing power, the second edition promises to continue that tradition. The author has thoroughly updated each chapter, incorporated new material on recent developments, and included more examples and references. New in the Second Edition:A separate chapter on Bayesian methodsComplete revision of the chapter on estimationA major example from the field of near infrared spectroscopyMore emphasis on cross-validationGreater focus on bootstrappingStochastic algorithms for finding good subsets from large numbers of predictors when an exhaustive search is not feasible Software available on the Internet for implementing many of the algorithms presentedMore examplesSubset Selection in Regression, Second Edition remains dedicated to the techniques for fitting...

  1. A subset of osteoblasts expressing high endogenous levels of PPARgamma switches fate to adipocytes in the rat calvaria cell culture model.

    Directory of Open Access Journals (Sweden)

    Yuji Yoshiko

    Full Text Available BACKGROUND: Understanding fate choice and fate switching between the osteoblast lineage (ObL and adipocyte lineage (AdL is important to understand both the developmental inter-relationships between osteoblasts and adipocytes and the impact of changes in fate allocation between the two lineages in normal aging and certain diseases. The goal of this study was to determine when during lineage progression ObL cells are susceptible to an AdL fate switch by activation of endogenous peroxisome proliferator-activated receptor (PPARgamma. METHODOLOGY/PRINCIPAL FINDINGS: Multiple rat calvaria cells within the ObL developmental hierarchy were isolated by either fractionation on the basis of expression of alkaline phosphatase or retrospective identification of single cell-derived colonies, and treated with BRL-49653 (BRL, a synthetic ligand for PPARgamma. About 30% of the total single cell-derived colonies expressed adipogenic potential (defined cytochemically when BRL was present. Profiling of ObL and AdL markers by qRT-PCR on amplified cRNA from over 160 colonies revealed that BRL-dependent adipogenic potential correlated with endogenous PPARgamma mRNA levels. Unexpectedly, a significant subset of relatively mature ObL cells exhibited osteo-adipogenic bipotentiality. Western blotting and immunocytochemistry confirmed that ObL cells co-expressed multiple mesenchymal lineage determinants (runt-related transcription factor 2 (Runx2, PPARgamma, Sox9 and MyoD which localized in the cytoplasm initially, and only Runx2 translocated to the nucleus during ObL progression. Notably, however, some cells exhibited both PPARgamma and Runx2 nuclear labeling with concomitant upregulation of expression of their target genes with BRL treatment. CONCLUSIONS/SIGNIFICANCE: We conclude that not only immature but a subset of relatively mature ObL cells characterized by relatively high levels of endogenous PPARgamma expression can be switched to the AdL. The fact that some Ob

  2. Differential expression of adhesion moleculesshaping the T-cell subset prevalence during the early phase of autoimmune and Trypanosoma cruzi-elicited myocarditis

    Directory of Open Access Journals (Sweden)

    Ana Paula MP Marino

    2003-10-01

    Full Text Available The participation of cell adhesion molecules (CAMs in the establishment of autoimmune and infectious myocarditis is an important matter of investigation and may have therapeutic implication. Trypanosoma cruzi infection induces a CD8-mediated myocarditis in patients with severe cardiomyopathy and experimental animals. Previously, we have proposed that this predominance of CD8+ T-cells is, at least in part, consequence of the differential expression of CAMs on circulating CD8+ lymphocytes. In the present study we investigated the participation of CAMs in shaping the phenotypic nature of the autoimmune CD4-mediated myosin-induced and the CD8-mediated T. cruzi-elicited myocarditis. We provide evidence that the prevalence of a certain T-cell subset inside the inflamed heart reflects the differential profile of the adhesion molecules VLA-4, LFA-1, and ICAM-1 displayed on a large proportion of this particular T-cell population in peripheral blood during the early phase of inflammation. Further, the expression of VCAM-1, ligand for VLA-4, and ICAM-1, counter-receptor for LFA-1, was up-regulated on vascular endothelium and paralleled the entrance of inflammatory cells into the cardiac tissue. Thus, this up-regulated expression of receptors-counter-receptors that regulate T-cell transmigration through the vascular endothelium may have an important role in the pathogenesis of the early phase of both autoimmune and infectious myocarditis.

  3. 寄生虫感染对树突状细胞亚群的影响%Parasitic infection to dendritic cell subsets

    Institute of Scientific and Technical Information of China (English)

    刘晓霞; 朱明; 徐琦; 丁剑冰

    2012-01-01

    Dendritic cells (DCs) are most currently known as a class of professional antigen presenting cells in body, and also are initiators in the primary immune response by strongly activating naive T cells. DCs determine the direction of immune response, in parasitic infection,DCs are heterogeneous cell population. With the changing of physical and chemical environment around DC, the DCs may differentiate into different subsets in their growth and development process. The biological character istics of different DC subsets are quite different. A wide variety of parasites can cause serious harm to host and make complex and changeable mechanism in parasites. The major categories of parasites are protozoa(,Plasjnodium, Leishmania, Tozoplasma gondii) and helminth (Schistosoma, Clonorchis sinensis , Echinococcosis). DCs play an important role in the immune response against the parasitic infection in the host. After the parasite infection, on the one hand, parasites mainly affect DC maturation in host and induce Thl type responses, so this process is conducive to the host anti infection; on the other hand, parasites mainly suppress the normal function of the DC and reduce the body resistance, so it is benefit to parasite growth in body and cause great harm to the host. In recent years, the study about different types of parasitic infection to dendritic cell subsets also fur ther continue. This article provides a review about the source,and the main function and role of the DC subsets in parasite infec tion immunity.%树突状细胞(dendritic cell,DC)是目前已知的体内功能最强的一类专职抗原提呈细胞,同时也是初次免疫应答的始动者,能强有力地激活初始T细胞,并决定机体免疫应答的方向,其在寄生虫感染中的作用越来越受到人们的重视.大量研究表明,DC是一个异质性极大的细胞群体,随着周围理化环境的变化,DC在生长发育过程中分化为不同的亚群,不同DC亚群的生物学特点存在

  4. Nonviral and viral gene transfer into different subsets of human dendritic cells yield comparable efficiency of transfection.

    Science.gov (United States)

    Lundqvist, Andreas; Noffz, Gabriele; Pavlenko, Maxim; Saebøe-Larssen, Stein; Fong, Timothy; Maitland, Norman; Pisa, Pavel

    2002-01-01

    Among the many promising cancer immunotherapeutic strategies, dendritic cells (DC) have become of particular interest. This study aims to optimize a clinical grade protocol for culture and transfection of human DC. Monocytes and CD34(+) hematopoietic stem cells (HSC) from same donor were differentiated under serum-free conditions and analyzed for their susceptibility to several recently described nonviral transfection methods as compared with established virally mediated gene transfer. Nonviral gene transfer methods studied were square-wave electroporation, lipofection, and particle-mediated transfer of plasmid DNA or in vitro transcribed mRNA. We conclude that DNA is not suitable for transduction of DC using nonviral methods. In contrast, mRNA and square-wave electroporation reproducibly yields 60% and 50% transfected monocyte- and CD34(+)-derived DC, respectively, measured at protein level, without affecting the cell viability. Thus, the transfection efficiency of this method is comparable with the 40-90% transgene expression obtained using retroviral (RV) or adenoviral (AdV) vectors in CD34(+)- and monocyte-derived DC, respectively. In monocyte-derived DC, however, the amount of protein expressed per-cell basis was higher after AdV (MOI = 1000) compared with mRNA electroporation-mediated transfer. This is the first study directly demonstrating side-by-side that mRNA electroporation into DC of different origin indeed results in a comparable number of transduced cells as when using virus-mediated gene transfer.

  5. Effect of Metallothionein on Cell Cycle, Apoptosis Rate and Subsets Distribution of Lymphocytes in Peripheral Blood of Dairy Cattle under Heat Stress

    Institute of Scientific and Technical Information of China (English)

    Jiajie LUO; Jun FANG; Lili LI; Bin ZHANG; LiZhuan WU; Zijun LI; Ying PENG; JueXin FAN; XinYi LAN; JinShun ZHAN

    2013-01-01

    [Objective] This study aimed to research the effect of metal othionein on cellcycle, apoptosis rate and subsets distribution of lymphocytes in peripheral blood of dairy cows under heat stress, so as to perfect the regulative mechanism re-searches of MT to anti-heat stress. [Method] Twenty lactating Chinese Holstein cows were randomly divided into four groups (A, B, C and D), and injected with 0, 4.0, 8.0 and 12.0 mg Zn-metal othionein, respectively by intravenous route. Blood sam-ples were col ected at 1st, 16th, 31st, 46th and 61st day, and the dynamic changes of cellcycle, apoptosis rate and subsets distribution of lymphocytes were determined. [Result] The apoptosis rate of cells in group B and C was lower than those in group A by 26.63% (P>0.05) and 24.84% (P>0.05) respectively. The number of cells in the G0/G1 phage in trial groups was increased and the number of cells in the S and G2/M phages tended to decrease, but there were no significant differences (P>0.05). The number of CD3+ T cellin three trial groups was greater than those in group A by 7.02% (P>0.05), 5.45% (P>0.05) and 3.85% (P>0.05) respectively, while the number of CD4+ T cellin trial groups was higher than those in control group by 31.04% (P<0.05), 35.68% (P<0.05) and 39.34% (P<0.05) respectively. The number of CD8+ T celland the levels of CD4+/CD8+ in trial groups were increased observ-ably, but significant difference (P<0.05) was observed in the levels of CD4+/CD8+between groups A and C only. It demonstrated that exogenous Zn-metal othionein can decrease apoptosis rate, improve cellcycle and regulate subsets distribution of lymphocytes in dairy cattle in a dose-dependent manner. [Conclusion] This study wil provide scientific basis for safe utilization of MT in dairy industry.

  6. Defined breast milk EV subsets boost the immune response and skew the T-cell balance towards a regulatory phenotype

    NARCIS (Netherlands)

    Zonneveld, Marijke; Van Herwijnen, Martijn; Brouwers, Jos; Garssen, Johan; Redegeld, Frank; Nolte-'t Hoen, Esther; Wauben, Marca

    2015-01-01

    Introduction: In the past years it has become clear that cell-derived extracellular vesicles (EV) are present in human breast milk and that these EV can play a role in the instruction of the immune system. Since breast milk impacts the development of the neonatal immune system by conveying environme

  7. Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets

    NARCIS (Netherlands)

    Jager, Nynke A.; de Vries, Bastiaan M. Wallis; Hillebrands, Jan-Luuk; Harlaar, Niels J.; Tio, Rene A.; Slart, Riemer H. J. A.; van Dam, Gooitzen M.; Boersma, Hendrikus H.; Zeebregts, Clark J.; Westra, Johanna

    2016-01-01

    In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated. Twenty-three consecutive plaques removed during carotid endarter

  8. Interactions of commensal gut microbes with subsets of B- and T-cells in the murine host

    NARCIS (Netherlands)

    Jiang, HQ; Thurnheer, MC; Zuercher, AW; Boiko, NV; Bos, NA; Cebra, JJ

    2004-01-01

    Although mechanisms operative in the induction and maintenance of specific, adaptive immunity, including 'cognate' B/T interactions, have been extensively studied and defined, we still know little about the mechanisms operative in developing and maintaining B- and T-cell dependent 'natural' immunity

  9. Liver grafts contain a unique subset of natural killer cells that are transferred into the recipient after liver transplantation.

    NARCIS (Netherlands)

    Moroso, V.; Metselaar, H.J.; Mancham, S.; Tilanus, H.W.; Eissens, D.N.; Meer, A. van der; Laan, L.J. van der; Kuipers, E.J.; Joosten, I.; Kwekkeboom, J.

    2010-01-01

    In contrast to other solid organ transplantations, liver grafts have tolerogenic properties. Animal models indicate that donor leukocytes transferred into the recipient after liver transplantation (LTX) play a relevant role in this tolerogenic phenomenon. However, the specific donor cell types invol

  10. Langerhans cell histiocytosis involving central nervous system: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Won Jin; Park, Dong Woo; Lee, Seung Ro; Hahm, Chang Kok; Ju, Kyung Bin [Hanyang University College of Medicine, Seoul (Korea, Republic of); Kim, Sung Tae [Ulsan University College of Medicine, Seoul (Korea, Republic of)

    1997-01-01

    Langerhans cell histiocytosis(LCH) is a systemic disorder characterized by idiopathic proliferation of histiocytes in the reticuloendothelial system; CNS involvement outside the hypothalamus or pituitary gland is uncommon. We present a case of LCH involving the brainstem, cerebellum, and temporal lobes, and also showing hypothalamic involvement. The lesions were isointense or hypointense on T1WI and hyperintense on T2WI, and showed multifocal enhancing nodules on post-contrast CT and Gd-enhanced MRI.

  11. Presentation of antigen by B cell subsets. Pt. 4. Defective T-B cell signalling causes inability to present antigen by B cells from immunodeficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Zimecki, Michal [Polish Academy of Sciences, Wroclaw (Poland). Institute of Immunology and Experimental Therapy; Kapp, Judith A. [Emory Univ., Atlanta, GA (United States). School of Medicine

    1994-12-31

    The purpose of this study was to investigate differences in T-B cell signalling between B cells from normal and immunodeficient mice. B cell blasts from normal and immunodeficient mice expressed comparable levels of membrane-associated IL-1. B cells from normal, but not immunodeficient mice, prefixed with glutar-aldehyde and cultured with thymocytes or a T cell line BK33, induce in T cells production of a factor which causes release of IL-1 by macrophages. This factor, preincubated with B cells from immunodeficient mice significantly enhances their APC function. Furthermore, this cytokine induces expression of Lyb-5 alloantigen on B cells from immunodeficient mice. This effect could be blocked by neutralizing antibodies to IL-6 but not to IL-2, IL-4 or GM-CSF. We conclude that immature B cells from immunodeficient (CBA/N x BALB/c)F{sub 1} mice are unable to stimulate interacting T cells to produce IL-6 and therefore are inefficient antigen presenting cells. (author). 30 refs, 2 figs, 3 tabs.

  12. Effect of dietary gluten on dendritic cells and innate immune subsets in BALB/c and NOD mice.

    Directory of Open Access Journals (Sweden)

    Jesper Larsen

    Full Text Available The innate immune system is known to play an important role in oral tolerance to dietary antigens. This is important in development of celiac disease (CD but may also be important in type 1 diabetes (T1D, and could potentially explain the reduced incidence of T1D in mice receiving a gluten-free (GF diet. The direct in vivo effect of gluten on innate cells, and particularly dendritic cells (DC is not sufficiently clarified. Therefore, we wished to investigate the innate cell populations of spontaneous diabetic NOD mice and healthy BALB/c mice kept on a GF or a standard (STD gluten containing diet. We studied, by flow cytometry and reverse transcription-quantitative polymerase chain reaction (qRT-PCR, if dietary gluten induces changes in the activation of DCs and distribution of selected innate cells in lymphoid, pancreatic and intestinal tissues in BALB/c and NOD mice. We found that a GF diet increased the percentage of macrophages in BALB/c spleen and of CD11c+ DCs in BALB/c and NOD spleen. Strictly gluten-free (SGF diet increased the percentage of CD103+ DCs in BALB/c mice and decreased percentages of CD11b+ DCs in mesenteric and pancreatic lymph nodes in BALB/c mice. SGF diet in BALB/c mice also decreased DC expression of CD40, CCR7 and MHC-II in pancreatic lymph nodes. In conclusion, GF diet changes the composition of the innate immune system in BALB/c and NOD mice and increases expression of DC activation markers in NOD mice. These results contribute to the explanation of the low diabetes incidence in GF NOD mice. This mechanism may be important in development of type 1 diabetes, celiac disease and non-celiac gluten sensitivity.

  13. T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters

    DEFF Research Database (Denmark)

    Pedersen, C; Dickmeiss, E; Gaub, J;

    1990-01-01

    Seven consecutive patients who presented with a severe acute mononucleosis-like illness associated with HIV seroconversion were evaluated by T-cell subset enumerations and measurements of lymphocyte transformation responses to mitogens and antigen during both their primary illness and a 1-year....... We conclude that severe primary HIV infection may be followed by sustained lymphocyte hyporesponsiveness, a sustained low percentage of CD4 lymphocytes and sustained inversion of the CD4:CD8 ratio....... follow-up period. We observed a characteristic pattern of response to primary HIV infection; initial lymphopenia was followed by CD8 lymphocytosis and inversion of the CD4:CD8 ratio. During follow-up, the CD8 count gradually returned to normal, whereas the CD4:CD8 ratio remained inverted because...

  14. The Drosophila SRF homolog is expressed in a subset of tracheal cells and maps within a genomic region required for tracheal development.

    Science.gov (United States)

    Affolter, M; Montagne, J; Walldorf, U; Groppe, J; Kloter, U; LaRosa, M; Gehring, W J

    1994-04-01

    The Drosophila homolog of the vertebrate serum response factor (SRF) was isolated by low stringency hybridization. Nucleotide sequence analysis revealed that the Drosophila SRF homolog (DSRF) codes for a protein that displays 93% sequence identity with human SRF in the MADS domain, the region required for DNA binding, dimerization and interaction with accessory factors. The DSRF gene is expressed during several phases of embryonic development. In the egg, both the RNA and the protein are maternal in origin and slowly decrease in amount during gastrulation. After germ band retraction, high levels of zygotic expression are observed in a distinct subset of peripheral tracheal cells distributed throughout the embryo. Many of these cells are at the tip of tracheal branches and are in direct contact with the target tissues. The DSRF gene was mapped to position 60C on the second chromosome, and overlapping deficiencies which remove the gene were identified. Analysis of tracheal development in embryos carrying these deletions revealed a degeneration of most of the major branches of the tracheal system. Although the initial migration of tracheal cells was not affected in those deficient embryos, many tracheal cells appeared not to maintain their correct position and continued to migrate. Thus, the DSRF gene might play a role in the proper formation and maintenance of the trachea.

  15. Relationship of peripheral blood T cell subset levels and PD-1/PD-L1 expression levels with viral load in patients with asymptomatic HIV infection

    Institute of Scientific and Technical Information of China (English)

    Xi-Li Miao; Si-Qing Mei; Gui-Min Gao

    2016-01-01

    Objective:To study the relationship of different T cell subset levels and PD-1/PD-L1 expression levels in peripheral blood with viral load in patients with asymptomatic HIV infection.Methods:Patients with asymptomatic HIV infection treated in our hospital from April 2012 to October 2015 were selected as the HIV group of the study, healthy subjects during the same period were selected as the control group, and peripheral blood was collected to detect CD3+CD4+CD8-, CD3+CD4-CD8+, CD4+CD25+Foxp3+ and CD4+CD25+CD127low/-cell levels as well as PD-1/PD-L1 expression levels.Results:The number and percentage of CD3+CD4+CD8- cells as well as the number of CD4+CD25+Foxp3+ and CD4+CD25+CD127low/-cells in peripheral blood of HIV group were significantly lower than those of control group, the number and percentage of CD3+CD4-CD8+ cells, the percentage of CD4+CD25+Foxp3+and CD4+CD25+CD127low/- cells as well as the expression levels of PD-L1 and PD-1 on CD4+T cell surface were significantly higher than those of control group, and the expression levels of PD-L1 and PD-1 on CD8+T cell surface were not significantly different from those of control group; the greater the viral load in HIV group, the lower the percentage of CD3+CD4+CD8-, and the higher the percentage of CD3+CD4-CD8+, CD4+CD25+Foxp3+ and CD4+CD25+CD127low/-cells as well the PD-1/PD-L1 positive percentage on CD4+T cell surface in peripheral blood. Conclusions:The immune characteristics of patients with asymptomatic HIV infection are the decreased number of CD4+T cells and the increased number of CD8+T cells as well as the decreased absolute content and increased relative content of CD4+CD25+Treg cells, and PD-1/PD-L1 pathway is the molecular mechanism of HIV to act on CD4+T cells.

  16. Effects of dietary Fusarium mycotoxins on intestinal lymphocyte subset populations, cell proliferation and histological changes in avian lymphoid organs.

    Science.gov (United States)

    Girish, C K; Smith, T K; Boermans, H J; Anil Kumar, P; Girgis, G N

    2010-10-01

    An experiment was conducted to investigate the effects of dietary Fusarium mycotoxins on gut immunity, cell proliferation, and histology of avian lymphoid organs. The efficacy of a polymeric glucomannan mycotoxin adsorbent (GMA) was also determined. Seventy-two one-day-old male turkey poults were fed corn, wheat, and soybean meal-based diets for 21 days. Diets included control grains, contaminated grains and contaminated grains +0.2% GMA. The major contaminant was deoxynivalenol (3.9 μg/g) with lesser amounts of zearalenone (0.67-0.75 μg/g), 15-acetyl-deoxynivalenol (0.34 μg/g) and HT-2 toxin (0.078-0.085 μg/g). T- and B-lymphocyte populations and crypt cellular proliferation in duodenum, jejunum, ileum and cecal tonsil were measured immunohistochemically on day 14 and 21. Histological changes were recorded after 14 and 21 days of feeding. Feeding contaminated grains significantly increased the percentage of B-lymphocytes in ileum on day 14, and reduced (Pcontaminated diets also caused a reduction (Pcontaminated with Fusarium mycotoxins results in adverse effects on gut immunity and mucosal cell proliferation.

  17. CD45RA-Foxp3(low) non-regulatory T cells in the CCR7-CD45RA-CD27+CD28+ effector memory subset are increased in synovial fluid from patients with rheumatoid arthritis.

    Science.gov (United States)

    Matsuki, Fumichika; Saegusa, Jun; Nishimura, Keisuke; Miura, Yasushi; Kurosaka, Masahiro; Kumagai, Shunichi; Morinobu, Akio

    2014-07-01

    Increased numbers of regulatory T (Treg) cells are found in synovial fluid from patients with rheumatoid arthritis (RASF) compared with peripheral blood. However, Treg cells in RASF have been shown to have a decreased capacity to suppress T cells. Here we phenotypically classified CD4+ T cells in RASF into six subsets based on the expression of CD45RA, CCR7, CD27 and CD28, and demonstrated that the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in synovial fluid compared with peripheral blood. In addition, the proportion of Foxp3+ Treg cells in the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in RASF. Furthermore, most of the Foxp3+ Treg cells in RASF were non-suppressive CD45RA-Foxp3(low) non-Treg cells, and the frequency of the non-Treg cells in the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in RASF. Our findings suggest that the pro-inflammatory environment in RA joints may induce the increase of CD45RA-Foxp3(low) non-Treg cells in synovial fluid.

  18. Thrombopoietin mobilizes CD34+ cell subsets into peripheral blood and expands multilineage progenitors in bone marrow of cancer patients with normal hematopoiesis.

    Science.gov (United States)

    Murray, L J; Luens, K M; Estrada, M F; Bruno, E; Hoffman, R; Cohen, R L; Ashby, M A; Vadhan-Raj, S

    1998-03-01

    Thrombopoietin (TPO), the primary regulator of megakaryocytopoiesis, also mediates biologic effects in vitro on hematopoietic cells more primitive than those committed to the megakaryocyte (MK) lineage. To assess the spectrum of hematopoietic effects of recombinant human (rh)TPO in vivo, we evaluated its proliferative effect on bone marrow (BM) progenitor cells, its maturation effect on BM MKs, and its mobilizing effect on peripheral blood (PB) progenitor cells during a phase I clinical laboratory investigation in which rhTPO was administered to cancer patients with normal hematopoiesis. Twelve patients received a single dose of rhTPO (0.3, 0.6, 1.2, or 2.4 microg/kg of body weight) prior to chemotherapy. BM and PB samples from these patients were analyzed 1 to 2 days before (baseline) and 7 days after rhTPO administration. At higher doses (1.2-2.4 microg/kg), rhTPO produced increased concentrations of primitive CD34+Thy-1+Lin-cells (mean 2.1-fold), CD34+mpl+ cells (mean 5.2-fold), CD34+CD41+CD14- promegakaryoblasts (mean 2.9-fold), and myeloerythroid colony-forming cells (mean threefold) in BM. No significant increases in the frequency of BM colony-forming unit (CFU)-MK were observed. Elevated numbers of both immature (2N-8N) and more mature (64N and 128N) CD41+ MKs were detected in BM, with modal ploidy remaining at 16N. Higher doses of rhTPO (1.2-2.4 microg/kg) also induced increased concentrations of CD34+ cell subsets in PB, including both primitive CD34+Thy-1+Lin- (mean 8.8-fold) and MK lineage-committed CD34+CD41+CD14- cells (mean 14.6-fold) as well as various myeloerythroid colony-forming cells (mean 3.6- to 5.5-fold). These results demonstrate that rhTPO given as a single dose not only promotes proliferation and maturation of cells of the MK lineage, but also expands the pool of BM primitive hematopoietic cells. In addition, rhTPO induces mobilization of hematopoietic progenitors into peripheral circulation. The extent to which such multilineage effects on

  19. Exocytosis sensitivity to growth hormone-releasing hormone in subsets of GH cells in rats under different corticosterone conditions. Ultrastructural study using microwave irradiation for fixation and immunocytochemistry.

