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Sample records for cell subset involved

  1. The Exon Junction Complex Controls the Efficient and Faithful Splicing of a Subset of Transcripts Involved in Mitotic Cell-Cycle Progression.

    Science.gov (United States)

    Fukumura, Kazuhiro; Wakabayashi, Shunichi; Kataoka, Naoyuki; Sakamoto, Hiroshi; Suzuki, Yutaka; Nakai, Kenta; Mayeda, Akila; Inoue, Kunio

    2016-01-01

    The exon junction complex (EJC) that is deposited onto spliced mRNAs upstream of exon-exon junctions plays important roles in multiple post-splicing gene expression events, such as mRNA export, surveillance, localization, and translation. However, a direct role for the human EJC in pre-mRNA splicing has not been fully understood. Using HeLa cells, we depleted one of the EJC core components, Y14, and the resulting transcriptome was analyzed by deep sequencing (RNA-Seq) and confirmed by RT-PCR. We found that Y14 is required for efficient and faithful splicing of a group of transcripts that is enriched in short intron-containing genes involved in mitotic cell-cycle progression. Tethering of EJC core components (Y14, eIF4AIII or MAGOH) to a model reporter pre-mRNA harboring a short intron showed that these core components are prerequisites for the splicing activation. Taken together, we conclude that the EJC core assembled on pre-mRNA is critical for efficient and faithful splicing of a specific subset of short introns in mitotic cell cycle-related genes. PMID:27490541

  2. Effect of low-dose irradiation upon T cell subsets involved in the response of primed A/J mice to SaI cells

    International Nuclear Information System (INIS)

    A/Jax (A/J) mice primed to Sarcoma I (SaI) exhibit an augmented response in association with low-dose (0.15 Gy) irradiation. This phenomenon is best demonstrated in tumour neutralization (Winn assay) or cell transfer experiments utilizing mice depleted of thymus-derived (T) cells. It is particularly dependent upon the duration of priming and the growth characteristics of the tumour in the primary host. The importance of these two variables appears to relate to their influence upon the cell types responsible for the host response, and includes both an effector and a suppressor component. Radiation-induced inhibition of the suppressor component appears responsible for low-dose augmentation and results in injury to a T cell of the Lyt-1-2+ phenotype. In Winn assays employing equal numbers of immune spleen cells and SaI cells, the smallest tumours are associated with Lyt-1-positive (Lyt-1+2- and Lyt-1+2+) cells and exposure to 0.15 Gy markedly inhibits their anti-SaI activity. Thus, even though the effect is in the opposite direction, both the effector and suppressor components of the anti-SaI response in A/J mice are exceedingly radiosensitive. (author)

  3. Harnessing Human Dendritic Cell Subsets for Medicine

    Science.gov (United States)

    Ueno, Hideki; Schmitt, Nathalie; Klechevsky, Eynav; Pedroza-Gonzales, Alexander; Matsui, Toshimichi; Zurawski, Gerard; Oh, SangKon; Fay, Joseph; Pascual, Virginia; Banchereau, Jacques; Palucka, Karolina

    2010-01-01

    Summary Immunity results from a complex interplay between the antigen-nonspecific innate immune system and the antigen-specific adaptive immune system. The cells and molecules of the innate system employ non-clonal recognition receptors including lectins, Toll-like receptors, NOD-like receptors and helicases. B and T lymphocytes of the adaptive immune system employ clonal receptors recognizing antigens or their derived peptides in a highly specific manner. An essential link between innate and adaptive immunity is provided by dendritic cells (DCs). DCs can induce such contrasting states as immunity and tolerance. The recent years have brought a wealth of information on the biology of DCs revealing the complexity of this cell system. Indeed, DC plasticity and subsets are prominent determinants of the type and quality of elicited immune responses. Here we summarize our recent studies aimed at a better understanding of the DC system to unravel the pathophysiology of human diseases and design novel human vaccines. PMID:20193020

  4. Isolation of Human Skin Dendritic Cell Subsets.

    Science.gov (United States)

    Gunawan, Merry; Jardine, Laura; Haniffa, Muzlifah

    2016-01-01

    Dendritic cells (DCs) are specialized leukocytes with antigen-processing and antigen-presenting functions. DCs can be divided into distinct subsets by anatomical location, phenotype and function. In human, the two most accessible tissues to study leukocytes are peripheral blood and skin. DCs are rare in human peripheral blood (Nestle et al., J Immunol 151:6535-6545, 1993). These factors led to the extensive use of skin DCs as the "prototype" migratory DCs in human studies. In this chapter, we detail the protocols to isolate DCs and resident macrophages from human skin. We also provide a multiparameter flow cytometry gating strategy to identify human skin DCs and to distinguish them from macrophages. PMID:27142012

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

    Institute of Scientific and Technical Information of China (English)

    WANG JiongKun; XING FeiYue

    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.