    Science.gov (United States)

    Ozawa, Hitoshi; Han, Fang; Kawata, Mitsuhiro

    2004-12-01

    Growth hormone (GH) cells in the rat anterior pituitary have been morphologically classified into three subtypes: type I (mature) containing large secretory granules about 350 nm in diameter, type II (intermediate) containing a mixture of large and small granules, and type III (immature) containing small granules about 150 nm in diameter. However, the functional implications of morphological heterogeneity, especially the different sensitivities to growth hormone-releasing hormone (GRH) under different corticosteroid conditions have not been elucidated to date. In the present study, by application of microwave irradiation (MWI) for fixation and immunocytochemistry, new findings of the exocytotic response have been revealed among the subsets of GH cells following adrenalectomy (ADX), corticosterone treatment and/or GRH treatment. The MWI gave effective results for fixation, especially for the permeability of the fixative, and showed good results for immunoelectron microscopy using the protein-A gold method. Moreover, the use of MWI greatly shortened the fixation, processing and immunolabeling times without compromising the quality of ultrastructural preservation and the specificity of labeling. The number of exocytotic figures was low in all subtypes of GH cells in the sham-operated control rats. GRH treatment induced a significant increase in exocytosis in each subtype of GH cells, particularly in type I (mature) and type II (intermediate) GH cells in the control rats. GRH injection to rats for 4 days after ADX also showed an increase in exocytosis, but the degree was significantly less in comparison with the GRH injection in the control group. Corticosterone replacement given to ADX rats induced a clear recovery of the exocytotic response to GRH to the control level. Serum GH content measured by radioimmunoassay correlated with these morphological results. These results suggest that the secretion of GH stimulated by GRH is closely related to corticosteroids, and

  20. Genes involved in centrosome-independent mitotic spindle assembly in Drosophila S2 cells.

    Science.gov (United States)

    Moutinho-Pereira, Sara; Stuurman, Nico; Afonso, Olga; Hornsveld, Marten; Aguiar, Paulo; Goshima, Gohta; Vale, Ronald D; Maiato, Helder

    2013-12-01

    Animal mitotic spindle assembly relies on centrosome-dependent and centrosome-independent mechanisms, but their relative contributions remain unknown. Here, we investigated the molecular basis of the centrosome-independent spindle assembly pathway by performing a whole-genome RNAi screen in Drosophila S2 cells lacking functional centrosomes. This screen identified 197 genes involved in acentrosomal spindle assembly, eight of which had no previously described mitotic phenotypes and produced defective and/or short spindles. All 197 genes also produced RNAi phenotypes when centrosomes were present, indicating that none were entirely selective for the acentrosomal pathway. However, a subset of genes produced a selective defect in pole focusing when centrosomes were absent, suggesting that centrosomes compensate for this shape defect. Another subset of genes was specifically associated with the formation of multipolar spindles only when centrosomes were present. We further show that the chromosomal passenger complex orchestrates multiple centrosome-independent processes required for mitotic spindle assembly/maintenance. On the other hand, despite the formation of a chromosome-enriched RanGTP gradient, S2 cells depleted of RCC1, the guanine-nucleotide exchange factor for Ran on chromosomes, established functional bipolar spindles. Finally, we show that cells without functional centrosomes have a delay in chromosome congression and anaphase onset, which can be explained by the lack of polar ejection forces. Overall, these findings establish the constitutive nature of a centrosome-independent spindle assembly program and how this program is adapted to the presence/absence of centrosomes in animal somatic cells.

  1. New protein involved in the replacement of cell molecules

    DEFF Research Database (Denmark)

    Poulsen, Jesper Buchhave

    2011-01-01

    In collaboration with colleagues from La Trobe University, Australia, scientists at Aarhus University have discovered and defined a novel enzyme involved in the replacement and renewal of cell molecules. The enzyme exerts its function within the so-called mitochondria - small “enclosed” compartme......In collaboration with colleagues from La Trobe University, Australia, scientists at Aarhus University have discovered and defined a novel enzyme involved in the replacement and renewal of cell molecules. The enzyme exerts its function within the so-called mitochondria - small “enclosed...

  2. A short-term increase of the postoperative naturally circulating dendritic cells subsets in flurbiprofen-treated patients with esophageal carcinoma undergoing thoracic surgery

    Science.gov (United States)

    Chai, Xiao-qing; Shu, Shu-hua; Zhang, Xiao-lin; Xie, Yan-hu; Wei, Xin; Wu, Yu-jing; Wei, Wei

    2016-01-01

    The present study evaluated whether flurbiprofen increased the naturally circulating dendritic cells (DCs) subsets in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophageal resection. Compared to healthy donors (n=20), the significantly depressed percentages of plasmacytoid DCs (pDCs), CD1c+ myeloid DCs (mDCs), and CD141+ mDCs among ESCC patients (n=60) were confirmed. Flurbiprofen was administered before skin incision and at the end of operation in group F (n=30), as well as placebo in group C (n=30). The postoperative suppressed percentages of pDCs, CD1c+ mDCs, and CD141+ mDCs increased significantly following the perioperative treatment with flurbiprofen. Flurbiprofen also significantly stimulated the postoperative IFN-f and IL-17 production, but inhibited the immunosuppressive IL-10 and TGF-β levels. Furthermore, flurbiprofen exerted a similar analgesic effect and brought a significantly less sufentanil consumption compared to group C. Taken together, flurbiprofen provided a short-term increase of postoperative naturally circulating DCs in ESCC patients. PMID:26959879

  3. A short-term increase of the postoperative naturally circulating dendritic cells subsets in flurbiprofen-treated patients with esophageal carcinoma undergoing thoracic surgery.

    Science.gov (United States)

    Wang, Di; Yang, Xin-lu; Chai, Xiao-qing; Shu, Shu-hua; Zhang, Xiao-lin; Xie, Yan-hu; Wei, Xin; Wu, Yu-jing; Wei, Wei

    2016-04-01

    The present study evaluated whether flurbiprofen increased the naturally circulating dendritic cells (DCs) subsets in patients with esophageal squamous cell carcinoma (ESCC) undergoing esophageal resection. Compared to healthy donors (n=20), the significantly depressed percentages of plasmacytoid DCs (pDCs), CD1c+ myeloid DCs (mDCs), and CD141+ mDCs among ESCC patients (n=60) were confirmed. Flurbiprofen was administered before skin incision and at the end of operation in group F (n=30), as well as placebo in group C (n=30). The postoperative suppressed percentages of pDCs, CD1c+ mDCs, and CD141+ mDCs increased significantly following the perioperative treatment with flurbiprofen. Flurbiprofen also significantly stimulated the postoperative IFN-f and IL-17 production, but inhibited the immunosuppressive IL-10 and TGF-β levels. Furthermore, flurbiprofen exerted a similar analgesic effect and brought a significantly less sufentanil consumption compared to group C. Taken together, flurbiprofen provided a short-term increase of postoperative naturally circulating DCs in ESCC patients.

  4. Involvement of dendritic cells in autoimmune diseases in children

    Directory of Open Access Journals (Sweden)

    Reed Ann M

    2007-07-01

    Full Text Available Abstract Dendritic cells (DCs are professional antigen-presenting cells that are specialized in the uptake of antigens and their transport from peripheral tissues to the lymphoid organs. Over the last decades, the properties of DCs have been intensely studied and much knowledge has been gained about the role of DCs in various diseases and health conditions where the immune system is involved, particularly in cancer and autoimmune disorders. Emerging clues in autoimmune diseases, suggest that dendritic cell dysregulation might be involved in the development of various autoimmune disorders in both adults and children. However, studies investigating a possible contribution of DCs in autoimmune diseases in the pediatric population alone are scanty. The purpose of this review is to give a general overview of the current literature on the relevance of dendritic cells in the most common autoimmune conditions of childhood.

  5. Impact of surgery and epirubicin intravesical chemotherapy on peripheral blood dendritic cell subsets in patients with superficial urothelial carcinoma of the bladder

    Institute of Scientific and Technical Information of China (English)

    FENG Lang; MA Lin-lin; ZHANG Yu-hai; TIAN Ye; QU Chen-xue; WANG Yang

    2012-01-01

    Background Superficial urothelial carcinoma (SUC) of the bladder is a common urinary tract tumor in China.There is a high recurrence rate of this tumor even after surgery and intravesical instillation.Previous reports have described a suppression of the immune system in cancer patients.Dendritic cells (DCs) play a pivotal role in the induction of an effective antitumor immune response.The aim of this study was to investigate the effects of surgery and epirubicin intravesical chemotherapy (IC) on peripheral blood DCs in subsets of patients with bladder SUC.@@Methods A total of 66 SUC patients and 38 healthy controls were enrolled in this study.All the patients had undergone transurethral resection (TUR) of their cancer and adjunctive IC after tumor removal.The patients were divided into a non-recurrence group (n=40) and a recurrence group (n=26) based on the presence or absence of tumor recurrence.Blood samples were taken preoperatively (PreOP),on postoperative days (POD) 1 and 7,and at postoperative month (POM) 3.Flow cytometric analysis was used for the determination and quantitation of the surface markers CD80 and CD86 in circulating DC subsets.@@Results The preoperative percentages of myeloid dendritic cells (mDCs) and expression of CD80 and CD86 were impaired in SUC patients compared to healthy controls (P <0.05).The percentages of mDCs and these surface markers decreased significantly on POD 1 and increased on POD 7,remaining higher than the preoperative values in POM 3 (P <0.05).The percentages of mDCs,and CD80 and CD86 in the non-recurrence group on PreOP,POD 7,and POM 3 were higher than those in recurrence group.@@Conclusions Surgical removal of SUC and adjunctive IC were associated with improved circulating mDC counts and function.Persistent depression of mDC counts and function after treatment in recurrence patients indicated lower antitumor immunity that may lead to tumor recurrence.

  6. Vessel involvement in giant cell arteritis : an imaging approach

    NARCIS (Netherlands)

    Holm, Pieter W; Sandovici, Maria; Slart, Riemer H.; Glaudemans, Andor W; Rutgers, Abraham; Brouwer, Elisabeth

    2016-01-01

    Vasculitis is classified based on the size of the involved vessels. The two major forms are small vessel vasculitis (SVV) and large vessel vasculitis (LVV). Main forms of LVV are Takayasu Arteritis (TA), Giant Cell Arteritis (GCA), Isolated Aortitis (IA) and Chronic Periaortitis (PC). This manuscrip

  7. Adult Langerhans Cell Histiocytosis with Hepatic and Pulmonary Involvement

    Science.gov (United States)

    Araujo, Bruno; Costa, Francisco; Lopes, Joanne; Castro, Ricardo

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocytes and a late stage with sclerosis of the biliary tree. Pulmonary findings are more common and include multiple nodules in different stages of cavitation, predominantly in the upper lobes. We present a case of adult LCH with pulmonary and biopsy proven liver involvement with resolution of the hepatic findings after treatment. PMID:25977828

  8. Adult Langerhans Cell Histiocytosis with Hepatic and Pulmonary Involvement

    Directory of Open Access Journals (Sweden)

    Bruno Araujo

    2015-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocytes and a late stage with sclerosis of the biliary tree. Pulmonary findings are more common and include multiple nodules in different stages of cavitation, predominantly in the upper lobes. We present a case of adult LCH with pulmonary and biopsy proven liver involvement with resolution of the hepatic findings after treatment.

  9. The involvement of multipotential progenitor cells in Mooren's ulcer.

    Science.gov (United States)

    Lee, In Gul; Ye, Juan; Kim, Jae Chan

    2005-06-30

    The aim of this study was to assess the involvement of multipotential progenitor cells in the pathogenesis of Mooren's ulcer using immunohistochemical staining techniques. Tissue specimens were collected from 3 Mooren's ulcer patients who underwent lamellar keratectomy. Immunohistochemical staining patterns were analyzed using antibodies: CD34, c-kit, STRO-1, CD45RO, VEGF and a-SMA. Strong positive CD34, c-kit and STRO-1 cells were revealed in Mooren's ulcer specimens, especially in the superficial stroma. A few weakly expressed CD34 stroma cells were seen in normal limbal cornea but no immunoreactivity for c-kit and STRO-1 could be found. CD45RO positive T cells were found to have infiltrated in Mooren's ulcer. The immunostaining pattern of VEGF and a- SMA was closely correlated with the degree of expression and the number of CD34 positive cells. Bone marrow-derived multipotential progenitor cells may be involved in the pathogenesis of Mooren's ulcer by synergizing with other factors to amplify autoimmune destructive reactions and to contribute to the regeneration process. Specific therapeutic strategies that target the role of these cells in the disease are warranted.

  10. Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells

    DEFF Research Database (Denmark)

    Nielsen, C H; Albertsen, L; Bendtzen, K;

    2007-01-01

    ) cells play a significant role in most AID. We therefore examined directly, by flow cytometry, the uptake of MTX by the T helper (Th) cells stimulated for 6 days with Candida albicans (CA) or tetanus toxoid (TT), and its consequences with respect to induction of apoptosis. While none of the resting Th...... apoptosis in both undivided and divided Th cells. PHA-induced apoptosis involved activation of caspase-3 and the anti-apoptotic protein Bcl-2 in addition to PARP cleavage, suggesting that PHA induces apoptosis via different pathways than CA and TT. We suggest that the latter are more representative...

  11. Methotrexate induces poly(ADP-ribose) polymerase-dependent, caspase 3-independent apoptosis in subsets of proliferating CD4+ T cells

    DEFF Research Database (Denmark)

    Nielsen, C H; Albertsen, L; Bendtzen, K;

    2007-01-01

    . Exposure of CA-stimulated PBMC to MTX significantly increased their level of cleaved poly(ADP-ribose) polymerase (PARP), and a similar tendency was observed in TT-stimulated cells. Unlike CA and TT, the mitogen phytohaemagglutinin (PHA) induced proliferation of both CD4- and CD4+ T cells, and induced...... apoptosis in both undivided and divided Th cells. PHA-induced apoptosis involved activation of caspase-3 and the anti-apoptotic protein Bcl-2 in addition to PARP cleavage, suggesting that PHA induces apoptosis via different pathways than CA and TT. We suggest that the latter are more representative...

  12. Cytokine profile and lymphocyte subsets in type 2 diabetes

    Directory of Open Access Journals (Sweden)

    C.O. Francisco

    2016-01-01

    Full Text Available Type 2 diabetes mellitus (T2D is a metabolic disease with inflammation as an important pathogenic background. However, the pattern of immune cell subsets and the cytokine profile associated with development of T2D are unclear. The objective of this study was to evaluate different components of the immune system in T2D patients' peripheral blood by quantifying the frequency of lymphocyte subsets and intracellular pro- and anti-inflammatory cytokine production by T cells. Clinical data and blood samples were collected from 22 men (51.6±6.3 years old with T2D and 20 nonsmoking men (49.4±7.6 years old who were matched for age and sex as control subjects. Glycated hemoglobin, high-sensitivity C-reactive protein concentrations, and the lipid profile were measured by a commercially available automated system. Frequencies of lymphocyte subsets in peripheral blood and intracellular production of interleukin (IL-4, IL-10, IL-17, tumor necrosis factor-α, and interferon-γ cytokines by CD3+ T cells were assessed by flow cytometry. No differences were observed in the frequency of CD19+ B cells, CD3+CD8+ and CD3+CD4+ T cells, CD16+56+ NK cells, and CD4+CD25+Foxp3+ T regulatory cells in patients with T2D compared with controls. The numbers of IL-10- and IL-17-producing CD3+ T cells were significantly higher in patients with T2D than in controls (P<0.05. The frequency of interferon-γ-producing CD3+ T cells was positively correlated with body mass index (r=0.59; P=0.01. In conclusion, this study shows increased numbers of circulating IL-10- and IL-17-producing CD3+ T cells in patients with T2D, suggesting that these cytokines are involved in the immune pathology of this disease.

  13. New Subset of Effector T Cells Th17 and Atherosclerosis%效应性T细胞亚群Th17与动脉粥样硬化

    Institute of Scientific and Technical Information of China (English)

    吉庆伟

    2011-01-01

    Thl7 characterized by the production of interleukin (IL)-17 is a newly founded subset of CD4 T effect cells. Thl7 cyto-kines include IL-17, IL-17F, IL-21, tumor nuclear factor-a and so on. Th 17 have been linked to many chronic inflammatory diseases, autoimmune diseases and tumor. Several data indicated that Th17 response may play an important role in the development and progression of atherosclerosis. In this review,we will introduce the role of Thl7 in atherosclerosis.%效应性T细胞亚群Th17是新近发现的效应性T细胞的又一亚群,因分泌细胞因子IL-17而得名.Th17通过分泌多种效应分子如白细胞介素17、17F、21和肿瘤坏死因子-α等与慢性炎症性疾病、自身免疫性疾病和肿瘤等疾病密切相关.研究发现,动脉粥样硬化的发生发展也与Th17功能的异常密切相关,现拟就此进行综述.

  14. Myeloid cell nuclear differentiation antigen is expressed in a subset of marginal zone lymphomas and is useful in the differential diagnosis with follicular lymphoma.

    Science.gov (United States)

    Metcalf, Ryan A; Monabati, Ahmad; Vyas, Monika; Roncador, Giovanna; Gualco, Gabriela; Bacchi, Carlos E; Younes, Sheren F; Natkunam, Yasodha; Freud, Aharon G

    2014-08-01

    The diagnosis of marginal zone lymphomas (MZL) is challenged by the lack of specific markers that distinguish them from other low-grade non-Hodgkin B-cell lymphomas. Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein that labels myelomonocytic cells as well as B lymphocytes that localize to the marginal zone areas of splenic white pulp. We evaluated MNDA expression in a large series of B-cell lymphomas to assess the sensitivity and specificity of this antigen for the characterization of MZL. A total of 440 tissue sections containing extramedullary B-cell lymphomas and 216 bone marrow biopsies containing atypical or neoplastic lymphoid infiltrates were stained for MNDA by immunohistochemistry. Among the extramedullary lymphoma cases, approximately 67% of nodal MZL, 61% of extranodal MZL, and 24% of splenic MZL expressed MNDA. MNDA was also infrequently expressed in other B-cell neoplasms including mantle cell lymphoma (6%), chronic lymphocytic leukemia/small lymphocytic lymphoma (13%), follicular lymphoma (FL) (4%), lymphoplasmacytic lymphoma (25%), and diffuse large B-cell lymphoma (3%). In contrast, MNDA was only expressed in 2.3% of all bone marrow biopsies involved by lymphoid infiltrates, including 2 cases of FL and one case of MZL. Collectively, these data support the inclusion of MNDA in the diagnostic evaluation of extramedullary B-cell lymphomas, particularly those in which the differential diagnosis is between low-grade FL and MZL.

  15. Increased Levels of Plasma Epstein Barr Virus DNA Identify a Poor-Risk Subset of Patients With Advanced Stage Cutaneous T-Cell Lymphoma

    Science.gov (United States)

    Haverkos, Bradley M.; Gru, Alejandro A.; Geyer, Susan M.; Bingman, Anissa K.; Hemminger, Jessica A.; Mishra, Anjali; Wong, Henry K.; Pancholi, Preeti; Freud, Aharon G.; Caligiuri, Michael A.; Baiocchi, Robert A.; Porcu, Pierluigi

    2016-01-01

    Discovering prognostic factors that simultaneously describe tumor characteristics and improve risk stratification is a priority in cutaneous T-cell lymphoma (CTCL). More than a third of advanced stage CTCL patients in this cohort had detectable cell free plasma Epstein–Barr virus (EBV)-DNA (pEBVd) using quantitative real-time polymerase chain reaction. An increased level of pEBVd was highly concordant with EBV (ie, Epstein–Barr virus RNAs) in tumor tissue and was associated with inferior survival. Introduction Outcomes in advanced stage (AS) cutaneous T-cell lymphomas (CTCL) are poor but with great variability. Epstein–Barr virus (EBV) is associated with a subset of non-Hodgkin lymphomas. Frequency of plasma EBV-DNA (pEBVd) detection, concordance with EBV RNA (EBER) in tumor tissue, codetection of plasma cytomegalovirus DNA (pCMVd), and prognostic effect in AS CTCL are unknown. Patients and Methods Patients (n = 46; 2006–2013) with AS CTCL (≥IIB) were retrospectively studied. pEBVd and pCMVd were longitudinally measured using quantitative real-time polymerase chain reaction. EBER in situ hybridization (ISH) was performed on tumor samples. Survival from time of diagnosis (ToD) and time of progression to AS was assessed. Results Plasma EBV-DNA and pCMVd were detected in 37% (17 of 46) and 17% (8 of 46) of AS CTCL patients, respectively. pCMVd detection was significantly more frequent in pEBVd-positive (pEBVd+) than pEBVd− patients (35% vs. 7%; P = .038). Tumor tissue for EBER-ISH was available in 14 of 17 pEBVd+ and 22 of 29 pEBVd− patients; 12 of 14 (85.7%) pEBVd+ patients were EBER+ versus 0 of 22 pEBVd− patients. Frequency of large cell transformation (LCT) tended to be greater in pEBVd+ patients, but was not significant (10 of 14 pEBVd+ vs. 10 of 23 pEBVd−; P = .17). No notable differences in rates of increased levels of serum lactate dehydrogenase (LDH) were observed (17 of 17 pEBVd+ vs. 27 of 29 pEBVd−). pEBVd detection was associated with

  16. Human Mesenchymal Stem Cell-Educated Macrophages Are a Distinct High IL-6-Producing Subset that Confer Protection in Graft-versus-Host-Disease and Radiation Injury Models.

    Science.gov (United States)

    Bouchlaka, Myriam N; Moffitt, Andrea B; Kim, Jaehyup; Kink, John A; Bloom, Debra D; Love, Cassandra; Dave, Sandeep; Hematti, Peiman; Capitini, Christian M

    2017-02-28

    Mesenchymal stem cells (MSCs) have immunosuppressive and tissue repair properties, but clinical trials using MSCs to prevent or treat graft-versus-host disease (GVHD) have shown mixed results. Macrophages (MØs) are important regulators of immunity and can promote tissue regeneration and remodeling. We have previously shown that MSCs can educate MØs toward a unique anti-inflammatory immunophenotype (MSC-educated macrophages [MEMs]); however, their implications for in vivo models of inflammation have not been studied yet. We now show that in comparison with MØs, MEMs have increased expression of the inhibitory molecules PD-L1, PD-L2, in addition to markers of alternatively activated macrophages: CD206 and CD163. RNA-Seq analysis of MEMs, as compared with MØs, show a distinct gene expression profile that positively correlates with multiple pathways important in tissue repair. MEMs also show increased expression of IL-6, transforming growth factor-β, arginase-1, CD73, and decreased expression of IL-12 and tumor necrosis factor-α. We show that IL-6 secretion is controlled in part by the cyclo-oxygenase-2, arginase, and JAK1/STAT1 pathway. When tested in vivo, we show that human MEMs significantly enhance survival from lethal GVHD and improve survival of mice from radiation injury. We show these effects could be mediated in part through suppression of human T cell proliferation and may have attenuated host tissue injury in part by enhancing murine fibroblast proliferation. MEMs are a unique MØ subset with therapeutic potential for the management of GVHD and/or protection from radiation-induced injury.

  17. CD16+ Monocyte Subsets Are Increased in Large Abdominal Aortic Aneurysms and Are Differentially Related with Circulating and Cell-Associated Biochemical and Inflammatory Biomarkers

    Directory of Open Access Journals (Sweden)

    Giorgio Ghigliotti

    2013-01-01

    Full Text Available Proinflammatory components are present in abdominal aortic aneurysm (AAA. Circulating monocytes display heterogeneity, and three subsets have been identified, based on the differential expression for CD14 and CD16 receptors: CD14+CD16-, classical, CD14+CD16+, intermediate and CD14dim CD16+, non-classical monocytes. Increased proinflammatory CD16+ monocytes with high expression of CD143 are present in CKD patients. D-dimer is increased in AAA patients, and might contribute to the pro-inflammatory response associated to circulating monocytes. We aimed to investigate the frequency of CD14+CD16+, CD14dim CD16+ monocytes and monocyte CD143 expression in AAA patients, and their relationship with D-dimer, eGFR and other inflammatory parameters. Blood from 74 AAA patients and 30 healthy controls was analyzed to determine the frequency of CD14+, CD16+, CD14dim CD16+ monocytes and the monocyte CD143 expression by means of flow-cytometry. AAA patients had expanded CD16+ SUPsets (CD14+CD16+: 7.66 ± 0.31% vs 5.42 ± 0.27%; CD14dim CD16+: 7.43 ± 0.48% vs 5.54 ± 0.38%, AAA vs controls, mean ± SE, both p<0.05. CD14+ CD16+ cells were associated to D-dimer and age, and to reduced eGFR. CD14dim CD16+ cells were associated to uric acid, surface CD143, and reduced count of total leukocytes and neutrophils. Within AAA patients, the two CD16+ supsets and the monocyte CD143 expression display different relationships with D-dimer, parameters of renal function and circulating biochemical and inflammatory biomarkers.

  18. A subset of human pancreatic beta cells express functional CD14 receptors: a signaling pathway for beta cell-related glycolipids, sulfatide and ß-galactosylceramide

    DEFF Research Database (Denmark)

    Østerbye, Thomas; Funda, David P; Fundová, Petra;

    2010-01-01

    T1DM is a T-cell-mediated autoimmune disease targeting insulin-producing beta-cells. Multiple factors may contribute to the development of T1DM. Among these, the metabolic state of beta-cells and pro-inflammatory cytokines, produced by infiltrating immune cells, have been implicated in the precip...

  19. A Novel Inhibitor Of Topoisomerase I is Selectively Toxic For A Subset of Non-Small Cell Lung Cancer Cell Lines | Office of Cancer Genomics

    Science.gov (United States)

    SW044248, identified through a screen for chemicals that are selectively toxic for NSCLC cell lines, was found to rapidly inhibit macromolecular synthesis in sensitive, but not in insensitive cells. SW044248 killed approximately 15% of a panel of 74 NSCLC cell lines and was non-toxic to immortalized human bronchial cell lines.

  20. Cerebellar and basal ganglion involvement in Langerhans cell histiocytosis

    Energy Technology Data Exchange (ETDEWEB)

    Saatci, I.; Baskan, O.; Haliloglu, M.; Aydingoz, U. [Department of Radiology, Hacettepe University Hospital, Sihhiye 06100, Ankara (Turkey)

    1999-06-01

    Langerhans cell histiocytosis (LCH) is a disease of unknown cause characterised by proliferation of histiocytic granulomas in tissues; the primary cerebral manifestation is diabetes insipidus caused by hypothalamic infiltration. We present a patient in whom, except for the absence of high signal on T 1 weighting in the posterior pituitary, consistent with central diabetes insipidus, MRI showed no evidence of hypothalamic involvement by histiocytosis, despite the long duration of the disease. However, there was bilateral, symmetrical involvement of the cerebellum and globus pallidus in addition to a calvarial lesion. High signal in the cerebellar white matter on T 2-weighted images may represent demyelination, gliosis and cell loss, as previously reported on pathologic examination. (orig.) With 5 figs., 22 refs.

  1. Pathogenesis of scrapie in ARQ/ARQ sheep after subcutaneous infection: effect of lymphadenectomy and immune cell subset changes in relation to prion protein accumulation.

    Science.gov (United States)

    Chianini, F; Sisó, S; Ricci, E; Eaton, S L; Finlayson, J; Pang, Y; Hamilton, S; Steele, P; Reid, H W; Cantile, C; Sales, J; Jeffrey, M; Dagleish, M P; González, L

    2013-04-15

    It is well established that the infectious agent of scrapie can replicate in the lymphoreticular system (LRS). However, the effects of removal of LRS target tissues on the pathogenesis of the infection and the accumulation of disease-associated prion protein (PrP(d)) in LRS tissues on specific immune cell subsets are poorly understood aspects. To address these questions 16 ARQ/ARQ sheep were subcutaneously inoculated in the drainage area of the prefemoral lymph node with brain homogenate derived from Suffolk sheep naturally infected with scrapie. Fourteen sheep were then subjected to either early (14-17 days post-inoculation [dpi]) or late (175-201 dpi) lymphadenectomy and culled at preclinical or clinical stages of infection. Neither late nor even early lymphadenectomy prevented infection or had any effect on the accumulation of PrP(d) in the LRS or CNS suggesting a rapid organic dissemination of the infectious agent after inoculation. Lymph nodes from eight scrapie inoculated sheep selected on the basis of the amount of PrP(d) in their LRS tissues (negative, low or high) were examined for six different immune cell markers. The PrP(d) negative lymph nodes from two sheep with no evidence of scrapie infection showed lower numbers of cluster of determination (CD) 21 positive cells than PrP(d) positive nodes, irrespective of their location (hind leg or head). However, quantitative differences in the expression of this marker were not detected when comparing lymph nodes with low and high levels of PrP(d) accumulation, suggesting that proliferation of CD21 positive cells is related to scrapie infection, but not directly linked to the magnitude of PrP(d) accumulation. An additional observation of the study was that sheep that were methionin-threonine at codon 112 of the prion protein gene showed lower attack rates than methionine homozygotes (67% and 100%, respectively) and also generally lower levels of PrP(d) accumulation in the LRS and brain and increased survival

  2. CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease.

    Directory of Open Access Journals (Sweden)

    Guillaume Sarrabayrouse

    2014-04-01

    Full Text Available How the microbiota affects health and disease is a crucial question. In mice, gut Clostridium bacteria are potent inducers of colonic interleukin (IL-10-producing Foxp3 regulatory T cells (Treg, which play key roles in the prevention of colitis and in systemic immunity. In humans, although gut microbiota dysbiosis is associated with immune disorders, the underlying mechanism remains unknown. In contrast with mice, the contribution of Foxp3 Treg in colitis prevention has been questioned, suggesting that other compensatory regulatory cells or mechanisms may exist. Here we addressed the regulatory role of the CD4CD8 T cells whose presence had been reported in the intestinal mucosa and blood. Using colonic lamina propria lymphocytes (LPL and peripheral blood lymphocytes (PBL from healthy individuals, and those with colon cancer and irritable bowel disease (IBD, we demonstrated that CD4CD8αα (DP8α T lymphocytes expressed most of the regulatory markers and functions of Foxp3 Treg and secreted IL-10. Strikingly, DP8α LPL and PBL exhibited a highly skewed repertoire toward the recognition of Faecalibacterium prausnitzii, a major Clostridium species of the human gut microbiota, which is decreased in patients with IBD. Furthermore, the frequencies of DP8α PBL and colonic LPL were lower in patients with IBD than in healthy donors and in the healthy mucosa of patients with colon cancer, respectively. Moreover, PBL and LPL from most patients with active IBD failed to respond to F. prausnitzii in contrast to PBL and LPL from patients in remission and/or healthy donors. These data (i uncover a Clostridium-specific IL-10-secreting Treg subset present in the human colonic LP and blood, (ii identify F. prausnitzii as a major inducer of these Treg, (iii argue that these cells contribute to the control or prevention of colitis, opening new diagnostic and therapeutic strategies for IBD, and (iv provide new tools to address the systemic impact of both these Treg

  3. Rare giant cell tumor involvement of the olecranon bone.

    Science.gov (United States)

    Yang, Chen; Gong, Yubao; Liu, Jianguo; Qi, Xin

    2014-06-01

    Giant cell tumor (GCT) of bone is a relatively common benign bone lesion and is usually located in long bones, but involvement of the olecranon is extremely rare. Here, we present a case of solitary GCT of bone in the olecranon that was confirmed by preoperative needle biopsy and postoperative histological examination. The treatment included intralesional curettage, allogeneic bone grafting, and plating. At 26 months follow-up, the patient had no local recurrence.

  4. Rare giant cell tumor involvement of the olecranon bone

    Directory of Open Access Journals (Sweden)

    Chen Yang

    2014-01-01

    Full Text Available Giant cell tumor (GCT of bone is a relatively common benign bone lesion and is usually located in long bones, but involvement of the olecranon is extremely rare. Here, we present a case of solitary GCT of bone in the olecranon that was confirmed by preoperative needle biopsy and postoperative histological examination. The treatment included intralesional curettage, allogeneic bone grafting, and plating. At 26 months follow-up, the patient had no local recurrence.

  5. Lipid raft involvement in yeast cell growth and death.

    Science.gov (United States)

    Mollinedo, Faustino

    2012-01-01

    The notion that cellular membranes contain distinct microdomains, acting as scaffolds for signal transduction processes, has gained considerable momentum. In particular, a class of such domains that is rich in sphingolipids and cholesterol, termed as lipid rafts, is thought to compartmentalize the plasma membrane, and to have important roles in survival and cell death signaling in mammalian cells. Likewise, yeast lipid rafts are membrane domains enriched in sphingolipids and ergosterol, the yeast counterpart of mammalian cholesterol. Sterol-rich membrane domains have been identified in several fungal species, including the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe as well as the pathogens Candida albicans and Cryptococcus neoformans. Yeast rafts have been mainly involved in membrane trafficking, but increasing evidence implicates rafts in a wide range of additional cellular processes. Yeast lipid rafts house biologically important proteins involved in the proper function of yeast, such as proteins that control Na(+), K(+), and pH homeostasis, which influence many cellular processes, including cell growth and death. Membrane raft constituents affect drug susceptibility, and drugs interacting with sterols alter raft composition and membrane integrity, leading to yeast cell death. Because of the genetic tractability of yeast, analysis of yeast rafts could be an excellent model to approach unanswered questions of mammalian raft biology, and to understand the role of lipid rafts in the regulation of cell death and survival in human cells. A better insight in raft biology might lead to envisage new raft-mediated approaches to the treatment of human diseases where regulation of cell death and survival is critical, such as cancer and neurodegenerative diseases.

  6. Lipid raft involvement in yeast cell growth and death

    Directory of Open Access Journals (Sweden)

    Faustino eMollinedo

    2012-10-01

    Full Text Available The notion that cellular membranes contain distinct microdomains, acting as scaffolds for signal transduction processes, has gained considerable momentum. In particular, a class of such domains that is rich in sphingolipids and cholesterol, termed as lipid rafts, is thought to compartmentalize the plasma membrane, and to have important roles in survival and cell death signaling in mammalian cells. Likewise, yeast lipid rafts are membrane domains enriched in sphingolipids and ergosterol, the yeast counterpart of mammalian cholesterol. Sterol-rich membrane domains have been identified in several fungal species, including the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe as well as the pathogens Candida albicans and Crytococcus neoformans. Yeast rafts have been mainly involved in membrane trafficking, but increasing evidence implicates rafts in a wide range of additional cellular processes. Yeast lipid rafts house biologically important proteins involved in the proper function of yeast, such as proteins that control Na+, K+ and pH homeostasis, which influence many cellular processes, including cell growth and death. Membrane raft constituents affect drug susceptibility, and drugs interacting with sterols alter raft composition and membrane integrity, leading to yeast cell death. Because of the genetic tractability of yeast, analysis of yeast rafts could be an excellent model to approach unanswered questions of mammalian raft biology, and to understand the role of lipid rafts in the regulation of cell death and survival in human cells. A better insight in raft biology might lead to envisage new raft-mediated approaches to the treatment of human diseases where regulation of cell death and survival is critical, such as cancer and neurodegenerative diseases.

  7. B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients.

    Science.gov (United States)

    Marasco, Emiliano; Farroni, Chiara; Cascioli, Simona; Marcellini, Valentina; Scarsella, Marco; Giorda, Ezio; Piano Mortari, Eva; Leonardi, Lucia; Scarselli, Alessia; Valentini, Diletta; Cancrini, Caterina; Duse, Marzia; Grimsholm, Ola; Carsetti, Rita

    2017-01-01

    Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naïve and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system.

  8. MCL-1 is required throughout B-cell development and its loss sensitizes specific B-cell subsets to inhibition of BCL-2 or BCL-XL

    NARCIS (Netherlands)

    Vikström, Ingela B; Slomp, Anne; Carrington, Emma M; Moesbergen, Laura M; Chang, Catherine; Kelly, Gemma L; Glaser, Stefan P; Jansen, J H Marco; Leusen, Jeanette H W; Strasser, Andreas; Huang, David C S; Lew, Andrew M; Peperzak, Victor; Tarlinton, David M

    2016-01-01

    Pro-survival BCL-2 family members protect cells from programmed cell death that can be induced by multiple internal or external cues. Within the haematopoietic lineages, the BCL-2 family members BCL-2, BCL-XL and MCL-1 are known to support cell survival but the individual and overlapping roles of th

  9. Reliability analysis of slope stability involving correlated non-normal variables using subset simulation method%含相关非正态变量边坡可靠度分析的子集模拟方法

    Institute of Scientific and Technical Information of China (English)

    张曼; 唐小松; 李典庆

    2012-01-01

    提出了分析含相关非正态变量高维小失效概率可靠度问题的子集模拟方法,采用Nataf变换方法成功地解决了输入变量相关时子集模拟方法样本点的模拟问题.编写了基于MATLAB语言的计算程序SUBSETREL,并以岩质边坡稳定可靠度问题为例证明了所提方法的有效性.结果表明:该子集模拟方法能够有效地分析含相关非正态变量高维小失效概率的边坡可靠度问题.子集模拟方法的计算精度和蒙特卡洛模拟方法相当,计算效率远远高于传统的蒙特卡洛模拟方法.此外,该方法在分析含有复杂的隐式及非线性功能函数的边坡可靠度问题方面体现出明显的优越性.研究成果极大地拓展了子集模拟方法在边坡可靠度分析中的应用.%This paper aims to propose a reliability method named subset simulation(SS) method for estimation of small failure probability in high dimensions of slope stability problems involving correlated non-normal random variables.The Nataf transformation is used to transform the correlated non-normal random variables into the independent standard normal variables,which facilitates the simulation of correlated non-normal samples in failure domain and reliability computation using the SS method.A MATLAB-language based computer program called SUBSETREL is developed to carry out the reliability computations.Two examples of reliability analysis for rock slope stability with plane failure are presented to demonstrate the validity and capability of the proposed method.The results indicate that the proposed SS method can compute small failure probability in high dimensions of rock slope stability involving correlated non-normal random variables accurately and efficiently.Furthermore,the proposed SS method can result in the same accuracy as the traditional Monte Carlo simulations;and its efficiency is significantly higher than the traditional Monte Carlo simulations,which can be considered as

  10. TCR usage, gene expression and function of two distinct FOXP3(+)Treg subsets within CD4(+)CD25(hi) T cells identified by expression of CD39 and CD45RO.

    Science.gov (United States)

    Ye, Lingying; Goodall, Jane C; Zhang, Libin; Putintseva, Ekaterina V; Lam, Brian; Jiang, Lei; Liu, Wei; Yin, Jian; Lin, Li; Li, Ting; Wu, Xin; Yeo, Giles; Shugay, Mikhail; Chudakov, Dmitriy M; Gaston, Hill; Xu, Huji

    2016-03-01

    FOXP3+ regulatory T (Treg) cells are indispensable for immune homeostasis, but their study in humans is complicated by heterogeneity within Treg, the difficulty in purifying Tregs using surface marker expression (e.g. CD25) and the transient expression of FOXP3 by activated effector cells. Here, we report that expression of CD39 and CD45RO distinguishes three sub-populations within human CD4(+)CD25(hi) T cells. Initial phenotypic and functional analysis demonstrated that CD4(+)CD25(hi)CD39(+)CD45RO(+) cells had properties consistent with effector Treg, CD4(+)CD25(hi)CD39(-)CD45RO(-) cells were naïve Treg and CD4(+)CD25(hi)CD39(-)CD45RO(+) cells were predominantly non-Treg with effector T-cell function. Differences in these two newly identified Treg subsets were corroborated by studies of gene expression and TCR analysis. To apply this approach, we studied these two newly identified Treg subsets in ankylosing spondylitis, and showed impairment in both effector and naïve Treg. This work highlights the importance of discriminating Treg subsets to enable proper comparisons of immune regulatory capacity in healthy individuals and those with inflammatory disease.

  11. Human bladder cancer stem cells exist in epithelial membrane antigen-subset%人膀胱癌干细胞存在于EMA-细胞亚群

    Institute of Scientific and Technical Information of China (English)

    杨宇明; 畅继武

    2008-01-01

    BACKGROUND:Cancer stem cell (CSC) hypothesis suggests that tumorous clones are maintained by a rare fraction of cells with stem cell proprieties. Several kinds of CSCs of solid tumor have been isolated in recent years. However, there have been fewer studies on the objective existence of bladder cancer stem cells (BCSCs) and on the methods to effectively isolate and identify BCSCs. OBJECTIVE:To investigate possibilities of BCSC existence and of epithelial membrane antigen (EMA) used as a surface marker of BCSC. DESIGN:A control observation experiment. SETTING:Tianjin Institute of Urinary Surgery & Second Hospital of Tianjin Medical University. MATERIALS:This study was performed at the Room for Tumor Immunity of Tianjin Institute of Urinary Surgery (key laboratory for State "211 Project") from March 2006 to July 2007. Nine specimens of human bladder were obtained from patients who received treatment in the Second Hospital of Tianjin Medical University. These specimens corresponded to the diagnostic criteria of low malignant potential papillary urothelial neoplasm and low-grade papillary urothelial carcinoma. Additionally, 40 samples of human low malignant bladder transitional cell carcinomas (BTCC) and 10 samples of normal urothelium that were used for immunohistochemistry were obtained from the patients who received treatment in the Department of Urinary Surgery, Second Hospital of Tianjin Medical University. Written informed consent for the specimen providing was obtained from the patients, and the protocol was approved by the hospital’s Ethics Committee. METHODS:The genes that were differentially expressed between normal urothelium and BTCC were identified through a DNA array assay to preliminarily determine the existence of BTCC. Overpressed stem cell related genes, Bmi-1 and EZH2, were verified by immunohistochemistry. A total of 27 potential surface markers of BCSCs were assayed to determine the location of positive cells. EMA- subsets were obtained through

  12. Predictive validity and immune cell involvement in the pathogenesis of piroxicam-accelerated colitis in interleukin-10 knockout mice

    DEFF Research Database (Denmark)

    Holgersen, Kristine; Kvist, Peter Helding; Hansen, Axel Jacob Kornerup

    2014-01-01

    prednisolone treatment. To evaluate cell involvement in the disease pathogenesis, specific cell subsets were depleted by treatment with anti-CD4 mAb, anti-CD8 mAb or clodronate-encapsulated liposomes. T cell receptor co-stimulation was blocked by CTLA4-Ig. Cytokine profiling ELISAs and calprotectin...... immunohistochemistry were performed on colon tissue. Treatments with anti-IL-12/23p40 mAb and CsA prevented disease in PAC IL-10 k.o. mice and reduced IFNγ, IL-17A, MPO and calprotectin levels in colon. Anti-TNFαmAb treatment caused amelioration of selected clinical parameters. No effect of prednisolonewas detected...

  13. Histamine and histamine-receptor antagonists modify gene expression and biosynthesis of interferon gamma in peripheral human blood mononuclear cells and in CD19-depleted cell subsets

    NARCIS (Netherlands)

    Horváth, B V; Szalai, C; Mándi, Y; László, V; Radvány, Z; Darvas, Z; Falus, A

    1999-01-01

    The effect of histamine and histamine antagonists was examined on gene expression and biosynthesis of bacterial endotoxin (LPS) induced interferon gamma (IFNgamma) both in human peripheral mononuclear cells (PMBC) and in T-cell enriched fractions. We found, that histamine inhibited the LPS induced t

  14. Liver involvement of Langerhans’ cell histiocytosis in children

    Science.gov (United States)

    Yi, Xiaoping; Han, Tong; Zai, Hongyan; Long, Xueying; Wang, Xiaoyi; Li, Wenzheng

    2015-01-01

    Objective: Liver involvement is relatively frequent in children with Langerhans cell histiocytosis (LCH). Its features remain poorly defined. Methods: A retrospective study was carried out on 14 hepatic LCH children in our hospital. The Clinicopathological and radiological features of this disease was discussed. Results: The rate of liver involvement in children LCH patients is 51.9%. Majority of the patients were disseminated cases. Hepatomegaly was clinically confirmed in 11 cases (78.6%). Liver function dysfunction was seen in nine (64.3%) children. The association of multi-modal imaging significantly yielded more diagnostic information. There are some imaging characteristics of this disease, CT and MRI could help to assess the staging, extent of the hepatic lesions. We found that liver involvement had a significant impact on survival. Patients treated with systemic chemotherapy earlier from time of diagnosis had a relatively better outcome. Conclusions: The rate of liver involvement in children LCH patients maybe much higher than that of expected. We suggest that clinical and biological liver evaluation and abdominal imaging must be performed regularly onwards to screen every LCH children patient from the time of the initial diagnosis. Patient should be treated with systemic chemotherapy earlier. PMID:26221247

  15. Immune receptors involved in Streptococcus suis recognition by dendritic cells.

    Directory of Open Access Journals (Sweden)

    Marie-Pier Lecours

    Full Text Available Streptococcus suis is an important swine pathogen and an emerging zoonotic agent of septicemia and meningitis. Knowledge on host immune responses towards S. suis, and strategies used by this pathogen for subversion of these responses is scarce. The objective of this study was to identify the immune receptors involved in S. suis recognition by dendritic cells (DCs. Production of cytokines and expression of co-stimulatory molecules by DCs were shown to strongly rely on MyD88-dependent signaling pathways, suggesting that DCs recognize S. suis and become activated mostly through Toll-like receptor (TLR signaling. Supporting this fact, TLR2(-/- DCs were severely impaired in the release of several cytokines and the surface expression of CD86 and MHC-II. The release of IL-12p70 and CXC10, and the expression of CD40 were found to depend on signaling by both TLR2 and TLR9. The release of IL-23 and CXCL1 were partially dependent on NOD2. Finally, despite the fact that MyD88 signaling was crucial for DC activation and maturation, MyD88-dependent pathways were not implicated in S. suis internalization by DCs. This first study on receptors involved in DC activation by S. suis suggests a major involvement of MyD88 signaling pathways, mainly (but not exclusively through TLR2. A multimodal recognition involving a combination of different receptors seems essential for DC effective response to S. suis.

  16. Prediction based on mean subset

    DEFF Research Database (Denmark)

    Øjelund, Henrik; Brown, P. J.; Madsen, Henrik;

    2002-01-01

    , it is found that the proposed mean subset method has superior prediction performance than prediction based on the best subset method, and in some settings also better than the ridge regression and lasso methods. The conclusions drawn from the Monte Carlo study is corroborated in an example in which prediction......Shrinkage methods have traditionally been applied in prediction problems. In this article we develop a shrinkage method (mean subset) that forms an average of regression coefficients from individual subsets of the explanatory variables. A Bayesian approach is taken to derive an expression of how...

  17. miRNA profiling of B-cell subsets : specific miRNA profile for germinal center B cells with variation between centroblasts and centrocytes

    NARCIS (Netherlands)

    Tan, Lu Ping; Wang, Miao; Robertus, Jan-Lukas; Schakel, Rikst Nynke; Gibcus, Johan H.; Diepstra, Arjan; Harms, Geert; Peh, Suat-Cheng; Reijmers, Rogier M.; Pals, Steven T.; Kroesen, Bart-Jan; Kluin, Philip M.; Poppema, Sibrand; van den Berg, Anke

    2009-01-01

    MicroRNAs ( miRNAs) are an important class of small RNAs that regulate gene expression at the post-transcriptional level. It has become evident that miRNAs are involved in hematopoiesis, and that deregulation of miRNAs may give rise to hematopoietic malignancies. The aim of our study was to establis

  18. Some effects of non-surgical therapy on gingival inflammatory cell subsets in patients with adult and early-onset periodontitis

    NARCIS (Netherlands)

    Kleinfelder, JW; Lange, DE; Bocker, W

    2000-01-01

    Background: Limited information is available to determine if there is a distinction in local cellular immunity between adult and early-onset periodontitis. Furthermore, the effect of scaling and root planing on various lymphocyte subsets is sparsely described. Methods: Clinical measurements were rec

  19. HIV-infected individuals with low CD4/CD8 ratio despite effective antiretroviral therapy exhibit altered T cell subsets, heightened CD8+ T cell activation, and increased risk of non-AIDS morbidity and mortality.

    Directory of Open Access Journals (Sweden)

    Sergio Serrano-Villar

    2014-05-01

    Full Text Available A low CD4/CD8 ratio in elderly HIV-uninfected adults is associated with increased morbidity and mortality. A subset of HIV-infected adults receiving effective antiretroviral therapy (ART fails to normalize this ratio, even after they achieve normal CD4+ T cell counts. The immunologic and clinical characteristics of this clinical phenotype remain undefined. Using data from four distinct clinical cohorts and three clinical trials, we show that a low CD4/CD8 ratio in HIV-infected adults during otherwise effective ART (after CD4 count recovery above 500 cells/mm3 is associated with a number of immunological abnormalities, including a skewed T cell phenotype from naïve toward terminally differentiated CD8+ T cells, higher levels of CD8+ T cell activation (HLADR+CD38+ and senescence (CD28- and CD57+CD28-, and higher kynurenine/tryptophan ratio. Changes in the peripheral CD4/CD8 ratio are also reflective of changes in gut mucosa, but not in lymph nodes. In a longitudinal study, individuals who initiated ART within six months of infection had greater CD4/CD8 ratio increase compared to later initiators (>2 years. After controlling for age, gender, ART duration, nadir and CD4 count, the CD4/CD8 ratio predicted increased risk of morbidity and mortality. Hence, a persistently low CD4/CD8 ratio during otherwise effective ART is associated with increased innate and adaptive immune activation, an immunosenescent phenotype, and higher risk of morbidity/mortality. This ratio may prove useful in monitoring response to ART and could identify a unique subset of individuals needed of novel therapeutic interventions.