  6. 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.

  7. Harnessing Human Dendritic Cell Subsets to Design Novel Vaccines

    Science.gov (United States)

    Banchereau, Jacques; Klechevsky, Eynav; Schmitt, Nathalie; Morita, Rimpei; Palucka, Karolina; Ueno, Hideki

    2009-01-01

    Summary Dendritic cells (DCs) orchestrate a repertoire of immune responses that endow resistance to infection and tolerance to self. DC plasticity and subsets are prominent determinants of the quality of elicited immune responses. Different DC subsets display different receptors and surface molecules, and express different sets of cytokines/chemokines, all of which lead to distinct immunological outcomes. Recent findings on human DC subsets and their functional specialization have provided insights for the design of novel human vaccines. PMID:19769733

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

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    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. Cancer stem cell subsets and their relationships

    OpenAIRE

    Pan Yi-Fei; Yang Han; Chen Chong; Liu Hai-Guang; Zhang Xiao-Hua

    2011-01-01

    Abstract Emerging evidence suggests that cancer stem cells account for the initiation and progression of cancer. While many types of cancer stem cells with specific markers have been isolated and identified, a variety of differences among them began to be appreciated. Cancer stem cells are hierarchical populations that consist of precancerous stem cells, primary cancer stem cells, migrating cancer stem cells and chemoradioresistant cancer stem cells, playing different roles in cancer initiati...

  10. Role of plasmacytoid dendritic cell subsets in allergic asthma

    OpenAIRE

    Maazi, Hadi; Lam, Jonathan; Lombardi, Vincent; Akbari, Omid

    2013-01-01

    Plasmacytoid dendritic cells (pDCs) are major type-I interferon producing cells that play important roles in antiviral immunity and tolerance induction. These cells share a common DC progenitor with conventional DCs and Fms-like tyrosine kinase-3 ligand is essential for their development. Several subsets of pDCs have been identified to date including CCR9+, CD9+ and CD2+ pDCs. Recently, three subsets of pDCs were described namely, CD8α−β−, CD8α+β− and CD8α+β+ subsets. Interestingly, CD8α+β− a...

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

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    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

  12. Sterile inflammation - do innate lymphoid cell subsets play a role?

    OpenAIRE

    Walsh, Patrick

    2012-01-01

    PUBLISHED The recent identification of several novel innate lymphoid cell (iLC) subsets has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets toward the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent st...

  13. Phenotypic Characterization of Five Dendritic Cell Subsets in Human Tonsils

    OpenAIRE

    Summers, Kelly L.; Hock, Barry D.; McKenzie, Judith L.; Hart, Derek N.J.

    2001-01-01

    Heterogeneous expression of several antigens on the three currently defined tonsil dendritic cell (DC) subsets encouraged us to re-examine tonsil DCs using a new method that minimized DC differentiation and activation during their preparation. Three-color flow cytometry and dual-color immunohistology was used in conjunction with an extensive panel of antibodies to relevant DC-related antigens to analyze lin− HLA-DR+ tonsil DCs. Here we identify, quantify, and locate five tonsil DC subsets bas...

  14. Targeting Human Dendritic Cell Subsets for Improved Vaccines

    Science.gov (United States)

    Ueno, Hideki; Klechevsky, Eynav; Schmitt, Nathalie; Ni, Ling; Flamar, Anne-Laure; Zurawski, Sandra; Zurawski, Gerard; Palucka, Karolina; Banchereau, Jacques; Oh, SangKon

    2011-01-01

    Summary Dendritic cells (DCs) were discovered in 1973 by Ralph Steinman as a previously undefined cell type in the mouse spleen and are now recognized as a group of related cell populations that induce and regulate adaptive immune responses. Studies of the past decade show that, both in mice and humans, DCs are composed of subsets that differ in their localization, phenotype, and functions. These progresses in our understanding of DC biology provide a new framework for improving human health. In this review, we discuss human DC subsets in the context of their medical applications, with a particular focus on DC targeting. PMID:21277223

  15. Human NK Cell Subset Functions Are Differentially Affected by Adipokines

    OpenAIRE

    Huebner, Lena; Engeli, Stefan; Christiane D Wrann; Goudeva, Lilia; Laue, Tobias; Kielstein, Heike

    2013-01-01

    Background: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines). Since natural killer (NK) cells are the host’s primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM) affects functions of two distinct human NK cell subsets. Methods: Isolated human peripheral blood mononuclear cell...