  20. Mechanisms involved in alternariol-induced cell cycle arrest

    Energy Technology Data Exchange (ETDEWEB)

    Solhaug, A., E-mail: Anita.Solhaug@vetinst.no [Norwegian Veterinary Institute, Oslo (Norway); Vines, L.L. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Ivanova, L.; Spilsberg, B. [Norwegian Veterinary Institute, Oslo (Norway); Holme, J.A. [Norwegian Institute of Public Health, Division of Environmental Medicine, Oslo (Norway); Pestka, J. [Michigan State University, Department of Food Science and Human Nutrition, East Lansing, MI (United States); Collins, A. [University of Oslo, Department of Nutrition, Faculty of Medicine, Oslo (Norway); Eriksen, G.S. [Norwegian Veterinary Institute, Oslo (Norway)

    2012-10-15

    Alternariol (AOH), a mycotoxin produced by Alternaria sp, is often found as a contaminant in fruit and cereal products. Here we employed the murine macrophage cell line RAW 264.7 to test the hypothesis that AOH causes toxicity as a response to DNA damage. AOH at concentrations of 15-30 {mu}M almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 {mu}M) significantly increased the level of reactive oxygen species (ROS). Furthermore, DNA base oxidations as well as DNA strand breaks and/or alkaline labile sites were detected by the comet assay after 2 h exposure of AOH. Cell death (mostly necrosis) was observed after prolonged exposure to the highest concentration of AOH (60 {mu}M for 24 and 48 h) in our study. The DNA damage response involved phosphorylation (activation) of histone H2AX and check point kinase-1- and 2 (Chk-1/2). Moreover, AOH activated p53 and increased the expression of p21, Cyclin B, MDM2, and Sestrin 2; likewise the level of several miRNA was affected. AOH-induced Sestrin 2 expression was regulated by p53 and could at least partly be inhibited by antioxidants, suggesting a role of ROS in the response. Interestingly, the addition of antioxidants did not inhibit cell cycle arrest. Although the formation of ROS by itself was not directly linked cell proliferation, AOH-induced DNA damage and resulting transcriptional changes in p21, MDM2, and Cyclin B likely contribute to the reduced cell proliferation; while Sestrin 2 would contribute to the oxidant defense.

  1. 树突状细胞亚群与肿瘤免疫治疗%Dendritic Cell Subsets and Tumor Immunotherapy

    Institute of Scientific and Technical Information of China (English)

    田丰; 周凯(综述); 王龙信(审校)

    2015-01-01

    Dendritic cells(DC) play a key role in the induction and regulation of immune responses, including the activation of cytotoxic T lymphocytes for the eradication of cancers .DC-based cancer vaccines can be tolerated,with few side effects and can induce anti-tumor immune responses,but the overall effects are limited.Recent studies showed that CD141 +DC play an important role in anti-tumor responses.These are now novel targets for the development of vaccines that directly target DC in vivo .With the deepening of the under-standing of the specialized functions of DC subsets,strategies for the delivery of tumor Ag to DC,a promising new direction for the design of more effective DC-based cancer vaccines is pointed out.%树突状细胞( DC)在诱导和调节免疫反应中起关键作用,包括激活消除肿瘤细胞的细胞毒性T淋巴细胞。以DC为基础的肿瘤疫苗能够被机体耐受、很少有不良反应,同时又能诱导抗肿瘤的免疫反应,但是其效果有限。研究表明,DC具有多种表型,CD141+DC 在抗肿瘤反应中扮演着重要的角色。这成为DC疫苗在体内应用发展的新方向。对不同 DC 亚群特殊功能的深入了解,以及对肿瘤抗原负载新方法的研究,为设计出更有效的DC肿瘤疫苗指出了一条更有希望的道路。

  2. Cestodiasis tisulares: participación de los linfocitos T cooperadores 1 y 2 Tisular cestodiasis: The role of T helper cell subsets 1 and 2

    Directory of Open Access Journals (Sweden)

    Héctor Samuel López-Moreno

    2002-04-01

    Full Text Available La cisticercosis y la hidatidosis son las parasitosis causadas por los metacéstodos de Taenia solium y de Echinococcus multilocularis (o E. granulosus, respectivamente. El estudio de las enfermedades parasitarias ofrece uno de los mejores modelos in vivo para el estudio de la división efectora de las subpoblaciones de linfocitos T cooperadores CD4+, designadas Th1 y Th2 de acuerdo con el patrón de citocinas que producen. La polarización hacia alguno de estos fenotipos puede marcar la diferencia entre una respuesta inmune celular protectora o una respuesta inmune permisiva para la infección. La participación de los linfocitos Th1 y Th2 en las cestodiasis tisulares (cisticercosis e hidatidosis ha sido estudiada en modelos experimentales de ratón y en pacientes humanos; en ambos casos los resultados sugieren que en los individuos con cisticercosis o hidatidosis la respuesta inmune celular está polarizada hacia un fenotipo Th2. En tanto que en los individuos donde los parásitos son destruidos, o su desarrollo está limitado, la respuesta inmune celular se encuentra polarizada hacia un fenotipo Th1.Cysticercosis and hydatidosis are parasitic diseases caused by larvae of Taenia solium and Echinococcus sp., respectively. Parasitic diseases are useful models for in vivo studies of effector functions of T helper cell subsets 1 and 2, (called Th1 and Th2 on the basis of the pattern of cytokines they produce. The polarization to Th1 or Th2 is related to protective or permissive immune responses in these diseases. The role of Th1 and Th2 lymphocytes in tissue cestodiasis (cysticercosis and hydatidosis has been studied in experimentally infected mice and in human patients; study results suggest that in individuals with cysticercosis or hydatidosis, the cellular immune response is polarized to Th2, while individuals in whom parasites are killed or their growth is limited, have an immune cellular response that is polarized towards Th1.

  3. CD4+ Th17 Cells Discriminate Clinical Types and Constitute a Third Subset of Non Th1, Non Th2 T Cells in Human Leprosy

    Science.gov (United States)

    Saini, Chaman; Ramesh, V.; Nath, Indira

    2013-01-01

    Background Patients with localized tuberculoid and generalized lepromatous leprosy show respectively Th1 and Th2 cytokine profile. Additionally, other patients in both types of leprosy also show a non discriminating Th0 cytokine profile with both interferon-γ and IL-4. The present study investigated the role of Th17 cells which appear to be a distinct subtype of Th subtypes in 19 tuberculoid and 18 lepromatous leprosy patients. Five healthy subjects with long term exposure to infection and 4 skin biopsies from healthy subjects undergoing cosmetic surgery were used as controls. Methodology/Principle Findings An array of Th17 related primers for cytokines, chemokines and transcription factors was used in real time reverse transcribed PCR to evaluate gene expression, ELISA for cytokine secretion in the supernatants of antigen stimulated PBMC cultures and flow cytometry for establishing the phenotype of the IL-17, IL-21 producing cells. Conclusions/Significance IL-17 isoforms showed significantly higher expression and release in supernatants of antigen stimulated PBMC cultures and dermal lesions of healthy contacts and tuberculoid leprosy as compared to lepromatous leprosy (p<0.003). This was further confirmed by Th17 associated transcription factor RORC, cytokines IL-21, IL-22, and IL-23, chemokines MMP13, CCL20, CCL22. Of interest was the association of IL-23R and not IL-6R with IL-17+ cells. The Th17 cells were CD4+ CCR6+ confirming their effector cell lineage. Polarized Th1 cytokines were seen in 3/7 tuberculoid and Th2 cytokines in 5/10 lepromatous leprosy patients. Of importance was the higher association of Th17 pathway factors with the non-polarized Th0 types as compared to the polarized Th1 and Th2 (p<0.01). Our study draws attention to a third type of effector Th cell that may play a role in leprosy. PMID:23936569

  4. CD4+ Th17 cells discriminate clinical types and constitute a third subset of non Th1, Non Th2 T cells in human leprosy.

    Directory of Open Access Journals (Sweden)

    Chaman Saini

    Full Text Available BACKGROUND: Patients with localized tuberculoid and generalized lepromatous leprosy show respectively Th1 and Th2 cytokine profile. Additionally, other patients in both types of leprosy also show a non discriminating Th0 cytokine profile with both interferon-γ and IL-4. The present study investigated the role of Th17 cells which appear to be a distinct subtype of Th subtypes in 19 tuberculoid and 18 lepromatous leprosy patients. Five healthy subjects with long term exposure to infection and 4 skin biopsies from healthy subjects undergoing cosmetic surgery were used as controls. METHODOLOGY/PRINCIPLE FINDINGS: An array of Th17 related primers for cytokines, chemokines and transcription factors was used in real time reverse transcribed PCR to evaluate gene expression, ELISA for cytokine secretion in the supernatants of antigen stimulated PBMC cultures and flow cytometry for establishing the phenotype of the IL-17, IL-21 producing cells. CONCLUSIONS/SIGNIFICANCE: IL-17 isoforms showed significantly higher expression and release in supernatants of antigen stimulated PBMC cultures and dermal lesions of healthy contacts and tuberculoid leprosy as compared to lepromatous leprosy (p<0.003. This was further confirmed by Th17 associated transcription factor RORC, cytokines IL-21, IL-22, and IL-23, chemokines MMP13, CCL20, CCL22. Of interest was the association of IL-23R and not IL-6R with IL-17(+ cells. The Th17 cells were CD4(+ CCR6(+ confirming their effector cell lineage. Polarized Th1 cytokines were seen in 3/7 tuberculoid and Th2 cytokines in 5/10 lepromatous leprosy patients. Of importance was the higher association of Th17 pathway factors with the non-polarized Th0 types as compared to the polarized Th1 and Th2 (p<0.01. Our study draws attention to a third type of effector Th cell that may play a role in leprosy.

  5. PD-1 Expression and Cytokine Secretion Profiles of Mycobacterium tuberculosis-Specific CD4+ T-Cell Subsets; Potential Correlates of Containment in HIV-TB Co-Infection.

    Directory of Open Access Journals (Sweden)

    Katrina M Pollock

    Full Text Available HIV co-infection is an important risk factor for tuberculosis (TB providing a powerful model in which to dissect out defective, protective and dysfunctional Mycobacterium tuberculosis (MTB-specific immune responses. To identify the changes induced by HIV co-infection we compared MTB-specific CD4+ responses in subjects with active TB and latent TB infection (LTBI, with and without HIV co-infection. CD4+ T-cell subsets producing interferon-gamma (IFN-γ, interleukin-2 (IL-2 and tumour necrosis factor-alpha (TNF-α and expressing CD279 (PD-1 were measured using polychromatic flow-cytometry. HIV-TB co-infection was consistently and independently associated with a reduced frequency of CD4+ IFN-γ and IL-2-dual secreting T-cells and the proportion correlated inversely with HIV viral load (VL. The impact of HIV co-infection on this key MTB-specific T-cell subset identifies them as a potential correlate of mycobacterial immune containment. The percentage of MTB-specific IFN-γ-secreting T-cell subsets that expressed PD-1 was increased in active TB with HIV co-infection and correlated with VL. This identifies a novel correlate of dysregulated immunity to MTB, which may in part explain the paucity of inflammatory response in the face of mycobacterial dissemination that characterizes active TB with HIV co-infection.

  6. PD-1 Expression and Cytokine Secretion Profiles of Mycobacterium tuberculosis-Specific CD4+ T-Cell Subsets; Potential Correlates of Containment in HIV-TB Co-Infection.

    Science.gov (United States)

    Pollock, Katrina M; Montamat-Sicotte, Damien J; Grass, Lisa; Cooke, Graham S; Kapembwa, Moses S; Kon, Onn M; Sampson, Robert D; Taylor, Graham P; Lalvani, Ajit

    2016-01-01

    HIV co-infection is an important risk factor for tuberculosis (TB) providing a powerful model in which to dissect out defective, protective and dysfunctional Mycobacterium tuberculosis (MTB)-specific immune responses. To identify the changes induced by HIV co-infection we compared MTB-specific CD4+ responses in subjects with active TB and latent TB infection (LTBI), with and without HIV co-infection. CD4+ T-cell subsets producing interferon-gamma (IFN-γ), interleukin-2 (IL-2) and tumour necrosis factor-alpha (TNF-α) and expressing CD279 (PD-1) were measured using polychromatic flow-cytometry. HIV-TB co-infection was consistently and independently associated with a reduced frequency of CD4+ IFN-γ and IL-2-dual secreting T-cells and the proportion correlated inversely with HIV viral load (VL). The impact of HIV co-infection on this key MTB-specific T-cell subset identifies them as a potential correlate of mycobacterial immune containment. The percentage of MTB-specific IFN-γ-secreting T-cell subsets that expressed PD-1 was increased in active TB with HIV co-infection and correlated with VL. This identifies a novel correlate of dysregulated immunity to MTB, which may in part explain the paucity of inflammatory response in the face of mycobacterial dissemination that characterizes active TB with HIV co-infection.

  7. Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation

    DEFF Research Database (Denmark)

    Magnusson, M. K.; Brynjólfsson, S. F.; Dige, A.;

    2016-01-01

    Disruption of the homeostatic balance of intestinal dendritic cells (DCs) and macrophages (MQs) may contribute to inflammatory bowel disease. We characterized DC and MQ populations, including their ability to produce retinoic acid, in clinical material encompassing Crohn’s ileitis, Crohn’s coliti...

  8. Loss of post-transcriptional regulation of DNMT3b by microRNAs: a possible molecular mechanism for the hypermethylation defect observed in a subset of breast cancer cell lines.

    Science.gov (United States)

    Sandhu, Rupninder; Rivenbark, Ashley G; Coleman, William B

    2012-08-01

    A hypermethylation defect associated with DNMT hyperactivity and DNMT3b overexpression characterizes a subset of breast cancers and breast cancer cell lines. We analyzed breast cancer cell lines for differential expression of regulatory miRs to determine if loss of miR-mediated post-transcriptional regulation of DNMT3b represents the molecular mechanism that governs the overexpression of DNMT3b that drives the hypermethylation defect in breast cancer. MicroRNAs (miRs) that regulate (miR-29a, miR-29b, miR-29c, miR-148a, miR-148b) or are predicted (miR-26a, miR-26b, miR-203, miR-222) to regulate DNMT3b were examined among 10 hypermethylator and 6 non-hypermethylator breast cancer cell lines. Hypermethylator cell lines express diminished levels of miR-29c, miR-148a, miR-148b, miR-26a, miR-26b, and miR-203 compared to non-hypermethylator cell lines. miR expression patterns correlate inversely with methylation-sensitive gene expression (r=-0.66, p=0.0056) and directly with the methylation status of these genes (r=0.72, p=0.002). To determine the mechanistic role of specific miRs in the dysregulation of DNMT3b among breast cancer cell lines, miR levels were modulated by transfection of pre-miR precursors for miR-148b, miR-26b, and miR-29c into hypermethylator cell lines (Hs578T, HCC1937, SUM185) and transfection of antagomirs directed against miR-148b, miR-26b, and miR-29c into non-hypermethylator cell lines (BT20, MDA-MB-415, MDA-MB-468). Antagomir-mediated knock-down of miR-148b, miR-29c, and miR-26b significantly increased DNMT3b mRNA in non-hypermethylator cell lines, and re-expression of miR-148b, miR-29c, and miR-26b following transfection of pre-miR precursors significantly reduced DNMT3b mRNA in hypermethylator cell lines. These findings strongly suggest that: i) post-transcriptional regulation of DNMT3b is combinatorial, ii) diminished expression of regulatory miRs contributes to DNMT3b overexpression, iii) re-expression of regulatory miRs reduces DNMT3b m

  9. Intratumoural and peripheral blood lymphocyte subsets in patients with metastatic renal cell carcinoma undergoing interleukin-2 based immunotherapy: association to objective response and survival

    DEFF Research Database (Denmark)

    Donskov, F; Bennedsgaard, K M; Von Der Maase, H

    2002-01-01

    The aim of the present study was to analyse lymphocyte subsets in consecutive peripheral blood samples and consecutive tumour tissue core needle biopsies performed before and during interleukin-2 based immunotherapy, and to correlate the findings with objective response and survival. Twenty...... response or survival. Within the tumour tissue at baseline, a significant positive correlation between CD4 (P=0.027), CD8 (P=0.028), CD57 (P=0.007) and objective response was demonstrated. After one month of immunotherapy, a significant positive correlation between intratumoral CD3 (P=0.026), CD8 (P=0...... of lymphocyte subsets in the tumour reduction in responding patients during interleukin-2 based immunotherapy. Confirmation of the results requires further studies including a larger number of patients....

  10. Multifocal Extranodal Involvement of Diffuse Large B-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Devrim Cabuk

    2013-01-01

    Full Text Available Endobronchial involvement of extrapulmonary malignant tumors is uncommon and mostly associated with breast, kidney, colon, and rectum carcinomas. A 68-year-old male with a prior diagnosis of colon non-Hodgkin lymphoma (NHL was admitted to the hospital with a complaint of cough, sputum, and dyspnea. The chest radiograph showed right hilar enlargement and opacity at the right middle zone suggestive of a mass lesion. Computed tomography of thorax revealed a right-sided mass lesion extending to thoracic wall with the destruction of the third and the fourth ribs and a right hilar mass lesion. Fiberoptic bronchoscopy was performed in order to evaluate endobronchial involvement and showed stenosis with mucosal tumor infiltration in right upper lobe bronchus. The pathological examination of bronchoscopic biopsy specimen reported diffuse large B-cell lymphoma and the patient was accepted as the endobronchial recurrence of sigmoid colon NHL. The patient is still under treatment of R-ICE (rituximab-ifosfamide-carboplatin-etoposide chemotherapy and partial regression of pulmonary lesions was noted after 3 courses of treatment.

  11. Expression of Th17 and Treg lymphocyte subsets in hypertrophied adenoids of children and its clinical significance.

    Science.gov (United States)

    Sade, Kobi; Fishman, Gadi; Kivity, Shmuel; DeRowe, Ari; Langier, Sheila

    2011-01-01

    Adenoid hypertrophy is the most common cause of upper airway obstruction and sleep-disordered breathing in children, yet its pathogenesis remains unclear. The identification of the novel helper T cell subsets, Th17 cells and regulatory T cells (Tregs) could provide new insight into our understanding of the mechanisms involved in the development of this condition. The purpose of this study is to evaluate the adenoidal lymphocyte subsets to describe the percentage of various lymphocyte subsets in hypertrophied adenoids and correlate them with symptom severity. Twenty consecutive children undergoing adenoidectomy were included, and lymphocytes were isolated from their adenoids. T cell subpopulations were detected by flow cytometry using a fluoresceinated monoclonal antibody directed against a number of cell markers (CD4+, CD8+, CD25+, FOXP3 IL17+, and others). We found a significant negative linear correlation between the Th17/Treg ratio and the patients' clinical scores (R = -0.71 p adenoid hypertrophy.

  12. Voltage-gated sodium channel Nav1.7 maintains the membrane potential and regulates the activation and chemokine-induced migration of a monocyte-derived dendritic cell subset.

    Science.gov (United States)

    Kis-Toth, Katalin; Hajdu, Peter; Bacskai, Ildiko; Szilagyi, Orsolya; Papp, Ferenc; Szanto, Attila; Posta, Edit; Gogolak, Peter; Panyi, Gyorgy; Rajnavolgyi, Eva

    2011-08-01

    Expression of CD1a protein defines a human dendritic cell (DC) subset with unique functional activities. We aimed to study the expression of the Nav1.7 sodium channel and the functional consequences of its activity in CD1a(-) and CD1a(+) DC. Single-cell electrophysiology (patch-clamp) and quantitative PCR experiments performed on sorted CD1a(-) and CD1a(+) immature DC (IDC) showed that the frequency of cells expressing Na(+) current, current density, and the relative expression of the SCN9A gene encoding Nav1.7 were significantly higher in CD1a(+) cells than in their CD1a(-) counterparts. The activity of Nav1.7 results in a depolarized resting membrane potential (-8.7 ± 1.5 mV) in CD1a(+) IDC as compared with CD1a(-) cells lacking Nav1.7 (-47 ± 6.2 mV). Stimulation of DC by inflammatory signals or by increased intracellular Ca(2+) levels resulted in reduced Nav1.7 expression. Silencing of the SCN9A gene shifted the membrane potential to a hyperpolarizing direction in CD1a(+) IDC, resulting in decreased cell migration, whereas pharmacological inhibition of Nav1.7 by tetrodotoxin sensitized the cells for activation signals. Fine-tuning of IDC functions by a voltage-gated sodium channel emerges as a new regulatory mechanism modulating the migration and cytokine responses of these DC subsets.

  13. Acinar Cell Carcinoma of the Pancreas with Colon Involvement

    Directory of Open Access Journals (Sweden)

    Naoki Asayama

    2014-01-01

    Full Text Available We report a case of acinar cell carcinoma of the pancreas with colon involvement that was difficult to distinguish from primary colon cancer. A 60-year-old man was admitted with a 1-month history of diarrhea. Contrast-enhanced computed tomography (CT revealed a large tumor (10.6×11.6 cm at the splenic flexure of the colon. Colonoscopy showed completely round ulcerative lesions, and biopsy revealed poorly differentiated adenocarcinoma. Left hemicolectomy, resection of the jejunum and pancreas body and tail, and splenectomy were performed based on a diagnosis of descending colon cancer (cT4N0M0, stage IIB, and surgery was considered to be curative. Diagnosis was subsequently confirmed as moderately differentiated acinar cell carcinoma of the pancreas by immunohistochemical staining (pT3N0M0, stage IIA. Multiple liver metastases with portal thrombosis were found 8 weeks postoperatively. Despite combination chemotherapy with oral S-1 and gemcitabine, the patient died of hepatic failure with no effect of chemotherapy 14 weeks postoperatively. Correct diagnosis was difficult to determine preoperatively from the clinical, CT, and colonoscopy findings. Moreover, the disease was extremely aggressive even after curative resection. Physicians should consider pancreatic cancer in the differential diagnosis of similar cases.

  14. Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death.

    Science.gov (United States)

    Laborde, E

    2010-09-01

    Glutathione transferases (GSTs) are enzymes that catalyze the conjugation of glutathione (GSH) to a variety of electrophilic substances. Their best known role is as cell housekeepers engaged in the detoxification of xenobiotics. Recently, GSTs have also been shown to act as modulators of signal transduction pathways that control cell proliferation and cell death. Their involvement in cancer cell growth and differentiation, and in the development of resistance to anticancer agents, has made them attractive drug targets. This review is focused on the inhibition of GSTs, in particular GSTP1-1, as a potential therapeutic approach for the treatment of cancer and other diseases associated with aberrant cell proliferation.

  15. Live-cell monitoring of periodic gene expression in synchronous human cells identifies Forkhead genes involved in cell cycle control.

    Science.gov (United States)

    Grant, Gavin D; Gamsby, Joshua; Martyanov, Viktor; Brooks, Lionel; George, Lacy K; Mahoney, J Matthew; Loros, Jennifer J; Dunlap, Jay C; Whitfield, Michael L

    2012-08-01

    We developed a system to monitor periodic luciferase activity from cell cycle-regulated promoters in synchronous cells. Reporters were driven by a minimal human E2F1 promoter with peak expression in G1/S or a basal promoter with six Forkhead DNA-binding sites with peak expression at G2/M. After cell cycle synchronization, luciferase activity was measured in live cells at 10-min intervals across three to four synchronous cell cycles, allowing unprecedented resolution of cell cycle-regulated gene expression. We used this assay to screen Forkhead transcription factors for control of periodic gene expression. We confirmed a role for FOXM1 and identified two novel cell cycle regulators, FOXJ3 and FOXK1. Knockdown of FOXJ3 and FOXK1 eliminated cell cycle-dependent oscillations and resulted in decreased cell proliferation rates. Analysis of genes regulated by FOXJ3 and FOXK1 showed that FOXJ3 may regulate a network of zinc finger proteins and that FOXK1 binds to the promoter and regulates DHFR, TYMS, GSDMD, and the E2F binding partner TFDP1. Chromatin immunoprecipitation followed by high-throughput sequencing analysis identified 4329 genomic loci bound by FOXK1, 83% of which contained a FOXK1-binding motif. We verified that a subset of these loci are activated by wild-type FOXK1 but not by a FOXK1 (H355A) DNA-binding mutant.

  16. The bacterial cell cycle regulator GcrA is a σ70 cofactor that drives gene expression from a subset of methylated promoters.

    Science.gov (United States)

    Haakonsen, Diane L; Yuan, Andy H; Laub, Michael T

    2015-11-01

    Cell cycle progression in most organisms requires tightly regulated programs of gene expression. The transcription factors involved typically stimulate gene expression by binding specific DNA sequences in promoters and recruiting RNA polymerase. Here, we found that the essential cell cycle regulator GcrA in Caulobacter crescentus activates the transcription of target genes in a fundamentally different manner. GcrA forms a stable complex with RNA polymerase and localizes to almost all active σ(70)-dependent promoters in vivo but activates transcription primarily at promoters harboring certain DNA methylation sites. Whereas most transcription factors that contact σ(70) interact with domain 4, GcrA interfaces with domain 2, the region that binds the -10 element during strand separation. Using kinetic analyses and a reconstituted in vitro transcription assay, we demonstrated that GcrA can stabilize RNA polymerase binding and directly stimulate open complex formation to activate transcription. Guided by these studies, we identified a regulon of ∼ 200 genes, providing new insight into the essential functions of GcrA. Collectively, our work reveals a new mechanism for transcriptional regulation, and we discuss the potential benefits of activating transcription by promoting RNA polymerase isomerization rather than recruitment exclusively.

  17. T-lymphocyte subsets in recurrent aphthous ulceration

    DEFF Research Database (Denmark)

    Pedersen, A; Klausen, B; Hougen, H P;

    1989-01-01

    Peripheral T-lymphocyte subsets: T-helper (OKT4) and T-suppressor (OKT8) cells were studied quantitatively in 20 patients with recurrent aphthous ulceration (RAU) in ulcerative, as well as inactive, stages of the disease. The figures were compared with T-lymphocyte subsets from matched control do...

  18. Systemic inflammation in progressive multiple sclerosis involves follicular T-helper, Th17- and activated B-cells and correlates with progression.

    Directory of Open Access Journals (Sweden)

    Jeppe Romme Christensen

    Full Text Available Pathology studies of progressive multiple sclerosis (MS indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH cells. Although previous studies reported increased systemic inflammation in progressive MS it remains unclear whether systemic inflammation contributes to disease progression and intrathecal inflammation. This study aimed to investigate systemic inflammation in progressive MS and its relationship with disease progression, using flow cytometry and gene expression analysis of CD4(+ and CD8(+T-cells, B-cells, monocytes and dendritic cells. Furthermore, gene expression of cerebrospinal fluid cells was studied. Flow cytometry studies revealed increased frequencies of ICOS(+TFH-cells in peripheral blood from relapsing-remitting (RRMS and secondary progressive (SPMS MS patients. All MS subtypes had decreased frequencies of Th1 TFH-cells, while primary progressive (PPMS MS patients had increased frequency of Th17 TFH-cells. The Th17-subset, interleukin-23-receptor(+CD4(+T-cells, was significantly increased in PPMS and SPMS. In the analysis of B-cells, we found a significant increase of plasmablasts and DC-SIGN(+ and CD83(+B-cells in SPMS. ICOS(+TFH-cells and DC-SIGN(+B-cells correlated with disease progression in SPMS patients. Gene expression analysis of peripheral blood cell subsets substantiated the flow cytometry findings by demonstrating increased expression of IL21, IL21R and ICOS in CD4(+T-cells in progressive MS. Cerebrospinal fluid cells from RRMS and progressive MS (pooled SPMS and PPMS patients had increased expression of TFH-cell and plasmablast markers. In conclusion, this study is the first to demonstrate the potential involvement of activated TFH-cells in MS. The increased frequencies of Th17-cells, activated TFH- and B-cells parallel findings

  19. Singular Features of Trypanosomatids' Phosphotransferases Involved in Cell Energy Management

    Directory of Open Access Journals (Sweden)

    Claudio A. Pereira

    2011-01-01

    Full Text Available Trypanosomatids are responsible for economically important veterinary affections and severe human diseases. In Africa, Trypanosoma brucei causes sleeping sickness or African trypanosomiasis, while in America, Trypanosoma cruzi is the etiological agent of Chagas disease. These parasites have complex life cycles which involve a wide variety of environments with very different compositions, physicochemical properties, and availability of metabolites. As the environment changes there is a need to maintain the nucleoside homeostasis, requiring a quick and regulated response. Most of the enzymes required for energy management are phosphotransferases. These enzymes present a nitrogenous group or a phosphate as acceptors, and the most clear examples are arginine kinase, nucleoside diphosphate kinase, and adenylate kinase. Trypanosoma and Leishmania have the largest number of phosphotransferase isoforms ever found in a single cell; some of them are absent in mammals, suggesting that these enzymes are required in many cellular compartments associated to different biological processes. The presence of such number of phosphotransferases support the hypothesis of the existence of an intracellular enzymatic phosphotransfer network that communicates the spatially separated intracellular ATP consumption and production processes. All these unique features make phosphotransferases a promising start point for rational drug design for the treatment of human trypanosomiasis.

  20. Involvement of plant stem cells or stem cell-like cells in dedifferentiation

    Directory of Open Access Journals (Sweden)

    Fangwei eJiang

    2015-11-01

    Full Text Available Dedifferentiation is the transformation of cells from a given differentiated state to a less differentiated or stem cell-like state. Stem cell-related genes play important roles in dedifferentiation, which exhibits similar histone modification and DNA methylation features to stem cell maintenance. Hence, stem cell-related factors possibly synergistically function to provide a specific niche beneficial to dedifferentiation. During callus formation in Arabidopsis petioles, cells adjacent to procambium cells (stem cell-like cells are dedifferentiated and survive more easily than other cell types. This finding indicates that stem cells or stem cell-like cells may influence the dedifferentiating niche. In this paper, we provide a brief overview of stem cell maintenance and dedifferentiation regulation. We also summarize current knowledge of genetic and epigenetic mechanisms underlying the balance between differentiation and dedifferentiation. Furthermore, we discuss the correlation of stem cells or stem cell-like cells with dedifferentiation.

  1. DMPD: Signals and receptors involved in recruitment of inflammatory cells. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 7744810 Signals and receptors involved in recruitment of inflammatory cells. Ben-Ba...ow Signals and receptors involved in recruitment of inflammatory cells. PubmedID 7744810 Title Signals and r...eceptors involved in recruitment of inflammatory cells. Authors Ben-Baruch A, Mic

  2. Product-free subsets of profinite groups

    CERN Document Server

    Bardestani, Mohammad

    2012-01-01

    Gowers in his paper on quasirandom groups studies a question of Babai and Sos asking whether there exists a constant $c > 0$ such that every finite group $G$ has a product-free subset of size at least $c|G|$. Answering the question negatively, he proves that for sufficiently large prime $p$, the group $\\mathrm{PSL}_2(\\mathbb{F}_p)$ has no product-free subset of size $cn^{8/9}$, where $n$ is the order of $\\mathrm{PSL}_2(\\mathbb{F}_p)$. We will consider the problem for compact groups and in particular for profinite groups $\\SL_k(\\ZZ_p)$ obtain lower and upper exponential bounds for the supremal measure of the product-free sets. The proof involves establishing a lower bound for the dimension of non-trivial representations of the finite groups $\\SL_k(\\Z{p^n})$.

  3. Alpha-interferon induces enhanced expression of HLA-ABC antigens and beta-2-microglobulin in vivo and in vitro in various subsets of human lymphoid cells

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Larsen, J K; Plesner, T;

    1987-01-01

    The effect of cloned alpha-interferon (alpha-IFN) on the in vitro and in vivo expression of HLA-ABC antigens and beta-2-microglobulin (beta-2-m) on subpopulations of human lymphoid cells was studied by flow cytometry. Mononuclear cells isolated from patients and cell cultures were labelled...

  4. A subset of μ-opioid receptor-expressing cells in the rostral ventromedial medulla contribute to thermal hyperalgesia in experimental neuropathic pain.

    Science.gov (United States)

    Mase, Hiroshi; Sakai, Atsushi; Sakamoto, Atsuhiro; Suzuki, Hidenori

    2011-05-01

    The rostral ventromedial medulla (RVM) is a major region for the descending modulation of pain at the spinal cord level, and neurons in the RVM have been implicated in the inhibition and facilitation of spinal nociceptive transmission. Although recent studies have established that the RVM facilitation of nociceptive transmission in the spinal cord contributes to neuropathic pain, the underlying mechanisms remain largely unknown. In the present study, we investigated the effects of kainic acid (KA)-induced RVM damage on neuropathic pain behavior and the expression of molecules implicated in pain modulation. KA was injected into the RVM midline region after neuropathic pain was established by chronic constrictive injury of the left sciatic nerve. Thermal hyperalgesia, but not mechanical allodynia, was persistently suppressed in the ipsilateral paw by a single KA injection into the RVM for at least the next 7 days in a rat neuropathic pain model. KA injection alone did not affect the nocifensive responses to mechanical and thermal stimuli on the intact side. Immunohistochemical analysis revealed that KA injection into the RVM significantly reduced the number of immunoreactive neurons for μ-opioid receptors, but not tryptophan hydroxylase, in association with the analgesic effect. These results suggest that a subset of RVM neurons expressing μ-opioid receptors contribute to the maintenance of thermal hyperalgesia in neuropathic pain.

  5. Involvement of mast cells in adipose tissue fibrosis.

    Science.gov (United States)

    Hirai, Shizuka; Ohyane, Chie; Kim, Young-Il; Lin, Shan; Goto, Tsuyoshi; Takahashi, Nobuyuki; Kim, Chu-Sook; Kang, Jihey; Yu, Rina; Kawada, Teruo

    2014-02-01

    Recently, fibrosis is observed in obese adipose tissue; however, the pathogenesis remains to be clarified. Obese adipose tissue is characterized by chronic inflammation with massive accumulation of immune cells including mast cells. The objective of the present study was to clarify the relationship between fibrosis and mast cells in obese adipose tissue, as well as to determine the origin of infiltrating mast cells. We observed the enhancement of mast cell accumulation and fibrosis in adipose tissue of severely obese diabetic db/db mice. Furthermore, adipose tissue-conditioned medium (ATCM) from severely obese diabetic db/db mice significantly enhanced collagen 5 mRNA expression in NIH-3T3 fibroblasts, and this enhancement was suppressed by the addition of an anti-mast cell protease 6 (MCP-6) antibody. An in vitro study showed that only collagen V among various types of collagen inhibited preadipocyte differentiation. Moreover, we found that ATCM from the nonobese but not obese stages of db/db mice significantly enhanced the migration of bone marrow-derived mast cells (BMMCs). These findings suggest that immature mast cells that infiltrate into adipose tissue at the nonobese stage gradually mature with the progression of obesity and diabetes and that MCP-6 secreted from mature mast cells induces collagen V expression in obese adipose tissue, which may contribute to the process of adipose tissue fibrosis. Induction of collagen V by MCP-6 might accelerate insulin resistance via the suppression of preadipocyte differentiation.

  6. ROCK2 signaling is required to induce a subset of T follicular helper cells through opposing effects on STATs in autoimmune settings.

    Science.gov (United States)

    Weiss, Jonathan M; Chen, Wei; Nyuydzefe, Melanie S; Trzeciak, Alissa; Flynn, Ryan; Tonra, James R; Marusic, Suzana; Blazar, Bruce R; Waksal, Samuel D; Zanin-Zhorov, Alexandra

    2016-07-19

    Rho-associated kinase 2 (ROCK2) determines the balance between human T helper 17 (TH17) cells and regulatory T (Treg) cells. We investigated its role in the generation of T follicular helper (TFH) cells, which help to generate antibody-producing B cells under normal and autoimmune conditions. Inhibiting ROCK2 in normal human T cells or peripheral blood mononuclear cells from patients with active systemic lupus erythematosus (SLE) decreased the number and function of TFH cells induced by activation ex vivo. Moreover, inhibition of ROCK2 activity decreased the abundance of the transcriptional regulator Bcl6 (B cell lymphoma 6) and increased that of Blimp1 by reducing the binding of signal transducer and activator of transcription 3 (STAT3) and increasing that of STAT5 to the promoters of the genes Bcl6 and PRDM1, respectively. In the MRL/lpr murine model of SLE, oral administration of the selective ROCK2 inhibitor KD025 resulted in a twofold reduction in the numbers of TFH cells and antibody-producing plasma cells in the spleen, as well as a decrease in the size of splenic germinal centers, which are the sites of interaction between TFH cells and B cells. KD025-treated mice showed a substantial improvement in both histological and clinical scores compared to those of untreated mice and had reduced amounts of Bcl6 and phosphorylated STAT3, as well as increased STAT5 phosphorylation. Together, these data suggest that ROCK2 signaling plays a critical role in controlling the development of TFH cells induced by autoimmune conditions through reciprocal regulation of STAT3 and STAT5 activation.

  7. Induction of Apoptosis by Luteolin Involving Akt Inactivation in Human 786-O Renal Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Yen-Chuan Ou

    2013-01-01

    Full Text Available There is a growing interest in the health-promoting effects of natural substances obtained from plants. Although luteolin has been identified as a potential therapeutic and preventive agent for cancer because of its potent cancer cell-killing activity, the molecular mechanisms have not been well elucidated. This study provides evidence of an alternative target for luteolin and sheds light on the mechanism of its physiological benefits. Treatment of 786-O renal cell carcinoma (RCC cells (as well as A498 and ACHN with luteolin caused cell apoptosis and death. This cytotoxicity was caused by the downregulation of Akt and resultant upregulation of apoptosis signal-regulating kinase-1 (Ask1, p38, and c-Jun N-terminal kinase (JNK activities, probably via protein phosphatase 2A (PP2A activation. In addition to being a concurrent substrate of caspases and event of cell death, heat shock protein-90 (HSP90 cleavage might also play a role in driving further cellular alterations and cell death, at least in part, involving an Akt-related mechanism. Due to the high expression of HSP90 and Akt-related molecules in RCC and other cancer cells, our findings suggest that PP2A activation might work in concert with HSP90 cleavage to inactivate Akt and lead to a vicious caspase-dependent apoptotic cycle in luteolin-treated 786-O cells.

  8. Transcriptional activation of prostate specific homeobox gene NKX3-1 in subsets of T-cell lymphoblastic leukemia (T-ALL.

    Directory of Open Access Journals (Sweden)

    Stefan Nagel

    Full Text Available Homeobox genes encode transcription factors impacting key developmental processes including embryogenesis, organogenesis, and cell differentiation. Reflecting their tight transcriptional control, homeobox genes are often embedded in large non-coding, cis-regulatory regions, containing tissue specific elements. In T-cell acute lymphoblastic leukemia (T-ALL homeobox genes are frequently deregulated by chromosomal aberrations, notably translocations adding T-cell specific activatory elements. NKX3-1 is a prostate specific homeobox gene activated in T-ALL patients expressing oncogenic TAL1 or displaying immature T-cell characteristics. After investigating regulation of NKX3-1 in primary cells and cell lines, we report its ectopic expression in T-ALL cells independent of chromosomal rearrangements. Using siRNAs and expression profiling, we exploited NKX3-1 positive T-ALL cell lines as tools to investigate aberrant activatory mechanisms. Our data confirmed NKX3-1 activation by TAL1/GATA3/LMO and identified LYL1 as an alternative activator in immature T-ALL cells devoid of GATA3. Moreover, we showed that NKX3-1 is directly activated by early T-cell homeodomain factor MSX2. These activators were regulated by MLL and/or by IL7-, BMP4- and IGF2-signalling. Finally, we demonstrated homeobox gene SIX6 as a direct leukemic target of NKX3-1 in T-ALL. In conclusion, we identified three major mechanisms of NKX3-1 regulation in T-ALL cell lines which are represented by activators TAL1, LYL1 and MSX2, corresponding to particular T-ALL subtypes described in patients. These results may contribute to the understanding of leukemic transcriptional networks underlying disturbed T-cell differentiation in T-ALL.

  9. Change and significance of regulatory T cell subsets in patients with coronary artery disease%冠心病患者调节性T细胞亚群的变化及其意义

    Institute of Scientific and Technical Information of China (English)

    丁畅; 丁建东; 黄进; 陆治平; 王倩

    2013-01-01

    Objective To investigate the changes and significance of regulatory T cell subsets in the patients with coronary artery disease(CAD).Methods Sixty-one patients were divided into 3 groups of UA(21 cases with unstable angina),SA(18 cases with stable angina) and CPS(22 cases with chest pain syndrome).The frequencies of CD4+ CD25+ Foxp3+ regulatory T cell subsets in peripheral blood were detected by flow cytometry.Concentrations of transforming growth factor-β1 (TGF-β1) were measured by ELISA.Results The percentage of CD4+ CD25+ Foxp3+ regulatory T cell subsets in T lymphocytes in group UA was (1.89±0.76)%,which was significantly lower than (2.91±0.53)% in group SA and (2.35±0.26)% in group CPS(P<0.01).TGF-β1 expression in group UA was (13.52 ± 3.02) μg/L,which was significantly lower than (26.94 ± 7.25) μg/L in group SA and (25.93 ± 1.00) μg/L in group CPS(P<0.01).Conclusion The regulatory T cell subsets are downregulated in the patients with UA.The regulatory T cell subsets are closely associated with the activation of vulnerable atherosclerosis plaque.%目的 探讨冠心病患者外周血调节性T细胞(Treg细胞)亚群的变化及其意义.方法 将61例患者分为不稳定型心绞痛(UA组,21例)、稳定型心绞痛(SA组,18例)和胸痛综合征(CPS 组,22例)三组.采用流式细胞仪分析CD4+ CD25+ Foxp3+ Treg细胞占T淋巴细胞的比例;ELISA 法检测血浆转化生长因子β1(TGF-β1)浓度.结果 UA组CD4+ CD25+ Foxp3+ Treg细胞表达为(1.89±0.76)%,显著低于SA组的(2.91±0.53)%和CPS组的(2.35±0.26)% (P<0.01);UA组TGF-β1表达量为(13.52±3.02) μg/L,显著低于SA组的(26.94±7.25) μg/L和CPS组的(25.93±1.00) μg/L(P<0.01).结论 UA组患者Treg细胞亚群比例降低,Treg细胞亚群与冠状动脉粥样硬化斑块的激活密切相关.

  10. Involvement of distinct PKC gene products in T cell functions

    Directory of Open Access Journals (Sweden)

    Gottfried eBaier

    2012-08-01

    Full Text Available It is well established that members of the Protein kinase C(PKC family seem to have important roles in T cells. Focusing on the physiological and non-redundant PKC functions established in primary mouse T cells via germline gene-targeting approaches, our current knowledge defines two particularly critical PKC gene products, PKCθ and PKCα, as the flavor of PKC in T cells that appear to have a positive role in signaling pathways that are necessary for full antigen receptor-mediated T cell activation ex vivo and T cell-mediated immunity in vivo. Consistently, in spite of the current dogma that PKCθ inhibition might be sufficient to achieve complete immunosuppressive effects, more recent results have indicated that the pharmacological inhibition of PKCθ, and additionally, at least PKCα, appears to be needed to provide a successful approach for the prevention of allograft rejection and treatment of autoimmune diseases.

  11. Development of gonadotropes may involve cyclic transdifferentiation of growth hormone cells.

    Science.gov (United States)

    Childs, G V

    2002-04-01

    The cyclic rise in expression of anterior pituitary gonadotropins coincides with the appearance of cells sharing gonadotropic and somatotropic phenotypes. To learn more about possible factors that regulate the origin of this cell type, we studied the time of appearance of cells that co-expressed growth hormone (GH) and gonadotropins and estrogen receptors during the estrous cycle and compared this timing with known changes in regulatory hormones or their receptors. The first event in this cell population is an increase in expression of estrogen receptor (ER)beta by GH cells from estrus to metestrus suggesting that estrogen may mediate this early change. Expression of GH mRNA rises rapidly from metestrus to mid-cycle. The rise is seen first in GH cells and then in cells with luteinizing hormone (LH) antigens. These data suggest that, early in the cycle, cells bearing GH and growth hormone releasing hormone (GHRH) receptors begin to produce LH and gonadotropin releasing hormone (GnRH) receptors. Early in proestrus, there is an increase in cells with GH and follicle-stimulating hormone (FSH) suggesting that this set of multipotential cells develops later than GH-LH cells. This fits with earlier studies showing the later rise in expression of FSH mRNA. Collectively these data suggest that the anterior pituitary contains a subset of GH cells that have the capacity to respond to multiple releasing hormones and support more than one system.

  12. Irritable bowel syndrome - An inflammatory disease involving mast cells

    OpenAIRE

    Philpott, Hamish; Gibson, Peter; Thien, Frank

    2011-01-01

    Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder - that is the presence of symptoms in the absence of demonstrable pathological abnormalities. In recent times, low grade inflammatory infiltrates in both the small and large bowel of some patients with IBS - often rich in mast cells, along with serological markers of low grade inflammation have focussed attention on IBS as an inflammatory disease. The observation that mast cells often lie in close association to ...

  13. Mechanisms involved in ceramide-induced cell cycle arrest in human hepatocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Jing Wang; Xiao-Wen Lv; Jie-Ping Shi; Xiao-Song Hu

    2007-01-01

    AIM:To investigate the effect of ceramide on the cell cycle in human hepatocarcinoma Bel7402 cells.Possible molecular mechanisms were explored.METHODS:[3-(4,5)-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide(MTT)assay,plasmid transfection,reporter assay,FACS and Western blotting analyses were employed to investigate the effect and the related molecular mechanisms of C2-ceramide on the cell cycle of Bel7402 cells.RESULTS:C2-ceramide was found to inhibit the growth of Bel7402 cells by inducing cell cycle arrest.During the process,the expression of p21 protein increased,while that of cyclinD1,phospho-ERK1/2 and c-myc decreased.Furthermore,the level of CDK7 was downregulated,while the transcriptional activity of PPARγ was upregulated.Addition of GW9662,which is a PPARγ specific antagonist,could reserve the modulation action on CDK7.CONCLUSION:Our results support the hypothesis that cell cycle arrest induced by C2-ceramide may be mediated via accumulation of p21 and reduction of cyclinD1 and CDK7,at least partly,through PPARγ activation.The ERK signaling pathway was involved in this process.

  14. Irritable bowel syndrome - An inflammatory disease involving mast cells.

    Science.gov (United States)

    Philpott, Hamish; Gibson, Peter; Thien, Frank

    2011-04-01

    Irritable bowel syndrome (IBS) is traditionally defined as a functional disorder - that is the presence of symptoms in the absence of demonstrable pathological abnormalities. In recent times, low grade inflammatory infiltrates in both the small and large bowel of some patients with IBS - often rich in mast cells, along with serological markers of low grade inflammation have focussed attention on IBS as an inflammatory disease. The observation that mast cells often lie in close association to enteric neurons, and in-vitro and in-vivo animal studies demonstrating that mast cell mediators may influence enteric motility provides a biologically plausible causal mechanism in IBS. Pilot studies on patients with IBS using the mast cell stabiliser sodium cromoglycate ('proof of concept') have been encouraging. The essential question remains why mast cells infiltrate the bowel of IBS patients. A disturbance of the 'brain-gut axis' is the current favoured hypothesis, whereby childhood stress or psychiatric comorbidity act via neuro-immune mechanisms to modulate low grade inflammation. An alternative hypothesis is that food allergy may be responsible. Serum specific IgE, and skin prick tests are not elevated in IBS patients, suggesting type 1 IgE mediated food allergy is not the cause. However questionnaire based studies indicate IBS patients have higher rates of atopic disease, and increased bronchial reactivity to methacholine has been demonstrated. In this review, we highlight the potential role of mast cells in IBS, and current and future research directions into this intriguing condition.

  15. Growth of Theileria annulata and Theileria parva macroschizont-infected bovine cells in immunodeficient mice: effect of irradiation and tumour load on lymphocyte subsets

    Energy Technology Data Exchange (ETDEWEB)

    Fell, A.H.; Preston, P.M. (Edinburgh Univ. (United Kingdom))

    1992-07-01

    Bovine cells infected with macroschizonts of the protozoan parasites Theileria annulata and Theileria parva formed solid tumours when injected into irradiated Balb/c and irradiated Balb/c nude mice. T. annulata tumours grew more vigorously than T. parva tumours, when initiated with similar doses of infected cells in mice exposed to the same doses of gamma-irradiation. In irradiated Balb/c mice, tumours of both species of parasites began to regress 2-3 weeks after injection of cells but grew without regression in irradiated Balb/c nude mice. Haemorrhage and necrosis of tumours, induced by macrophages and neutrophils, were seen in both mouse strains but were insufficient to cause regression in Balb/c nude mice. Theileria-infected bovine cells failed to establish in C57 beige mice, which lack functional natural killer (NK) cells. Flow cytometry, using monoclonal antibodies to murine leukocyte/lymphocyte antigens, showed that the radiation dose required to allow establishment of T. annulata tumours in Balb/c mice caused a severe depletion of splenic lymphocytes. B cells, helper T and cytotoxic T cells showed differing levels of susceptibility to irradiation. (Author).

  16. Effect of an hydro-alcoholic extract of Uncaria tomentosa (cat's claw) over dendritic cell subsets and HLA-DR/CD86 molecules by lipopolysacarides stimulus

    OpenAIRE

    Lozada-Requena, Ivan; Sección Inmunología. Departamento de Microbiología, facultad de Ciencias y filosofía, universidad Peruana Cayetano Heredia. Lima, Perú. Biólogo.; Núñez, César; Sección Inmunología. Departamento de Microbiología, facultad de Ciencias y filosofía, universidad Peruana Cayetano Heredia. Lima, Perú. Médico Cirujano.; Álvarez, Yubell; Sección Inmunología. Departamento de Microbiología, facultad de Ciencias y filosofía, universidad Peruana Cayetano Heredia. Lima, Perú. Estudiante de Biología.; Aguilar, José Luis; Sección Inmunología. Departamento de Microbiología, facultad de Ciencias y filosofía, universidad Peruana Cayetano Heredia. Lima, Perú. Médico Inmuno-reumatólogo.