  16. Human NK cell subset functions are differentially affected by adipokines.

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    Lena Huebner

    Full Text Available BACKGROUND: Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines. Since natural killer (NK cells are the host's primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM affects functions of two distinct human NK cell subsets. METHODS: Isolated human peripheral blood mononuclear cells (PBMCs were cultured with various concentrations of human and murine ACM harvested on two different days during adipogenesis and analyzed by fluorescent-activated cell sorting (FACS. RESULTS: FACS analyses showed that the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, granzyme A (GzmA and interferon (IFN-γ in NK cells was regulated in a subset-specific manner. ACM treatment altered IFN-γ expression in CD56(dim NK cells. The production of GzmA in CD56(bright NK cells was differentially affected by the distinct adipokine compositions harvested at different states of adipogenesis. Comparison of the treatment with either human or murine ACM revealed that adipokine-induced effects on NK cell expression of the leptin receptor (Ob-R, TRAIL and IFN-γ were species-specific. CONCLUSION: Considering the growing prevalence of obesity and the various disorders related to it, the present study provides further insights into the roles human NK cell subsets play in the obesity-associated state of chronic low-grade inflammation.

  17. CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm.

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    Hirahara, Kiyoshi; Nakayama, Toshinori

    2016-04-01

    CD4(+)T cells are crucial for directing appropriate immune responses during host defense and for the pathogenesis of inflammatory diseases. In addition to the classical biphasic model of differentiation of T-helper 1 (Th1) and Th2 cells, unexpected increases in the numbers of CD4(+)T-cell subsets, including Th17, Th9, T follicular-helper (Tfh) and T-regulatory (Treg) cells, have been recognized. In the present review, we focus on how these various T-helper cell subsets contribute to the pathogenesis of immune-mediated inflammatory diseases. In particular, we focus on multiple sclerosis, psoriasis and asthma as typical model diseases in which multiple T-helper cell subsets have recently been suggested to play a role. We will also discuss various unique sub-populations of T-helper cells that have been identified. First, we will introduce the heterogeneous T-helper cell subsets, which are classified by their simultaneous expression of multiple key transcription factors. We will also introduce different kinds of memory-type Th2 cells, which are involved in the pathogenesis of chronic type-2 immune-related diseases. Finally, we will discuss the molecular mechanisms underlying the generation of the plasticity and heterogeneity of T-helper cell subsets. The latest progress in the study of T-helper cell subsets has forced us to reconsider the etiology of immune-mediated inflammatory diseases beyond the model based on the Th1/Th2 balance. To this end, we propose another model--the pathogenic T-helper population disease-induction model--as a possible mechanism for the induction and/or persistence of immune-mediated inflammatory diseases. PMID:26874355

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

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    Talwar, Avaneendra; Arun, K V; Kumar, T S S; Clements, Jasmine

    2013-05-01

    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. PMID:24049327

  19. Non-suppressive regulatory T cell subset expansion in pulmonary arterial hypertension.

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    Sada, Yoshiharu; Dohi, Yoshihiro; Uga, Sayuri; Higashi, Akifumi; Kinoshita, Hiroki; Kihara, Yasuki

    2016-08-01

    Regulatory T cells (Tregs) have been reported to play a pivotal role in the vascular remodeling of pulmonary arterial hypertension (PAH). Recent studies have revealed that Tregs are heterogeneous and can be characterized by three phenotypically and functionally different subsets. In this study, we investigated the roles of Treg subsets in the pathogenesis of PAH in eight patients with PAH and 14 healthy controls. Tregs and their subsets in peripheral blood samples were analyzed by flow cytometry. Treg subsets were defined as CD4(+)CD45RA(+)FoxP3(low) resting Tregs (rTregs), CD4(+)CD45RA(-)FoxP3(high) activated Tregs (aTregs), and CD4(+)CD45RA(-)FoxP3(low) non-suppressive Tregs (non-Tregs). The proportion of Tregs among CD4(+) T cells was significantly higher in PAH patients than in controls (6.54 ± 1.10 vs. 3.81 ± 0.28 %, p Tregs was significantly elevated in PAH patients compared with controls (4.06 ± 0.40 vs. 2.79 ± 0.14 %, p Tregs (p Treg subset was expanded and functionally activated in peripheral lymphocytes obtained from IPAH patients. We hypothesize that immunoreactions involving the specific activation of the non-Treg subset might play a role in the vascular remodeling of PAH. PMID:26319442