    2009-01-01

    Objective. To determine the effect of an hydro-alcoholic extract of cat´s claw Uncaria tomentosa (uG) over lipopolysaccharides – treated dendritic cells (DC) and HLA-DR and CD86 molecules expression of peripheral blood samples obtained from healthy individuals. Materials and methods. Peripheral blood samples were collected from healthy individuals. Peripheral Blood Mononuclear Cells (PBMC) were isolated by centrifugation over density gradient, pre-treated with and without the addition of ...

  17. Aspergillus enzymes involved in degradation of plant cell wall polysaccharides

    NARCIS (Netherlands)

    Vries, de R.P.; Visser, J.

    2001-01-01

    Degradation of plant cell wall polysaccharides is of major importance in the food and feed, beverage, textile, and paper and pulp industries, as well as in several other industrial production processes. Enzymatic degradation of these polymers has received attention for many years and is becoming a m

  18. Granular cell tumor with orbital involvement in a child

    Energy Technology Data Exchange (ETDEWEB)

    Reis, Fabiano [Universidade Estadual de Campinas (FCM/UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Radiologia; Iyeyasu, Josie Naomi; Carvalho, Keila Monteiro de [Universidade Estadual de Campinas (FCM/UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Oftalmo-Otorrinolaringologia; Altemani, Albina Messias [Universidade Estadual de Campinas (FCM/UNICAMP), SP (Brazil). Fac. de Ciencias Medicas. Dept. de Anatomia Patologica

    2011-09-15

    The authors report a rare case of granular cell tumor in the left medial rectus muscle of a seven-year-old boy. Clinical, pathologic and radiologic findings of the present case are described and a brief literature review is undertaken. (author)

  19. Maid (GCIP) is involved in cell cycle control of hepatocytes

    DEFF Research Database (Denmark)

    Sonnenberg-Riethmacher, Eva; Wüstefeld, Torsten; Miehe, Michaela;

    2007-01-01

    . Therefore, we studied the role of Maid during cell cycle progression after partial hepatectomy (PH). Lack of Maid expression after PH was associated with a delay in G1/S-phase progression as evidenced by delayed cyclinA expression and DNA replication in Maid-deficient mice. However, at later time points...

  20. Cells involved in extracellular matrix remodeling after acute myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Larissa Ferraz [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Mataveli, Fábio D’Aguiar [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Mader, Ana Maria Amaral Antônio; Theodoro, Thérèse Rachell [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Justo, Giselle Zenker; Pinhal, Maria Aparecida da Silva [Universidade Federal de São Paulo, São Paulo, SP (Brazil)

    2015-07-01

    Evaluate the effects of VEGF{sub 165} gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF{sub 165} treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF{sub 165}. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF{sub 165}, suggesting greater tissue differentiation. The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF{sub 165} seems to provide a protective effect in the treatment of acute myocardial infarct.

  1. Specific recognition of mycobacterial protein and peptide antigens by gamma-delta T cell subsets following infection with virulent Mycobacterium bovis

    Science.gov (United States)

    Promoting effective immunity to Mycobacterium tuberculosis complex pathogens is a challenge that is of interest to the fields of human and veterinary medicine alike. We report that gamma delta T cells from virulent Mycobacterium bovis-infected cattle respond specifically and directly to complex, pro...

  2. T cell subsets and cytokines in allergic and non-allergic children. I. Analysis of IL-4, IFN-? and IL-13 mRNA expression and protein production

    NARCIS (Netherlands)

    Koning, H.; Neijens, H.J.; Baert, M.R.M.; Oranje, A.P.; Savelkoul, H.F.J.

    1997-01-01

    Interleukin 4 (IL-4) and IL-13 are key cytokines inducing switching to immunoglobulin E (IgE), whereas interferon (IFN-) acts inhibitory on this process. We analysed whether differences existed in IL-4, IFN- and IL-13 mRNA expression and protein production between T cells of children with allergic a

  3. Cytological diagnosis of Langerhans cell histiocytosis with cutaneous involvement

    Directory of Open Access Journals (Sweden)

    Sushama A Chandekar

    2013-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare disease affecting predominantly children. The course of the disease varies, from spontaneous resolution to a progressive multisystem disorder with organ dysfunction and potential life-threatening complications. Diagnosis of LCH is often difficult and may be delayed because of its rarity and especially so if it occurs with unusual presentation. Fine needle aspiration cytology of a 4 year old male child, a case of LCH is presented with a purpose of highlighting the characteristic cytological features. A high index of suspicion, awareness of characteristic cytological features of LCH and its differential diagnoses is necessary. This can obviate the need of biopsy and electron microscopy. Immunohistochemistry if available can be performed on cytology smear and cell block.

  4. THE FEATURE SUBSET SELECTION ALGORITHM

    Institute of Scientific and Technical Information of China (English)

    Liu Yongguo; Li Xueming; Wu Zhongfu

    2003-01-01

    The motivation of data mining is how to extract effective information from huge data in very large database. However, some redundant and irrelevant attributes, which result in low performance and high computing complexity, are included in the very large database in general.So, Feature Subset Selection (FSS) becomes one important issue in the field of data mining. In this letter, an FSS model based on the filter approach is built, which uses the simulated annealing genetic algorithm. Experimental results show that convergence and stability of this algorithm are adequately achieved.

  5. Crypt cells are involved in kin recognition in larval zebrafish

    Science.gov (United States)

    Biechl, Daniela; Tietje, Kristin; Gerlach, Gabriele; Wullimann, Mario F.

    2016-01-01

    Zebrafish larvae imprint on visual and olfactory kin cues at day 5 and 6 postfertilization, respectively, resulting in kin recognition later in life. Exposure to non-kin cues prevents imprinting and kin recognition. Imprinting depends on MHC class II related signals and only larvae sharing MHC class II alleles can imprint on each other. Here, we analyzed which type of olfactory sensory neuron (OSN) detects kin odor. The single teleost olfactory epithelium harbors ciliated OSNs carrying OR and TAAR gene family receptors (mammals: main olfactory epithelium) and microvillous OSNs with V1R and V2R gene family receptors (mammals: vomeronasal organ). Additionally, teleosts exhibit crypt cells which possess microvilli and cilia. We used the activity marker pERK (phosphorylated extracellular signal regulated kinase) after stimulating 9 day old zebrafish larvae with either non-kin conspecific or food odor. While food odor activated both ciliated and microvillous OSNs, only the latter were activated by conspecific odor, crypt cells showed no activation to both stimuli. Then, we tested imprinted and non-imprinted larvae (full siblings) for kin odor detection. We provide the first direct evidence that crypt cells, and likely a subpopulation of microvillous OSNs, but not ciliated OSNs, play a role in detecting a kin odor related signal. PMID:27087508

  6. Efficient activation of human T cells of both CD4 and CD8 subsets by urease-deficient recombinant Mycobacterium bovis BCG that produced a heat shock protein 70-M. tuberculosis-derived major membrane protein II fusion protein.

    Science.gov (United States)

    Mukai, Tetsu; Tsukamoto, Yumiko; Maeda, Yumi; Tamura, Toshiki; Makino, Masahiko

    2014-01-01

    For the purpose of obtaining Mycobacterium bovis bacillus Calmette-Guérin (BCG) capable of activating human naive T cells, urease-deficient BCG expressing a fusion protein composed of Mycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (BCG-DHTM) was produced. BCG-DHTM secreted the HSP70-MMP-II fusion protein and effectively activated human monocyte-derived dendritic cells (DCs) by inducing phenotypic changes and enhanced cytokine production. BCG-DHTM-infected DCs activated naive T cells of both CD4 and naive CD8 subsets, in an antigen (Ag)-dependent manner. The T cell activation induced by BCG-DHTM was inhibited by the pretreatment of DCs with chloroquine. The naive CD8(+) T cell activation was mediated by the transporter associated with antigen presentation (TAP) and the proteosome-dependent cytosolic cross-priming pathway. Memory CD8(+) T cells and perforin-producing effector CD8(+) T cells were efficiently produced from the naive T cell population by BCG-DHTM stimulation. Single primary infection with BCG-DHTM in C57BL/6 mice efficiently produced T cells responsive to in vitro secondary stimulation with HSP70, MMP-II, and M. tuberculosis-derived cytosolic protein and inhibited the multiplication of subsequently aerosol-challenged M. tuberculosis more efficiently than did vector control BCG. These results indicate that the introduction of MMP-II and HSP70 into urease-deficient BCG may be useful for improving BCG for control of tuberculosis.

  7. Human TM9SF4 Is a New Gene Down-Regulated by Hypoxia and Involved in Cell Adhesion of Leukemic Cells.

    Directory of Open Access Journals (Sweden)

    Rosa Paolillo

    Full Text Available The transmembrane 9 superfamily protein member 4, TM9SF4, belongs to the TM9SF family of proteins highly conserved through evolution. TM9SF4 homologs, previously identified in many different species, were mainly involved in cellular adhesion, innate immunity and phagocytosis. In human, the function and biological significance of TM9SF4 are currently under investigation. However, TM9SF4 was found overexpressed in human metastatic melanoma and in a small subset of acute myeloid leukemia (AMLs and myelodysplastic syndromes, consistent with an oncogenic function of this gene.In this study, we first analyzed the expression and regulation of TM9SF4 in normal and leukemic cells and identified TM9SF4 as a gene highly expressed in human quiescent CD34+ hematopoietic progenitor cells (HPCs, regulated during monocytic and granulocytic differentiation of HPCs, both lineages giving rise to mature myeloid cells involved in adhesion, phagocytosis and immunity. Then, we found that TM9SF4 is markedly overexpressed in leukemic cells and in AMLs, particularly in M2, M3 and M4 AMLs (i.e., in AMLs characterized by the presence of a more or less differentiated granulocytic progeny, as compared to normal CD34+ HPCs. Proliferation and differentiation of HPCs occurs in hypoxia, a physiological condition in bone marrow, but also a crucial component of cancer microenvironment. Here, we investigated the impact of hypoxia on TM9SF4 expression in leukemic cells and identified TM9SF4 as a direct target of HIF-1α, downregulated in these cells by hypoxia. Then, we found that the hypoxia-mediated downregulation of TM9SF4 expression is associated with a decrease of cell adhesion of leukemic cells to fibronectin, thus demonstrating that human TM9SF4 is a new molecule involved in leukemic cell adhesion.Altogether, our study reports for the first time the expression of TM9SF4 at the level of normal and leukemic hematopoietic cells and its marked expression at the level of AMLs

  8. Identification of KCa3.1 channel as a novel regulator of Oxidative phosphorylation in a subset of pancreatic carcinoma cell lines

    DEFF Research Database (Denmark)

    Kovalenko, Ilya; Glasauer, Andrea; Schöckel, Laura;

    2016-01-01

    -of-function mutations in p53. Both mutations have severe impacts on the metabolism of tumor cells. Many of these metabolic changes are mediated by transporters or channels that regulate the exchange of metabolites and ions between the intracellular compartment and the tumor microenvironment. In the study presented here......, our goal was to identify novel transporters or channels that regulate oxidative phosphorylation (OxPhos) in PDAC in order to characterize novel potential drug targets for the treatment of these cancers. We set up a Seahorse Analyzer XF based siRNA screen and identified previously described as well...... of a small molecule inhibitor confirmed its role in regulating oxygen consumption, ATP production and cellular proliferation. Furthermore, PDAC cell lines sensitive to KCa3.1 inhibition were shown to express the channel protein in the plasma membrane as well as in the mitochondria. These differences...

  9. Pathologic and Protective Roles for Microglial Subsets and Bone Marrow- and Blood-Derived Myeloid Cells in Central Nervous System Inflammation

    DEFF Research Database (Denmark)

    Wlodarczyk, Agnieszka; Cédile, Oriane; Jensen, Kirstine Nolling;

    2015-01-01

    and also immunoregulation and regenerative processes. Better understanding and characterization of myeloid cell heterogeneity is essential for future development of treatments controlling inflammation and inducing neuroprotection and neuroregeneration in diseased CNS. Here, we describe and compare three......Inflammation is a series of processes designed for eventual clearance of pathogens and repair of damaged tissue. In the context of autoimmune recognition, inflammatory processes are usually considered to be pathological. This is also true for inflammatory responses in the central nervous system...

  10. Ficolin-1 is present in a highly mobilizable subset of human neutrophil granules and associates with the cell surface after stimulation with fMLP

    DEFF Research Database (Denmark)

    Rørvig, Sara; Honoré, Christian Le Fèvre; Larsson, Lars-Inge;

    2009-01-01

    Ficolins are soluble molecules that bind carbohydrate present on the surface of microorganisms and function as recognition molecules in the lectin complement pathway. Three ficolins have been identified in humans: ficolin-1, ficolin-2, and ficolin-3. Ficolin-1 is synthesized in monocytes and type...... associated with the surface membrane of the cells and can be detected by flow cytometry. Our studies show that neutrophils are a major source of ficolin-1, which can be readily exocytosed by stimulation....

  11. Ion channels involved in cell volume regulation: effects on migration, proliferation, and programmed cell death in non adherent EAT cells and adherent ELA cells.

    Science.gov (United States)

    Hoffmann, Else Kay

    2011-01-01

    This mini review outlines studies of cell volume regulation in two closely related mammalian cell lines: nonadherent Ehrlich ascites tumour cells (EATC) and adherent Ehrlich Lettre ascites (ELA) cells. Focus is on the regulatory volume decrease (RVD) that occurs after cell swelling, the volume regulatory ion channels involved, and the mechanisms (cellular signalling pathways) that regulate these channels. Finally, I shall also briefly review current investigations in these two cell lines that focuses on how changes in cell volume can regulate cell functions such as cell migration, proliferation, and programmed cell death.

  12. Hydrogen sulphide, a novel gasotransmitter involved in guard cell signalling.

    Science.gov (United States)

    García-Mata, Carlos; Lamattina, Lorenzo

    2010-12-01

    Hydrogen sulphide (H(2) S) has been proposed as the third gasotransmitter. In animal cells, H(2) S has been implicated in several physiological processes. H(2) S is endogenously synthesized in both animals and plants by enzymes with l-Cys desulphydrase activity in the conversion of l-Cys to H(2) S, pyruvate and ammonia. The participation of H(2) S in both stomatal movement regulation and abscisic acid (ABA)-dependent induction of stomatal closure was studied in epidermal strips of three plant species (Vicia faba, Arabidopsis thaliana and Impatiens walleriana). The effect of H(2) S on stomatal movement was contrasted with leaf relative water content (RWC) measurements of whole plants subjected to water stress. In this work we report that exogenous H(2) S induces stomatal closure and this effect is impaired by the ATP-binding cassette (ABC) transporter inhibitor glibenclamide; scavenging H(2) S or inhibition of the enzyme responsible for endogenous H(2) S synthesis partially blocks ABA-dependent stomatal closure; and H(2) S treatment increases RWC and protects plants against drought stress. Our results indicate that H(2) S induces stomatal closure and participates in ABA-dependent signalling, possibly through the regulation of ABC transporters in guard cells.

  13. γδ T cells are involved in acute HIV infection and associated with AIDS progression.

    Directory of Open Access Journals (Sweden)

    Zhen Li

    Full Text Available BACKGROUND: Early diagnosis is vital to HIV control. γδ T cells play critical roles in viral infections, but their activation in acute HIV infected patients and follow up to 18 months has not been described. METHODS: Changes in γδ T cells, including subsets, function and activation, in treated and untreated acutely HIV-infected patients (n = 79 were compared by cytotoxicity assay and flow cytometry with healthy controls (n = 21 at month 0, 6, 12 and 18. RESULTS: In acutely HIV-infected patients, Vδ1 cell proportion was elevated (P = 0.027 with Vδ2 population reduced (P = 0.002. Effector and central memory γδ T cell factions were decreased (P = 0.006 and P = 0.001, respectively, while proportion of terminal γδ T cells increased (P = 0.002. γδ T cell cytotoxicity was compromised over time. Fraction of IL-17-producing cells increased (P = 0.008, and IFN-γ-producing cells were unaffected (P = 0.115. Elevation of a microbial translocation marker, sCD14, was associated with γδ T cell activation (P = 0.001, which increased in a time-dependent manner, correlating with CD4/CD8 T cell activation set-points and CD4 counts. Antiretroviral therapy did not affect these changes. CONCLUSIONS: γδ T cell subpopulation and functions change significantly in acute HIV infection and over time. Early γδ T cell activation was associated with CD4/CD8 T cell activation set-points, which predict AIDS progression. Therefore, γδ T cell activation represents a potential surrogate marker of AIDS progression.

  14. Analysis of Monocytic and Granulocytic Myeloid-Derived Suppressor Cells Subsets in Patients with Hepatitis C Virus Infection and Their Clinical Significance

    Directory of Open Access Journals (Sweden)

    Gang Ning

    2015-01-01

    Full Text Available Myeloid-derived suppressor cells (MDSCs have been shown to inhibit T-cell responses in many diseases, but, in hepatitis C virus (HCV infected patients, MDSCs are still poorly studied. In this assay, we investigated the phenotype and frequency of two new populations of MDSCs denoted as monocytic and granulocytic MDSCs (M-MDSCs and G-MDSCs in HCV infected patients and analyzed their clinical significance in these patients respectively. We found that the frequency of CD14+HLA-DR-/low cells (M-MDSCs from HCV infected patients (mean ± SE, 3.134% ± 0.340% was significantly increased when compared to healthy controls (mean ± SE, 1.764% ± 0.461% (Z = −2.438, P = 0.015, while there was no statistical difference between the frequency of HLA-DR-/lowCD33+CD11b+CD15+ (G-MDSCs of HCV infected patients and healthy donors (0.201% ± 0.038% versus 0.096% ± 0.026%, P > 0.05, which suggested that HCV infection could cause the proliferation of M-MDSCs instead of G-MDSCs. Besides, we found that the frequency of M-MDSCs in HCV infected patients had certain relevance with age (r = 0.358, P = 0.003; patients older than 40 years old group (mean ± SE, 3.673% ± 0.456% had a significantly higher frequency of M-MDSCs than that of age less than 40 years old group (mean ± SE, 2.363% ± 0.482% (Z = −2.685, P = 0.007. The frequency of M-MDSCs, however, had no correlation with HCV RNA loads, aspartate aminotransferase (AST, alanine aminotransferase (ALT, and the level of liver inflammation degree.

  15. Predictive validity and immune cell involvement in the pathogenesis of piroxicam-accelerated colitis in interleukin-10 knockout mice.

    Science.gov (United States)

    Holgersen, Kristine; Kvist, Peter Helding; Hansen, Axel Kornerup; Holm, Thomas Lindebo

    2014-07-01

    Piroxicam administration is a method for induction of enterocolitis in interleukin-10 knockout (IL-10 k.o.) mice. The piroxicam-accelerated colitis (PAC) IL-10 k.o. model combines a dysregulated immune response against the gut microbiota with a decreased mucosal integrity. The predictive validity and pathogenic mechanisms of the model have not been thoroughly investigated. In this study, IL-10 k.o. mice received piroxicam in the chow, and model qualification was performed by examining the efficacy of prophylactic anti-IL-12/23p40 monoclonal antibody (mAb), anti-TNFα mAb, cyclosporine A (CsA) and oral prednisolone treatment. To evaluate cell involvement in the disease pathogenesis, specific cell subsets were depleted by treatment with anti-CD4 mAb, anti-CD8 mAb or clodronate-encapsulated liposomes. T cell receptor co-stimulation was blocked by CTLA4-Ig. Cytokine profiling ELISAs and calprotectin immunohistochemistry were performed on colon tissue. Treatments with anti-IL-12/23p40 mAb and CsA prevented disease in PAC IL-10 k.o. mice and reduced IFNγ, IL-17A, MPO and calprotectin levels in colon. Anti-TNFα mAb treatment caused amelioration of selected clinical parameters. No effect of prednisolone was detected. Depletion of CD8(+) cells tended to increase mortality, whereas treatment with anti-CD4 mAb or CTLA4-Ig had no significant effect on disease development. Clodronate liposome treatment induced a loss of body weight; nevertheless macrophage depletion was associated with a significant reduction in colonic pathology. In conclusion, reference drugs with known efficacy in severe inflammatory bowel disease were efficacious in the PAC IL-10 k.o. model. Our data indicate that in this model macrophages are a main driver of colitis, whereas CD4(+) cells are not.

  16. A community study of T lymphocyte subsets and malaria parasitaemia

    DEFF Research Database (Denmark)

    Lisse, I M; Aaby, P; Whittle, H

    1994-01-01

    In a community survey of 312 children aged 3-6 years in urban Guinea-Bissau, we examined Plasmodium falciparum parasitaemia and T cell subsets. 183 children (59%) had parasites in their blood, 13 had fever > or = 37.5 degrees C, and 9 (3%) had fever and a parasite density > 5000/microL (clinical...... parasites (P = 0.024), whereas there was no association with CD8 cell percentage or the CD4/CD8 ratio. Asymptomatic parasitaemia may be an important confounder in general community studies of T cell subsets in the tropics....

  17. AID expression in peripheral blood of children living in a malaria endemic region is associated with changes in B cell subsets and Epstein-Barr virus

    Science.gov (United States)

    Wilmore, Joel R; Asito, Amolo S; Wei, Chungwen; Piriou, Erwan; Sumba, P. Odada; Sanz, Iñaki

    2015-01-01

    The development of endemic Burkitt's lymphoma (eBL) is closely associated with EBV infection and holoendemic malaria infections. The role of EBV in the development of malignancy has been studied in depth, but there is still little known about the mechanisms by which malaria affects Burkitt's lymphomagenesis. Activation induced cytidine deaminase (AID) expression is necessary for the introduction of c-myc translocations that are characteristic of BL, but a link between AID and EBV or malaria is unclear. To determine if frequency of malaria exposure leads to increased AID expression in peripheral blood mononuclear cells (PBMC) we examined two cohorts of children in western Kenya with endemic and sporadic malaria transmission dynamics. High frequency of malaria exposure led to increased expression of AID, which coincided with decreases in the IgM+ memory B cells. In the children from the malaria endemic region, the presence of a detectible EBV viral load was associated with higher AID expression compared to children with undetectable EBV, but this effect was not seen in children with sporadic exposure to malaria. This study demonstrates that intensity of malaria transmission correlates with AID expression levels in the presence of EBV suggesting that malaria and EBV infection have a synergistic effect on the development of c-myc translocations and BL. PMID:25099163

  18. AID expression in peripheral blood of children living in a malaria holoendemic region is associated with changes in B cell subsets and Epstein-Barr virus.

    Science.gov (United States)

    Wilmore, Joel R; Asito, Amolo S; Wei, Chungwen; Piriou, Erwan; Sumba, P Odada; Sanz, Iñaki; Rochford, Rosemary

    2015-03-15

    The development of endemic Burkitt's lymphoma (eBL) is closely associated with Epstein-Barr virus (EBV) infection and holoendemic malaria infections. The role of EBV in the development of malignancy has been studied in depth, but there is still little known about the mechanisms by which malaria affects Burkitt's lymphomagenesis. Activation induced cytidine deaminase (AID) expression is necessary for the introduction of c-myc translocations that are characteristic of BL, but a link between AID and EBV or malaria is unclear. To determine whether frequency of malaria exposure leads to increased AID expression in peripheral blood mononuclear cells (PBMC) we examined two cohorts of children in western Kenya with endemic and sporadic malaria transmission dynamics. High frequency of malaria exposure led to increased expression of AID, which coincided with decreases in the IgM(+) memory B cells. In the children from the malaria endemic region, the presence of a detectible EBV viral load was associated with higher AID expression compared to children with undetectable EBV, but this effect was not seen in children with sporadic exposure to malaria. This study demonstrates that intensity of malaria transmission correlates with AID expression levels in the presence of EBV suggesting that malaria and EBV infection have a synergistic effect on the development of c-myc translocations and BL.

  19. Activating E17K mutation in the gene encoding the protein kinase AKT1 in a subset of squamous cell carcinoma of the lung.

    Science.gov (United States)

    Malanga, Donatella; Scrima, Marianna; De Marco, Carmela; Fabiani, Fernanda; De Rosa, Nicla; De Gisi, Silvia; Malara, Natalia; Savino, Rocco; Rocco, Gaetano; Chiappetta, Gennaro; Franco, Renato; Tirino, Virginia; Pirozzi, Giuseppe; Viglietto, Giuseppe

    2008-03-01

    Somatic mutation (E17K) that constitutively activates the protein kinase AKT1 has been found in human cancer patients. We determined the role of the E17K mutation of AKT1 in lung cancer, through sequencing of AKT1 exon 4 in 105 resected, clinically annotated non-small cell lung cancer specimens. We detected a missense mutations G-->A transition at nucleotide 49 (that results in the E17K substitution) in two squamous cell carcinoma (2/36) but not in adenocarcinoma (0/53). The activity of the endogenous kinase carrying the E17K mutation immunoprecipitated by tumour tissue was significantly higher compared with the wild-type kinase immunoprecipitated by the adjacent normal tissue as determined both by in vitro kinase assay using a consensus peptide as substrate and by in vivo analysis of the phosphorylation status of AKT1 itself (pT308, pS473) or of known downstream substrates such as GSK3 (pS9/S22) and p27 (T198). Immunostaining or immunoblot analysis on membrane-enriched extracts indicated that the enhanced membrane localization exhibited by the endogenous E17K-AKT1 may account for the observed increased activity of mutant E17K kinase in comparison with the wild-type AKT1 from adjacent normal tissue. In conclusion, this is the first report of AKT1 mutation in lung cancer. Our data provide evidence that, although AKT1 mutations are apparently rare in lung cancer (1.9%), the oncogenic properties of E17K-AKT1 may contribute to the development of a fraction of lung carcinoma with squamous histotype (5.5%).

  20. Increased p16CDKN2A protein within feline cutaneous viral plaques, bowenoid in situ carcinomas, and a subset of invasive squamous cell carcinomas.

    Science.gov (United States)

    Munday, J S; French, A F; Peters-Kennedy, J; Orbell, G M B; Gwynne, K

    2011-03-01

    Cutaneous viral plaques and bowenoid in situ carcinomas (BISCs) in cats are thought to be caused by papillomavirus (PV) infection. There is evidence that PVs may also cause some feline invasive squamous cell carcinomas (ISCCs). Human oncogenic PVs degrade retinoblastoma (RB) protein, impairing cell cycle control. Loss of RB function also increases p16(CDKN2A) protein (p16), and increased p16 immunoreactivity within a human oral ISCC indicates that the neoplasm was caused by PV infection. In the present study, p16 immunoreactivity was evaluated in 14 feline viral plaques, 14 BISCs, 7 non-solar-induced ISCCs, 11 solar-induced ISCCs, and 14 trichoblastomas. Increased p16 was present within all viral plaques, BISCs, and non-solar-induced ISCCs. In contrast, little p16 immunoreactivity was visible in the solar-induced ISCCs or trichoblastomas. PV DNA was consistently amplified from viral plaques, BISCs, and non-solar-induced ISCCs. However, just 5 solar-induced ISCCs and 1 trichoblastoma contained PV DNA. Given that both increased p16 immunoreactivity and PV DNA were present within viral plaques, BISCs, and non-solar-induced ISCCs, all 3 may be caused by PV infection. This suggests that feline non-solar-induced ISCCs may develop as a result of neoplastic progression from viral plaques and BISCs. Whether PVs promote this progression is unknown; however, evidence from this study suggests the PV that is associated with viral plaques and BISCs is able to disrupt the p16-RB pathway and therefore could have oncogenic potential. Immunohistochemical detection of p16 appears to be a useful technique to investigate the role of PVs in feline skin disease.

  1. Analysis of regulatory T-cells and of their naïve and memory-like subsets in long-term treated aviremic HIV+ patients and untreated viremic patients

    Directory of Open Access Journals (Sweden)

    L Imberti

    2012-11-01

    Full Text Available Purpose of the study: Although HIV infection impacts the proportion and phenotype of regulatory T-cells (Tregs, discrepant results have been reported depending on the surface markers employed to characterize them and on the patient populations. In addition, the effects of a long-term combined antiretroviral therapy (cART on Treg cells have not been thoroughly documented. Our study investigated the frequency and number of Tregs and their phenotype in two different groups of HIV-infected patients: one aviremic undergoing long-term cART and one viremic naïve to cART showing a similar CD4+ cell count. Methods: Thirty-six HIV+ patients with sustained suppression of plasma viremia (<37 copies/mL on effective cART for more than 6 years and 22 HIV+patients naïve to cART and without clinical signs of opportunistic infections or tumors at the time of study (untreated group were included in the study. Healthy donors (HD were used as control. Flow cytometry on fresh whole blood was used to quantify total Tregs (defined as CD25+CD127low/-CD4+ cells and the following Treg subsets: naïve (CD45RA+CCR7+ Tregs, central-memory like Tregs (CD45RA-CCR7+, TregCM, effector-memory like Tregs (CD45RA-CCR7−, TregEM Statistical comparisons of the percentages and number of Tregs and Treg subpopulations were performed by ANOVA or Kruskal-Wallis test. Analysis of covariance was employed in order to adjust for the effect of the age. The Spearman's test was used to assess correlations. Summary of results: In viremic untreated and aviremic long-term cART-treated patients the percentage and number of the total Treg cells were not different from those of HD. However, the analysis of Treg phenotype showed a marked redistribution of the Treg subpopulations: in the untreated viremic patients, both the percentage and number of the TregCM subset decreased compared to HD and cART-treated patients, whereas only the percentage of naïve Tregs increased. In particular, the percentage

  2. Pathophysiological significance of the two-pore domain K+ channel K2P5.1 in splenic CD4+CD25− T cell subset from a chemically-induced murine inflammatory bowel disease model

    Science.gov (United States)

    Nakakura, Sawa; Matsui, Miki; Sato, Aya; Ishii, Mizuki; Endo, Kyoko; Muragishi, Sayaka; Murase, Miki; Kito, Hiroaki; Niguma, Hiroki; Kurokawa, Natsumi; Fujii, Masanori; Araki, Masatake; Araki, Kimi; Ohya, Susumu

    2015-01-01

    The alkaline pH-activated, two-pore domain K+ channel K2P5.1 (also known as TASK2/KCNK5) plays an important role in maintaining the resting membrane potential, and contributes to the control of Ca2+ signaling in several types of cells. Recent studies highlighted the potential role of the K2P5.1 K+ channel in the pathogenesis of autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. The aim of the present study was to elucidate the pathological significance of the K2P5.1 K+ channel in inflammatory bowel disease (IBD). The degrees of colitis, colonic epithelial damage, and colonic inflammation were quantified in the dextran sulfate sodium-induced mouse IBD model by macroscopic and histological scoring systems. The expression and functional activity of K2P5.1 in splenic CD4+ T cells were measured using real-time PCR, Western blot, and fluorescence imaging assays. A significant increase was observed in the expression of K2P5.1 in the splenic CD4+ T cells of the IBD model. Concomitant with this increase, the hyperpolarization response induced by extracellular alkaline pH was significantly larger in the IBD model with the corresponding intracellular Ca2+ rises. The expression of K2P5.1 was higher in CD4+CD25− T cells than in CD4+CD25+ regulatory T cells. The knockout of K2P5.1 in mice significantly suppressed the disease responses implicated in the IBD model. Alternations in intracellular Ca2+ signaling following the dysregulated expression of K2P5.1 were associated with the disease pathogenesis of IBD. The results of the present study suggest that the K2P5.1 K+ channel in CD4+CD25− T cell subset is a potential therapeutic target and biomarker for IBD. PMID:26578971

  3. The involvement of glucose-6-phosphatase in mucilage secretion by root cap cells of Zea mays

    Science.gov (United States)

    Moore, R.; McClelen, C. E.

    1985-01-01

    In order to determine the involvement of glucose-6-phosphatase in mucilage secretion by root cap cells, we have cytochemically localized the enzyme in columella and peripheral cells of root caps of Zea mays. Glucose-6-phosphatase is associated with the plasmalemma and cell wall of columella cells. As columella cells differentiate into peripheral cells and begin to produce and secrete mucilage, glucose-6-phosphatase staining intensifies and becomes associated with the mucilage and, to a lesser extent, the cell wall. Cells being sloughed from the cap are characterized by glucose-6-phosphatase staining being associated with the vacuole and plasmalemma. These changes in enzyme localization during cellular differentiation in root caps suggest that glucose-6-phosphatase is involved in the production and/or secretion of mucilage by peripheral cells of Z. mays.

  4. The Hagfish Gland Thread Cell: A Fiber-Producing Cell Involved in Predator Defense

    Directory of Open Access Journals (Sweden)

    Douglas S. Fudge

    2016-05-01

    Full Text Available Fibers are ubiquitous in biology, and include tensile materials produced by specialized glands (such as silks, extracellular fibrils that reinforce exoskeletons and connective tissues (such as chitin and collagen, as well as intracellular filaments that make up the metazoan cytoskeleton (such as F-actin, microtubules, and intermediate filaments. Hagfish gland thread cells are unique in that they produce a high aspect ratio fiber from cytoskeletal building blocks within the confines of their cytoplasm. These threads are elaborately coiled into structures that readily unravel when they are ejected into seawater from the slime glands. In this review we summarize what is currently known about the structure and function of gland thread cells and we speculate about the mechanism that these cells use to produce a mechanically robust fiber that is almost one hundred thousand times longer than it is wide. We propose that a key feature of this mechanism involves the unidirectional rotation of the cell’s nucleus, which would serve to twist disorganized filaments into a coherent thread and impart a torsional stress on the thread that would both facilitate coiling and drive energetic unravelling in seawater.

  5. Involvement of CD244 in regulating CD4+ T cell immunity in patients with active tuberculosis.

    Directory of Open Access Journals (Sweden)

    Bingfen Yang

    Full Text Available CD244 (2B4 is a member of the signaling lymphocyte activation molecule (SLAM family of immune cell receptors and it plays an important role in modulating NK cell and CD8(+ T cell immunity. In this study, we investigated the expression and function of CD244/2B4 on CD4(+ T cells from active TB patients and latent infection individuals. Active TB patients had significantly elevated CD244/2B4 expression on M. tuberculosis antigen-specific CD4(+ T cells compared with latent infection individuals. The frequencies of CD244/2B4-expressing antigen-specific CD4(+ T cells were significantly higher in retreatment active TB patients than in new active TB patients. Compared with CD244/2B4-dull and -middle CD4(+ T cells, CD244/2B4-bright CD4(+ T cell subset had significantly reduced expression of IFN-γ, suggesting that CD244/2B4 expression may modulate IFN-γ production in M. tuberculosis antigen-responsive CD4(+ T cells. Activation of CD244/2B4 signaling by cross-linking led to significantly decreased production of IFN-γ. Blockage of CD244/2B4 signaling pathway of T cells from patients with active TB resulted in significantly increased production of IFN-γ, compared with isotype antibody control. In conclusion, CD244/2B4 signaling pathway has an inhibitory role on M. tuberculosis antigen-specific CD4(+ T cell function.

  6. Increased CD4 and CD8-positive T cell infiltrate signifies good prognosis in a subset of triple-negative breast cancer.

    Science.gov (United States)

    Matsumoto, Hirofumi; Thike, Aye Aye; Li, Huihua; Yeong, Joe; Koo, Si-Lin; Dent, Rebecca Alexandra; Tan, Puay Hoon; Iqbal, Jabed

    2016-04-01

    Tumour-infiltrating lymphocytes (TILs) signify immune response to tumour in a variety of cancers including breast cancer. However, earlier studies examining the clinical significance of TILs in breast cancers have generated mixed results. There are only a few that address the relationship between TILs and clinical outcomes in triple-negative breast cancers (TNBC). The aim of this study is to evaluate the clinical significance of TILs that express CD4 + and CD8 + , in TNBC. Immunohistochemical staining of CD4 and CD8 was performed on tissue microarrays of 164 cases of TNBC. TILs were counted separately as intratumoral when within the cancer cell nests (iTILs) and as stromal when within cancer stroma (sTILs). High CD8 + iTILs and sTILs, and CD4 + iTILs correlated with histologic grade. On Kaplan-Meier analysis, a significantly better survival rate was observed in high CD8 + iTIL (disease-free survival, DFS: P = 0.004, overall survival, OS: P = 0.02) and both high CD4 + iTILs (DFS: P = 0.025, OS: P = 0.023) and sTILs (DFS: P = 0.01, OS: P = 0.002). In multivariate analysis, CD8 + iTILs (DFS: P = 0.0095), CD4 + sTILs (DFS: P = 0.0084; OS: P = 0.0118), and CD4 (high) CD8 (high) CD8 iTILs (DFS: P = 0.0121; OS: P = 0.0329) and sTILs (DFS: P = 0.0295) showed significantly better survival outcomes. These results suggest that high levels of both CD8 + iTILs and CD4 + sTILs as well as CD4 (high) CD8 (high) iTILs and sTILs are independent prognostic factors in TNBC.

  7. Mining Representative Subset Based on Fuzzy Clustering

    Institute of Scientific and Technical Information of China (English)

    ZHOU Hongfang; FENG Boqin; L(U) Lintao

    2007-01-01

    Two new concepts-fuzzy mutuality and average fuzzy entropy are presented. Then based on these concepts, a new algorithm-RSMA (representative subset mining algorithm) is proposed, which can abstract representative subset from massive data.To accelerate the speed of producing representative subset, an improved algorithm-ARSMA(accelerated representative subset mining algorithm) is advanced, which adopt combining putting forward with backward strategies. In this way, the performance of the algorithm is improved. Finally we make experiments on real datasets and evaluate the representative subset. The experiment shows that ARSMA algorithm is more excellent than RandomPick algorithm either on effectiveness or efficiency.

  8. Quantum dot-induced cell death involves Fas upregulation and lipid peroxidation in human neuroblastoma cells

    Directory of Open Access Journals (Sweden)

    Lovrić Jasmina

    2007-02-01

    Full Text Available Abstract Background Neuroblastoma, a frequently occurring solid tumour in children, remains a therapeutic challenge as existing imaging tools are inadequate for proper and accurate diagnosis, resulting in treatment failures. Nanoparticles have recently been introduced to the field of cancer research and promise remarkable improvements in diagnostics, targeting and drug delivery. Among these nanoparticles, quantum dots (QDs are highly appealing due to their manipulatable surfaces, yielding multifunctional QDs applicable in different biological models. The biocompatibility of these QDs, however, remains questionable. Results We show here that QD surface modifications with N-acetylcysteine (NAC alter QD physical and biological properties. In human neuroblastoma (SH-SY5Y cells, NAC modified QDs were internalized to a lesser extent and were less cytotoxic than unmodified QDs. Cytotoxicity was correlated with Fas upregulation on the surface of treated cells. Alongside the increased expression of Fas, QD treated cells had increased membrane lipid peroxidation, as measured by the fluorescent BODIPY-C11 dye. Moreover, peroxidized lipids were detected at the mitochondrial level, contributing to the impairment of mitochondrial functions as shown by the MTT reduction assay and imaged with confocal microscopy using the fluorescent JC-1 dye. Conclusion QD core and surface compositions, as well as QD stability, all influence nanoparticle internalization and the consequent cytotoxicity. Cadmium telluride QD-induced toxicity involves the upregulation of the Fas receptor and lipid peroxidation, leading to impaired neuroblastoma cell functions. Further improvements of nanoparticles and our understanding of the underlying mechanisms of QD-toxicity are critical for the development of new nanotherapeutics or diagnostics in nano-oncology.

  9. Salamander limb regeneration involves the activation of a multipotent skeletal muscle satellite cell population.

    Science.gov (United States)

    Morrison, Jamie I; Lööf, Sara; He, Pingping; Simon, András

    2006-01-30

    In contrast to mammals, salamanders can regenerate complex structures after injury, including entire limbs. A central question is whether the generation of progenitor cells during limb regeneration and mammalian tissue repair occur via separate or overlapping mechanisms. Limb regeneration depends on the formation of a blastema, from which the new appendage develops. Dedifferentiation of stump tissues, such as skeletal muscle, precedes blastema formation, but it was not known whether dedifferentiation involves stem cell activation. We describe a multipotent Pax7+ satellite cell population located within the skeletal muscle of the salamander limb. We demonstrate that skeletal muscle dedifferentiation involves satellite cell activation and that these cells can contribute to new limb tissues. Activation of salamander satellite cells occurs in an analogous manner to how the mammalian myofiber mobilizes stem cells during skeletal muscle tissue repair. Thus, limb regeneration and mammalian tissue repair share common cellular and molecular programs. Our findings also identify satellite cells as potential targets in promoting mammalian blastema formation.

  10. Involvement of epigenetic modifiers in the pathogenesis of testicular dysgenesis and germ cell cancer

    DEFF Research Database (Denmark)

    Lawaetz, Andreas C.; Almstrup, Kristian

    2015-01-01

    Testicular germ cell cancer manifests mainly in young adults as a seminoma or non-seminoma. The solid tumors are preceded by the presence of a non-invasive precursor cell, the carcinoma in situ cell (CIS), which shows great similarity to fetal germ cells. It is therefore hypothesized that the CIS...... of epigenetic modifiers with a focus on jumonji C enzymes in the development of testicular dysgenesis and germ cell cancer in men....... cell is a fetal germ cell that has been arrested during development due to testicular dysgenesis. CIS cells retain a fetal and open chromatin structure, and recently several epigenetic modifiers have been suggested to be involved in testicular dysgenesis in mice. We here review the possible involvement...

  11. P12 - PTHC1: A Continuing Cell Line Expressing PTH and Genes Involved in Calcium Homeostasis

    OpenAIRE

    Fabbri, S.; Mazzotta, C.; Ciuffi, S.; Mavilia, C; Galli, G; Zonefrati, R.; Strigoli, D.; Cavalli, L.; Cavalli, T.; Brandi, M L

    2010-01-01

    The main organs regulating serum levels of ionised calcium (Ca2+) are the parathyroids, which are composed of two different cell types: chief cells and oxyphil cells. Chief cells, through the calcium sensing receptor (CaSR), are affected by changes in calcium concentration, modifying PTH secretion in proportion to calcium levels. Current understanding of calcium regulation mechanisms connected to PTH and of the signalling pathways involved derive from in vitro studies carried out on primary c...

  12. Pulmonary Involvement of Peripheral T-cell Lymphoma, Unspecified: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Jin; Shim, Hyo Sub; Ham, Seok Jin; Kim, Tae Hoon; Kim, Sang Jin [Gangnam Severance Hospital, Seoul (Korea, Republic of)

    2010-01-15

    Peripheral T-cell lymphoma is a rare type of lymphoma that's derived from postthymic lymphoid T cells. Pulmonary involvement of peripheral T-cell lymphoma of the unspecified type is very rare and the imaging findings of this illness have rarely been reported. We present here a case of peripheral T-cell lymphoma of the unspecified type with a cavitary lesion in the lung parenchyma, and we pathologically confirmed this illness by performing video-assisted thoracoscopic surgery.

  13. Decreased expression of the plasminogen activator inhibitor type 1 is involved in degradation of extracellular matrix surrounding cervical cancer stem cells.

    Science.gov (United States)

    Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Takahashi, Juri; Kojima, Satoko; Yamashita, Aki; Tomio, Kensuke; Nagamatsu, Takeshi; Wada-Hiraike, Osamu; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-02-01

    The plasminogen activator (PA) system consists of plasminogen activator inhibitor type 1 (PAI-1), urokinase-type plasminogen activator and its receptor (uPA and uPAR). PAI-1 inhibits the activation of uPA (which converts plasminogen to plasmin), and is involved in cancer invasion and metastasis, by remodeling the extracellular matrix (ECM) through regulating plasmin. Cancer stem cells (CSCs) are a small subset of cells within tumors, and are thought to be involved in tumor recurrence and metastasis. Considering these facts, we investigated the relationship between PAI-1 and cervical CSCs. We used ALDH1 as a marker of cervical CSCs. First, we demonstrated that culturing ALDH1-high cells and ALDH-low cells on collagen IV-coted plates increased their expression of active PAI-1 (ELISA), and these increases were suggested to be at mRNA expression levels (RT-qPCR). Secondly, we demonstrated PAI-1 was indeed involved in the ECM maintenance. With gelatin zymography assays, we found that ALDH1-high cells and ALDH-low cells expressed pro-matrix metalloproteinase-2 (pro-MMP-2) irrespective of their coatings. With gelatinase/collagenase assay kit, we confirmed that collagenase activity was increased when ALDH1-low cells were exposed to TM5275, a small molecule inhibitor of PAI-1. Putting the data together, we hypothesized that cancer cells adhered to basal membrane secrete abundant PAI-1, on the other hand, cancer cells (especially CSCs rather than non-CSCs) distant from basal membrane secrete less PAI-1, which makes the ECM surrounding CSCs more susceptible to degradation. Our study could be an explanation of conflicting reports, where some researchers found negative impacts of PAI-1 expression on clinical outcomes and others not, by considering the concept of CSCs.

  14. B-cell exposure to self-antigen induces IL-10 producing B cells as well as IL-6- and TNF-α-producing B-cell subsets in healthy humans

    DEFF Research Database (Denmark)

    Langkjær, Anina; Kristensen, Birte; Hansen, Bjarke E

    2012-01-01

    of IL-10 and TGF-β, in addition to TNF-α and IL-6. Pulsing with foreign antigen, tetanus toxoid (TT), induced a Th1-response with minimal IL-10 production. After thyroglobulin-pulsing, 1.10±0.50% of B cells and 1.00±0.20% of CD4(+) T cells produced IL-10, compared to 0.29±0.19% of B cells (P=0.01) and 0...... cells mediate self-antigen-specific IL-10, TNF-α and IL-6 production in co-cultures with T cells and contribute actively to these cytokine secretions.......Human B cells are able to secrete IL-10 after stimulation with mitogens, but their ability to produce IL-10 and regulate T-cell responses after stimulation with self-antigens is unclear. We co-cultured thyroglobulin-pulsed B cells from healthy donors with autologous T cells and observed production...

  15. Involvement of proliferating cell nuclear antigen (Cyclin) in DNA replication in living cells

    Energy Technology Data Exchange (ETDEWEB)

    Zuber, M.; Tan, E.M.; Ryoji, M.

    1989-01-01

    Proliferating cell nuclear antigen (PCNA) (also called cyclin) is known to stimulate the activity of DNA polymerase /delta/ but not the other DNA polymerases in vitro. The authors injected a human autoimmune antibody against PCNA into unfertilized eggs of Xenopus laevis and examined the effects of this antibody on the replication of injected plasmid DNA as well as egg chromosomes. The anti-PCNA antibody inhibited plasmid replication by up to 67%, demonstrating that PCNA is involved in plasmid replication in living cells. This result further implies that DNA polymerase /delta/ is necessary for plasmid replication in vivo, Anti-PCNA antibody alone did not block plasmid replication completely, but the residual replication was abolished by coinjection of a monoclonal antibody against DNA polymerase /alpha/. Anti-DNA polymerase /alpha/ alone inhibited plasmid replication by 63%. Thus, DNA ploymerase /alpha/ is also required for plasmid replication in this system. In similar studies on the replication of egg chromosomes, the inhibition by anti-PCNA antibody was only 30%, while anti-DNA polymerase /alpha/ antibody blocked 73% of replication. They concluded that the replication machineries of chromosomes and plasmid differ in their relative content of DNA polymerase /delta/. In addition, they obtained evidence through the use of phenylbutyl deoxyguanosine, an inhibitor of DNA polymearse /alpha/, that the structure of DNA polymerase /alpha/ holoenzyme for chromosome replication is significantly different from that for plasmid replication.

  16. Acute myeloid dendritic cell leukaemia with specific cutaneous involvement: a diagnostic challenge.

    Science.gov (United States)

    Ferran, M; Gallardo, F; Ferrer, A M; Salar, A; Pérez-Vila, E; Juanpere, N; Salgado, R; Espinet, B; Orfao, A; Florensa, L; Pujol, R M

    2008-05-01

    Myeloid or type 1 dendritic cell leukaemia is an exceedingly rare haematopoietic neoplasm characterized by a specific immunophenotypic profile close to plasmacytoid dendritic cell and acute myelogenous leukaemia. A 77-year-old man presenting specific cutaneous infiltration by myeloid dendritic cell leukaemia is reported. The clinical features as well as the cutaneous histopathological and immunohistochemical features led to the initial diagnosis of CD4+/CD56+ haematodermic neoplasm. However, extensive immunophenotypic studies performed from peripheral blood blasts disclosed that leukaemic cells expressed myeloid dendritic cell markers, confirming the diagnosis. The diagnostic difficulties of specific cutaneous involvement by myeloid dendritic cell leukaemia on the basis of routine histopathological and immunohistochemical features are highlighted.

  17. Critical role of PI3K signaling for NF-kappaB-dependent survival in a subset of activated B-cell-like diffuse large B-cell lymphoma cells.

    Science.gov (United States)

    Kloo, Bernhard; Nagel, Daniel; Pfeifer, Matthias; Grau, Michael; Düwel, Michael; Vincendeau, Michelle; Dörken, Bernd; Lenz, Peter; Lenz, Georg; Krappmann, Daniel

    2011-01-04

    The activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL) represents a very aggressive human lymphoma entity. Constitutive NF-κB activation caused by chronic active B-cell receptor (BCR) signaling is common feature of many ABC DLBCL cells; however, the pathways linking BCR signaling to the NF-κB prosurvival network are largely unknown. Here we report that constitutive activity of PI3K and the downstream kinase PDK1 are essential for the viability of two ABC DLBCL cell lines that carry mutations in the BCR proximal signaling adaptor CD79B. In these cells, PI3K inhibition reduces NF-κB activity and decreases the expression of NF-κB target genes. Furthermore, PI3K and PDK1 are required for maintaining MALT1 protease activity, which promotes survival of the affected ABC DLBCL cells. These results demonstrate a critical function of PI3K-PDK1 signaling upstream of MALT1 protease and NF-κB in distinct ABC DLBCL cells and provide a rationale for the pharmacologic use of PI3K inhibitors in DLBCL therapy.