  20. Tachykinins stimulate a subset of mouse taste cells.

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    Jeff Grant

    Full Text Available The tachykinins substance P (SP and neurokinin A (NKA are present in nociceptive sensory fibers expressing transient receptor potential cation channel, subfamily V, member 1 (TRPV1. These fibers are found extensively in and around the taste buds of several species. Tachykinins are released from nociceptive fibers by irritants such as capsaicin, the active compound found in chili peppers commonly associated with the sensation of spiciness. Using real-time Ca(2+-imaging on isolated taste cells, it was observed that SP induces Ca(2+ -responses in a subset of taste cells at concentrations in the low nanomolar range. These responses were reversibly inhibited by blocking the SP receptor NK-1R. NKA also induced Ca(2+-responses in a subset of taste cells, but only at concentrations in the high nanomolar range. These responses were only partially inhibited by blocking the NKA receptor NK-2R, and were also inhibited by blocking NK-1R indicating that NKA is only active in taste cells at concentrations that activate both receptors. In addition, it was determined that tachykinin signaling in taste cells requires Ca(2+-release from endoplasmic reticulum stores. RT-PCR analysis further confirmed that mouse taste buds express NK-1R and NK-2R. Using Ca(2+-imaging and single cell RT-PCR, it was determined that the majority of tachykinin-responsive taste cells were Type I (Glial-like and umami-responsive Type II (Receptor cells. Importantly, stimulating NK-1R had an additive effect on Ca(2+ responses evoked by umami stimuli in Type II (Receptor cells. This data indicates that tachykinin release from nociceptive sensory fibers in and around taste buds may enhance umami and other taste modalities, providing a possible mechanism for the increased palatability of spicy foods.

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

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    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. PMID:27178467

  2. Regulatory T cells subsets in filarial infection and their function

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    Simon eMetenou

    2013-09-01

    Full Text Available Filarial infections in humans are chronic infections that cause significant morbidity. The chronic nature of these infections with continuous antigen release is associated with a parasite-specific T cell hypo-responsiveness that may over time also affect the immune responses to bystander antigens. Previous studies have shown the filarial parasite antigen-specific T cells hypo-responsiveness is mediated by regulatory cytokines -- IL-10 and TGF-β in particular. Recent studies have suggested that the modulated/regulated T cell responses associated with patent filarial infection may reflect an expansion of regulatory T cells (Tregs that include both Tregs induced in peripheral circulation or pTregs and the thymus-derived Tregs or tTregs. Although much is known about the phenotype of these regulatory populations, the mechanisms underlying their expansion and their mode of action in filarial and other infections remain unclear. Nevertheless there are data to suggest that while many of these regulatory cells are activated in an antigen-specific manner the ensuing effectors of this activation are relatively non-specific and may affect a broad range of immune cells. This review will focus on the subsets and function of regulatory T cells in filarial infection.

  3. Study of T cell subsets in patients with chronic glomerulonephritis by immuno-labelling technique

    International Nuclear Information System (INIS)

    As the developing of nuclear industry science, the possibility of nuclear radiation has increased rapidly. Treatments of diseases caused by radiation, especially acute radiation injury, rely heavily on bone marrow transplantation. The usage of immunology inhibitors is crucial to successfully carrying out bone marrow transplantation. So it is important to find out and research on immunology inhibitors. Using the changes of T cell subsets as a marker of immunology function before and after treatment of chronic glomerulonephritis, the authors observed the effect of Tripterygium wilfordii (TW)--an Chinese traditional drug which may probably become an important immunology inhibitor--on the treatment of chronic glomerulonephritis. Methods: immuno-labelling technique was used to measure the changes of T cell subsets in 77 CGN patients before and after treated with TW. Results: CD3+ and CD4+ cells in CGN patients were lower than those in healthy control (p + to CD8+ (CD4+/CD8+) cells reduced significantly (p+, CD4+ cells and the ratio of CD4+/CD8+ in most of the patients with CGN were further reduced. In patients with uremia, only CD3+ cell level was lower than the level before treatment, while the ratio of CD4+ to CD8+ (CD4+/CD8+) did not change markedly. Conclusion: The imbalance of various T cell subsets and dysfunction of these T cells may play an important role in the pathogenesis of CGN. the increase in γδT cells may be related with the development of CGN. The pharmacological mechanism of TW in the treatment of CGN patients may involve regulation of balance of T cell subsets and inhibition of the T helper functions

  4. 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.

  5. Subsets of regulatory T cells and their roles in allergy.

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    Zhang, Huiyun; Kong, Hui; Zeng, Xiaoning; Guo, Lianyi; Sun, Xiaoyun; He, Shaoheng

    2014-01-01

    In recent years, it is recognized that acquired immunity is controlled by regulatory T cell (Treg). Since fundamental pathophysiological changes of allergy are mainly caused by hyperresponsiveness of immune system to allergens that acquires after birth, Tregs likely play key roles in the pathogenesis of allergy, particularly during the sensitization phase. However, accumulated information indicate that there are several distinctive subtypes of Tregs in man, and each of them seems to play different role in controlling immune system, which complicates the involvement of Tregs in allergy. The aim of the present study is to attempt to classify subtypes of Tregs and summarize their roles in allergy. Tregs should include natural Tregs (nTreg) including inducible costimulator (ICOS)(+) Tregs, inducible/adaptive Tregs (iTreg), interleukin (IL)-10-producing type 1 Tregs (Tr1 cells), CD8(+) Tregs and IL-17-producing Tregs. These cells share some common features including expression of Foxp3 (except for Tr1 cells), and secretion of inhibitory cytokine IL-10 and/or TGF-β. Furthermore, it is noticeable that Tregs likely contribute to allergic disorders such as dermatitis and airway inflammation, and play a crucial role in the treatment of allergy through their actions on suppression of effector T cells and inhibition of activation of mast cells and basophils. Modulation of functions of Tregs may provide a novel strategy to prevent and treat allergic diseases. PMID:24886492

  6. Cross-presentation of cell-associated antigens by MHC class I in dendritic cell subsets

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    Enric eGutiérrez-Martínez

    2015-07-01

    Full Text Available Dendritic cells have the unique ability to pick up dead cells carrying antigens in tissue and migrate to the lymph nodes where they can cross-present cell-associated antigens by MHC class I to CD8+ T cells. There is strong in vivo evidence that the mouse XCR1+ dendritic cells subset acts as a key player in this process. The intracellular processes underlying cross-presentation remain controversial and several pathways have been proposed. Indeed, a wide number of studies have addressed the cellular process of cross-presentation in vitro using a variety of sources of antigen and antigen presenting cells. Here we review the in vivo and in vitro evidence supporting the current mechanistic models and disscuss their physiological relevance to the cross-presentation of cell-associated antigens by dendritic cells subsets

  7. Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma

    OpenAIRE

    Sato, Yusuke; Shimizu, Kanako; Shinga, Jun; Hidaka, Michihiro; Kawano, Fumio; Kakimi, Kazuhiro; Yamasaki, Satoru; Asakura, Miki; Fujii, Shin-ichiro

    2015-01-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population with the ability to suppress immune responses and are currently classified into three distinct MDSC subsets: monocytic, granulocytic and non-monocytic, and non-granulocytic MDSCs. Although NK cells provide an important first-line defense against newly transformed cancer cells, it is unknown whether NK cells can regulate MDSC populations in the context of cancer. In this study, we initially found that the frequency of MDSC...

  8. Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo

    OpenAIRE

    Yadav, Mahesh; Louvet, Cedric; Davini, Dan; Gardner, James M.; Martinez-Llordella, Marc; Bailey-Bucktrout, Samantha; Anthony, Bryan A.; Sverdrup, Francis M; Head, Richard; Kuster, Daniel J.; Ruminski, Peter; Weiss, David; von Schack, David; Bluestone, Jeffrey A.

    2012-01-01

    Foxp3+ CD4+ T helper cells called regulatory T (T reg) cells play a key role in controlling reactivity to self-antigens and onset of autoimmunity. T reg cells either arise in thymus and are called natural T reg (nT reg) cells or are generated in the periphery through induction of Foxp3 and are called inducible T reg (iT reg) cells. The relative contributions of iT reg cells and nT reg cells in peripheral tolerance remain unclear as a result of an inability to separate these two subsets of T r...