  18. Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity.

    Science.gov (United States)

    Rouvier, E; Luciani, M F; Golstein, P

    1993-01-01

    Mechanisms of T cell-mediated cytotoxicity remain poorly defined at the molecular level. To investigate some of these mechanisms, we used as target cells, on the one hand, thymocytes from lpr and gld mouse mutants, and on the other hand, L1210 cells transfected or not with the apoptosis-inducing Fas molecule. These independent mutant or transfectant-based approaches both led to the conclusion that Fas was involved in the Ca(2+)-independent component of cytotoxicity mediated by at least two sources of T cells, namely nonantigen-specific in vitro activated hybridoma cells, and antigen-specific in vivo raised peritoneal exudate lymphocytes. Thus, in these cases, T cell-mediated cytotoxicity involved transduction via Fas of the target cell death signal.

  19. Human natural regulatory T cells subsets

    OpenAIRE

    Lei, Hong

    2014-01-01

    Regulatorische T-Zellen (Treg) eröffnen neue immuntherapeutische Wege zur Kontrolle unerwünschter Immunreaktionen, jedoch wirft die Heterogenität dieser Zellen die Frage auf, welche Treg-Population für die klinische Anwendung. Darauf basierend werden in dieser Arbeit drei Fragestellungen bearbeitet: i) Bestimmung der Häufigkeit von Tregs und deren Subpopulationen in verschiedenen Altersgruppen bei Empfängern einer Organtransplantation (Tx) und einer gesunden Kontrollgruppe; ii) Vergleich der ...

  20. Characterizing primary human microglia: A comparative study with myeloid subsets and culture models.

    Science.gov (United States)

    Melief, J; Sneeboer, M A M; Litjens, M; Ormel, P R; Palmen, S J M C; Huitinga, I; Kahn, R S; Hol, E M; de Witte, L D

    2016-11-01

    The biology of microglia has become subject to intense study, as they are widely recognized as crucial determinants of normal and pathologic brain functioning. While they are well studied in animal models, it is still strongly debated what specifies most accurately the phenotype and functioning of microglia in the human brain. In this study, we therefore isolated microglia from postmortem human brain tissue of corpus callosum (CC) and frontal cortex (CTX). The cells were phenotyped for a panel of typical microglia markers and genes involved in myeloid cell biology. Furthermore, their response to pro- and anti-inflammatory stimuli was assessed. The microglia were compared to key human myeloid cell subsets, including monocytes, monocyte-derived macrophages and monocyte-derived dendritic cells, and several commonly used microglial cell models. Protein and mRNA expression profiles partly differed between microglia isolated from CC and frontal cortex and were clearly distinct from other myeloid subsets. Microglia responded to both pro- (LPS or poly I:C) and anti-inflammatory (IL-4 or dexamethasone) stimuli. Interestingly, pro-inflammatory responses differed between microglia and monocyte-derived macrophages, as the former responded more strongly to poly I:C and the latter more strongly to LPS. Furthermore, we defined a large phenotypic discrepancy between primary human microglia and currently used microglial cell models and cell lines. In conclusion, we further delineated the unique and specific features that discriminate human microglia from other myeloid subsets, and we show that currently used cellular models only partly reflect the phenotype of primary human microglia. GLIA 2016;64:1857-1868.

  1. Mitochondria are involved in apoptosis induced by ultraviolet radiation in lepidopteran Spodoptera litura cell line

    Institute of Scientific and Technical Information of China (English)

    Shigang Shan; Kaiyu Liu; Jianxin Peng; Hanchao Yao; Yi Li; Huazhu Hong

    2009-01-01

    Mitochondria are involved in apoptosis of mammalian cells and even single-cell organisms, but mitochondria are not required in apoptosis in cultured Drosophila cells such as S2 and BG2 cell lines. It is not very clear whether mitochondria are involved in apoptosis in other insect cells such as lepidopteran cell lines. Thus, we determined to elucidate the role of mitochondria in apoptosis induced by ultraviolet radiation in Spodoptera litura (Lepidoptera: Noctuidae) cell line (SL-ZSU-1). The Western blot results suggested that cytochrome c in the ultraviolet-treated SL-1 cells was released from the mitochondria to cytosol as early as 4 h after the induction of ultraviolet radiation and increased in the cytosolic fractions in a time-dependent manner. Flow cytometric analysis of mitochondrial membrane potential (△Ψm) of SL-ZSU-1 cell treated with ultraviolet-C (UV-C) light indicated the decrease in mitochondrial membrane potential was dependent on the times of ultraviolet treatment. Both of them are different from apoptosis in cultured Drosophila melanogaster cell lines (S2 and BG2) and it appears evident mitochondria are involved in apoptosis of the studied lepidopteran cells.

  2. CUDA Enabled Graph Subset Examiner

    Energy Technology Data Exchange (ETDEWEB)

    2016-12-22

    Finding Godsil-McKay switching sets in graphs is one way to demonstrate that a specific graph is not determined by its spectrum--the eigenvalues of its adjacency matrix. An important area of active research in pure mathematics is determining which graphs are determined by their spectra, i.e. when the spectrum of the adjacency matrix uniquely determines the underlying graph. We are interested in exploring the spectra of graphs in the Johnson scheme and specifically seek to determine which of these graphs are determined by their spectra. Given a graph G, a Godsil-McKay switching set is an induced subgraph H on 2k vertices with the following properties: I) H is regular, ii) every vertex in G/H is adjacent to either 0, k, or 2k vertices of H, and iii) at least one vertex in G/H is adjacent to k vertices in H. The software package examines each subset of a user specified size to determine whether or not it satisfies those 3 conditions. The software makes use of the massive parallel processing power of CUDA enabled GPUs. It also exploits the vertex transitivity of graphs in the Johnson scheme by reasoning that if G has a Godsil-McKay switching set, then it has a switching set which includes vertex 1. While the code (in its current state) is tuned to this specific problem, the method of examining each induced subgraph of G can be easily re-written to check for any user specified conditions on the subgraphs and can therefore be used much more broadly.

  3. Almost Chebyshev set with respect to bounded subsets

    Institute of Scientific and Technical Information of China (English)

    李冲; 王兴华

    1997-01-01

    The uniqueness and existence of restricted Chebyshev center with respect to arbitrary subset are investigated. The concept of almost Chebyshev sets with respect to bounded subsets is introduced. It is proved that each closed subset in a reflexive locally uniformly convex (uniformly convex, respectively) Banach space is an almost Chebyshev subset with respect to compact convex subsets (bounded convex subsets and bounded subsets, respectively).

  4. Central nervous system involvement in T-cell lymphoma: A single center experience.

    Science.gov (United States)

    Gurion, Ronit; Mehta, Neha; Migliacci, Jocelyn C; Zelenetz, Andrew; Moskowitz, Alison; Lunning, Matthew; Moskowitz, Craig; Hamlin, Paul; Horwitz, Steven

    2016-05-01

    Background We characterized the incidence of central nervous system (CNS) involvement, risk factors and outcome in a large single institution dataset of peripheral T-cell lymphoma (PTCL). Methods Retrospective review of the PTCL database at Memorial Sloan Kettering Cancer Center. We identified 231 patients with any subtype of PTCL between 1994-2011 with a minimum six months of follow-up or an event defined as relapse or death. Results Histologies included peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) (31.6%), angioimmunoblastic (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK + (6.1%), extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL) (7.4%), and transformed mycosis fungoides (8.7%). Seventeen patients had CNS disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B-cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months (0.16-103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal methotrexate). Rates of CNS involvement were not different in patients who received prophylaxis. Univariate analysis identified stage III-IV, bone marrow involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On multivariate analysis, >1 extranodal site and international prognostic index (IPI) ≥ 3 were predictive for CNS involvement. The median survival of patients with CNS involvement was 2.63 months (0.10-75). Conclusions Despite high relapse rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with CNS involvement is poor and risk factors include: >1 extra nodal site and IPI ≥3.

  5. Involvement of the parasympathetic nervous system in the initiation of regeneration of pancreatic β-cells.

    Science.gov (United States)

    Medina, Anya; Yamada, Satoko; Hara, Akemi; Hamamoto, Kohei; Kojima, Itaru

    2013-01-01

    The mechanism that initiates regeneration of pancreatic β-cells is not clear at present. The vagal nerve is implicated in the regulation of gastrointestinal functions, glucose metabolism and proliferation of pancreatic β-cells under physiological conditions. To elucidate the triggering mechanism of the regeneration of pancreatic β-cells, we examined the involvement of the vagal nerve. To this end, we employed a rat pancreatic duct ligation (DL) model, in which profound β-cell neogenesis and β-cell proliferation were observed within a week. We administered atropine to block the vagal nerve. Administration of atropine inhibited proliferation of β-cells in both islets and islet-like cell clusters (ICC), without affecting ductal cell proliferation in the ligated pancreas. The numbers of PDX-1 and MafB-positive cells in or attaching to the ducts were significantly reduced by atropine. MafB/glucagon and MafB/insulin double-positive cells were also decreased by atropine. Finally, atropine reduced the number of MafA-positive ductal cells, all of which were positive for insulin, by 50% on day 5. These results strongly suggest that the vagal nerve is involved in β-cell proliferation, induction of endocrine progenitors and neogenesis of α- and β-cells.

  6. Involvement of hepatitis B X-interacting protein (HBXIP) in proliferation regulation of cells

    Institute of Scientific and Technical Information of China (English)

    Feng-ze WANG; Li SHA; Wei-ying ZHANG; Lian-ying WU; Ling QIAO; Nan LI; Xiao-dong ZHANG; Li-hong YE

    2007-01-01

    Aim: To investigat the effect of Hepatitis B X-interacting protein (HBXIP) on cell proliferation. Methods: A rabbit antibody against HBXIP was generated. The RNA interference (RNAi) fragment of the HBXIP gene was constructed in the pSilencer-3.0-H1 vector termed pSilencer-hbxip. Plasmids of the pcDNA3-hbxip encoding HBXIP gene and pSilencer-hbxip were transfected into human breast carcinoma MCF-7 cells, hepatoma H7402 cells, and the normal human hepatic cell line L-O2, respectively. 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bro- mide (MTT) assay and 5-bromo-2-deoxyuridine incorporation assay were applied to detect cell proliferation. MCF-7 cells and L-O2 cells in the cell cycle were examined by flow cytometry. The proteins involved in cell proliferation and cell cycle were investigated by Western blot. Results: Overexpression of HBXIP resulted in the promotion of proliferation of MCF-7, H7402, and L-O2 cells. Flow cytometry showed that the overexpression of HBXIP promoted the cell prolifera-tion of MCF-7 and L-O2 cells, and led to an increased cell proliferative index in MCF-7 cells (from 46.25% to 58.28%) and L-O2 cells (from 29.62% to 35.54%). Western blot showed that expression levels of c-Myc, Bcl-2, and proliferating cell nuclear antigen were upregulated in MCF-7, H7402, or L-O2 cells, whereas that of p27 was downregulated. However, the RNAi of HBXIP brought opposite results.Conclusion: One of the functions of HBXIP is its involvement in cell proliferation.

  7. Involvement of highly sulfated chondroitin sulfate in the metastasis of the Lewis lung carcinoma cells.

    NARCIS (Netherlands)

    Li, F.; Dam, G.B. ten; Murugan, S.; Yamada, S.; Hashiguchi, T.; Mizumoto, S.; Oguri, K.; Okayama, M.; Kuppevelt, A.H.M.S.M. van; Sugahara, K.

    2008-01-01

    The altered expression of cell surface chondroitin sulfate (CS) and dermatan sulfate (DS) in cancer cells has been demonstrated to play a key role in malignant transformation and tumor metastasis. However, the functional highly sulfated structures in CS/DS chains and their involvement in the process

  8. The Fas pathway is involved in pancreatic beta cell secretory function

    DEFF Research Database (Denmark)

    Schumann, Desiree M; Maedler, Kathrin; Franklin, Isobel

    2007-01-01

    Pancreatic beta cell mass and function increase in conditions of enhanced insulin demand such as obesity. Failure to adapt leads to diabetes. The molecular mechanisms controlling this adaptive process are unclear. Fas is a death receptor involved in beta cell apoptosis or proliferation, depending...

  9. 小儿脓毒症T细胞亚群变化分析及临床意义%Changes in T cell subsets in children with sepsis, and their clinical significance

    Institute of Scientific and Technical Information of China (English)

    袁远宏; 肖政辉; 张慧; 胥志跃; 罗海燕; 卢秀兰

    2013-01-01

    Objective To observe changes in T cell subsets in children with sepsis and their prognosis, and to investigate the clinical significance of these changes in the occurrence and development of sepsis. Methods Fifty children with severe sepsis and 150 children with general sepsis were enrolled as subjects, and 50 age-matched healthy children were included as controls. The percentages of CD3 + , CD4 + and CD8 + T cells in peripheral blood and CD4 + /CD8 + ratio were measured by flow cytometry. The pediatric critical illness score (PCIS) was calculated within 24 hours of admission. Results The children with severe sepsis showed significantly lower percentages of CD3 + , CD4+ and CD8+ T cells CD4 + /CD8+ ratio and PCIS than the controls and children with general sepsis (P < 0. 01). Among the 200 cases of sepsis, the percentages of CD3 + , CD4 + and CD8 + T cells, CD4 + /CD8 + ratio and PCIS were significantly lower in the cured group than in the deceased group. Conclusions Children with sepsis have different degrees of cellular immunosuppression, and the degree of cellular immunosuppression is significantly correlated with the severity of the disease. Detection of T cell subsets in peripheral blood is of great significance for evaluating immune function and judging disease severity in children with sepsis.%目的 通过观察脓毒症患儿T细胞亚群变化及预后,探讨其在脓毒症发生发展中的临床意义.方法 以50例严重脓毒症患儿和150例一般脓毒症患儿为研究对象,同时纳入50例非脓毒症儿童为对照组.采用流式细胞仪测定外周血CD3阳性淋巴细胞(CD3+T)、CD4阳性淋巴细胞(CD4+T)和CD8阳性淋巴细胞(CD8+ T)百分比及CD4+ T/CD8+T比值,并于入院24 h内行小儿危重病例评分(PCIS).结果 严重脓毒症组患儿CD3+T、CD4+T和CD8+T水平、CD4+ T/CD8+T比值及PCIS明显低于对照组及一般脓毒症组(P<0.01).200例脓毒症患儿中,治愈组CD3+T、CD4+T、CD8+T水平、CD4+ T/CD8+T

  10. Involvement of PACAP/ADNP signaling in the resistance to cell death in malignant peripheral nerve sheath tumor (MPNST) cells.

    Science.gov (United States)

    Castorina, Alessandro; Giunta, Salvatore; Scuderi, Soraya; D'Agata, Velia

    2012-11-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are sarcomas able to grow under conditions of metabolic stress caused by insufficient nutrients or oxygen. Both pituitary adenylate cyclase-activating polypeptide (PACAP) and activity-dependent neuroprotective protein (ADNP) have glioprotective potential. However, whether PACAP/ADNP signaling is involved in the resistance to cell death in MPNST cells remains to be clarified. Here, we investigated the involvement of this signaling system in the survival response of MPNST cells against hydrogen peroxide (H(2)O(2))-evoked death both in the presence of normal serum (NS) and in serum-starved (SS) cells. Results showed that ADNP levels increased time-dependently (6-48 h) in SS cells. Treatment with PACAP38 (10(-9) to 10(-5) M) dose-dependently increased ADNP levels in NS but not in SS cells. PAC(1)/VPAC receptor antagonists completely suppressed PACAP-stimulated ADNP increase and partially reduced ADNP expression in SS cells. NS-cultured cells exposed to H(2)O(2) showed significantly reduced cell viability (~50 %), increased p53 and caspase-3, and DNA fragmentation, without affecting ADNP expression. Serum starvation significantly reduced H(2)O(2)-induced detrimental effects in MPNST cells, which were not further ameliorated by PACAP38. Altogether, these finding provide evidence for the involvement of an endogenous PACAP-mediated ADNP signaling system that increases MPNST cell resistance to H(2)O(2)-induced death upon serum starvation.

  11. Extramedullary Involvement of Mast Cell Leukemia Detected by 18F-FDG PET/CT.

    Science.gov (United States)

    Fu, Zhanli; Zhang, Jin; Liu, Meng; Li, Ziao; Li, Qian

    2016-07-01

    Mast cell leukemia (MCL) is a very rare subtype of systemic mastocytosis, characterized by the leukemic expansion of immature mast cells. We present a case of MCL with extramedullary involvement of cervical lymph node and lung demonstrated by the initial F-FDG PET/CT scan. After a transient complete remission by induction chemotherapy and allogeneic hematopoietic stem cell transplantation, the follow-up PET/CT showed extensive extramedullary relapse involving multiple lymph nodes and small bowel. F-FDG PET/CT may be a useful tool to comprehensively stage and follow-up MCL.

  12. Transcription factors involved in the regulation of natural killer cell development and function: an update

    Directory of Open Access Journals (Sweden)

    Martha Elia Luevano

    2012-10-01

    Full Text Available Natural Killer (NK cells belong to the innate immune system and are key effectors in the immune response against cancer and infection. Recent studies have contributed to the knowledge of events controlling NK cell fate. The use of knockout mice has enabled the discovery of key transcription factors (TFs essential for NK cell development and function. Yet, unwrapping the downstream targets of these TFs and their influence on NK cells remains a challenge. In this review we discuss the latest TFs described to be involved in the regulation of NK cell development and maturation.

  13. The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses

    DEFF Research Database (Denmark)

    Blom, Lars H; Martel, Britta C; Larsen, Lau F

    2017-01-01

    BACKGROUND: The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim...... and ILC2 cells and basophils. In peanut-allergic subjects the peanut-specific Th2 (CD154(+) CRTh2(+) ) cells expressed more CD200R than the non-allergen specific Th2 (CD154(-) CRTh2(+) ) cells. Moreover, co-staining of CD161 and CD200R identified peanut-specific highly differentiated IL-4(+) IL-5(+) Th2...

  14. Protein micro patterned lattices to probe a fundamental lengthscale involved in cell adhesion

    CERN Document Server

    Guillou, Herve; Chaussy, Jacques; Block, Marc R

    2009-01-01

    Cell adhesion, a fundamental process of cell biology is involved in the embryo development and in numerous pathologies especially those related to cancers. We constrained cells to adhere on extracellular matrix proteins patterned in a micro lattices. The actin cytoskeleton is particularly sensitive to this constraint and reproducibly self organizes in simple geometrical patterns. Such highly organized cells are functional and proliferate. We performed statistical analysis of spread cells morphologies and discuss the existence of a fundamental lengthscale associated with active processes required for spreading.

  15. Adhesion of Human B Cells to Germinal Centers in Vitro Involves VLA-4 and INCAM-110

    Science.gov (United States)

    Freedman, Arnold S.; Munro, J. Michael; Rice, G. Edgar; Bevilacqua, Michael P.; Morimoto, Chikao; McIntyre, Bradley W.; Rhynhart, Kurt; Pober, Jordan S.; Nadler, Lee M.

    1990-08-01

    Human B lymphocytes localize and differentiate within the microenvironment of lymphoid germinal centers. A frozen section binding assay was developed for the identification of those molecules involved in the adhesive interactions between B cells and lymphoid follicles. Activated human B cells and B cell lines were found to selectively adhere to germinal centers. The VLA-4 molecule on the lymphocyte and the adhesion molecule INCAM-110, expressed on follicular dendritic cells, supported this interaction. This cellular interaction model can be used for the study of how B cells differentiate.

  16. Cancer stem cells from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall

    Directory of Open Access Journals (Sweden)

    Li Shengwen

    2012-09-01

    Full Text Available Abstract Background The cancer stem cell (CSC hypothesis posits that deregulated neural stem cells (NSCs form the basis of brain tumors such as glioblastoma multiforme (GBM. GBM, however, usually forms in the cerebral white matter while normal NSCs reside in subventricular and hippocampal regions. We attempted to characterize CSCs from a rare form of glioblastoma multiforme involving the neurogenic ventricular wall. Methods We described isolating CSCs from a GBM involving the lateral ventricles and characterized these cells with in vitro molecular biomarker profiling, cellular behavior, ex vivo and in vivo techniques. Results The patient’s MRI revealed a heterogeneous mass with associated edema, involving the left subventricular zone. Histological examination of the tumor established it as being a high-grade glial neoplasm, characterized by polygonal and fusiform cells with marked nuclear atypia, amphophilic cytoplasm, prominent nucleoli, frequent mitotic figures, irregular zones of necrosis and vascular hyperplasia. Recurrence of the tumor occurred shortly after the surgical resection. CD133-positive cells, isolated from the tumor, expressed stem cell markers including nestin, CD133, Ki67, Sox2, EFNB1, EFNB2, EFNB3, Cav-1, Musashi, Nucleostemin, Notch 2, Notch 4, and Pax6. Biomarkers expressed in differentiated cells included Cathepsin L, Cathepsin B, Mucin18, Mucin24, c-Myc, NSE, and TIMP1. Expression of unique cancer-related transcripts in these CD133-positive cells, such as caveolin-1 and −2, do not appear to have been previously reported in the literature. Ex vivo organotypic brain slice co-culture showed that the CD133+ cells behaved like tumor cells. The CD133-positive cells also induced tumor formation when they were stereotactically transplanted into the brains of the immune-deficient NOD/SCID mice. Conclusions This brain tumor involving the neurogenic lateral ventricular wall was comprised of tumor-forming, CD133-positive cancer

  17. Chemical -induced apoptotic cell death in tomato cells : involvement of caspase-like proteases

    NARCIS (Netherlands)

    Jong, de A.J.; Hoeberichts, F.A.; Yakimova, E.T.; Maximova, E.; Woltering, E.J.

    2000-01-01

    A new system to study programmed cell death in plants is described. Tomato (Lycopersicon esculentum Mill.) suspension cells were induced to undergo programmed cell death by treatment with known inducers of apoptosis in mammalian cells. This chemical-induced cell death was accompanied by the characte

  18. Pulmonary Langerhans Cell Histiocytosis with Lytic Bone Involvement in an Adult Smoker: Regression following Smoking Cessation

    Directory of Open Access Journals (Sweden)

    B. Routy

    2015-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare myeloid neoplasm characterized by the proliferation and dissemination of histiocytes. These in turn may cause symptoms ranging from isolated, infiltrative lesions to severe multisystem disease. Pulmonary Langerhans cell histiocytosis (PLCH presents as a localized polyclonal proliferation of Langerhans cells in the lungs causing bilateral cysts and fibrosis. In adults, this rare condition is considered a reactive process associated with cigarette smoking. Recently, clonal proliferation has been reported with the presence of BRAF V600E oncogenic mutation in a subset of PLCH patients. Spontaneous resolution was described; however, based on case series, smoking cessation remains the most effective way to achieve complete remission and prevent long term complications related to tobacco. Herein, we report the case of an adult woman with biopsy-proven PLCH presenting with thoracic (T8 vertebral bone destruction. Both the lung and the bone diseases regressed following smoking cessation, representing a rare case of synchronous disseminated PCLH with bone localization. This observation underscores the contribution of cigarette smoking as a systemic trigger of both pulmonary and extrapulmonary bone lesions. A review of similar cases in the literature is also presented.

  19. Pulmonary Langerhans Cell Histiocytosis with Lytic Bone Involvement in an Adult Smoker: Regression following Smoking Cessation

    Science.gov (United States)

    Routy, B.; Hoang, J.; Gruber, J.

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the proliferation and dissemination of histiocytes. These in turn may cause symptoms ranging from isolated, infiltrative lesions to severe multisystem disease. Pulmonary Langerhans cell histiocytosis (PLCH) presents as a localized polyclonal proliferation of Langerhans cells in the lungs causing bilateral cysts and fibrosis. In adults, this rare condition is considered a reactive process associated with cigarette smoking. Recently, clonal proliferation has been reported with the presence of BRAF V600E oncogenic mutation in a subset of PLCH patients. Spontaneous resolution was described; however, based on case series, smoking cessation remains the most effective way to achieve complete remission and prevent long term complications related to tobacco. Herein, we report the case of an adult woman with biopsy-proven PLCH presenting with thoracic (T8) vertebral bone destruction. Both the lung and the bone diseases regressed following smoking cessation, representing a rare case of synchronous disseminated PCLH with bone localization. This observation underscores the contribution of cigarette smoking as a systemic trigger of both pulmonary and extrapulmonary bone lesions. A review of similar cases in the literature is also presented. PMID:25789184

  20. NK ACTIVITY OF LYMPHOCYTE SUBSETS AND THE EFFECTS OF LOW DOSE RADIATION

    Institute of Scientific and Technical Information of China (English)

    S