  9. mIL-2R, T cell subsets and hepatitis C

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

    2002-01-01

    AIM: To study the levels of membrane interleukin-2 receptor (mIL-2R) and T cell subsets in peripheral blood mononuclear cells (PBMC) from patients with hepatitis C and their role in the pathogenesis of hepatitis C.

  10. TCR repertoire and Foxp3 expression define functionally distinct subsets of CD4+ Treg cells1

    OpenAIRE

    Kuczma, Michal; Pawlikowska, Iwona; Kopij, Magdalena; Podolsky, Robert; Rempala, Grzegorz A.; Kraj, Piotr

    2009-01-01

    Despite extensive research efforts to characterize peripheral regulatory T cells (Treg) expressing transcription factor Foxp3, their subset complexity, phenotypic characteristics, TCR repertoire and antigen specificities remain ambiguous. Here, we identify and define two subsets of peripheral Treg cells differing in Foxp3 expression level and TCR repertoires. Treg cells expressing a high level of Foxp3 and TCRs not utilized by naive CD4+ T cells present a stable suppressor phenotype and domin...

  11. 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.

  12. 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.

  13. 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.

  14. CXCR4-positive subset of glioma is enriched for cancer stem cells.

    Science.gov (United States)

    Zheng, Xuesheng; Xie, QingSong; Li, Shiting; Zhang, Wenchuan

    2011-01-01

    CXC chemokine receptor 4 (CXCR4) is a cell surface molecule expressed in a distinct subset of glioma cells with enhanced tumorigenicity, and it is related to many important biological activities of the tumor. We supposed that this receptor might be a cell surface "marker" for glioma stem cells. This hypothesis was tested both in vitro and in vivo. The CXCR4+ and CXCR4- subsets were sorted from three human malignant glioma specimens. They were tested for the capability of colony formation in soft agar, generation of tumorosphere, self-renewal, and multipotent differentiation in vitro, and the capability of xenograft tumor in vivo. Drug and radiation resistance and coexpression with CD133 were studied for each subset. CXCR4+ glioma cells, but not CXCR4- cells, were capable of generating tumorospheres in serum-free medium. In addition, these spheres were able to self-renew after passage, and had multipotent differentiation after being induced in serum-containing medium. In soft agar assay, CXCR4+ cells generate much more colonies. The animal experiment revealed that CXCR4+ subpopulation had stronger tumorigenicity than the unsorted parental glioma cells, while the CXCR4- cells did not generate xenograft tumor. CXCR4-possitive cells were more resistant to temozolomide and radiation treatment. Both CXCR4+ and CXCR4- subsets contained very few CD133+ cells. The CXCR4+ subsets of glioma cells fulfill the standard of "cancer stem cell". PMID:22812188

  15. A human dendritic cell subset receptive to the Venezuelan equine encephalitis virus-derived replicon particle constitutively expresses IL-32.

    Science.gov (United States)

    Nishimoto, Kevin P; Laust, Amanda K; Nelson, Edward L

    2008-09-15

    Dendritic cells (DCs) are a diverse population with the capacity to respond to a variety of pathogens. Because of their critical role in pathogenesis and Ag-specific adaptive immune responses, DCs are the focus of extensive study and incorporation into a variety of immunotherapeutic strategies. The diversity of DC subsets imposes a substantial challenge to the successful development of DC-based therapies, requiring identification of the involved subset(s) and the potential roles each contributes to the immunologic responses. The recently developed and promising Venezuelan equine encephalitis replicon particle (VRP) vector system has conserved tropism for a subset of myeloid DCs. This immunotherapeutic vector permits in situ targeting of DCs; however, it targets a restricted subset of DCs, which are heretofore uncharacterized. Using a novel technique, we isolated VRP-receptive and -nonreceptive populations from human monocyte-derived DCs. Comparative gene expression analysis revealed significant differential gene expression, supporting the existence of two distinct DC populations. Further analysis identified constitutive expression of the proinflammatory cytokine IL-32 as a distinguishing characteristic of VRP-receptive DCs. IL-32 transcript was exclusively expressed (>50 fold) in the VRP-receptive DC population relative to the background level of expression in the nonreceptive population. The presence of IL-32 transcript was accompanied by protein expression. These data are the first to identify a subset of immature monocyte-derived DCs constitutively expressing IL-32 and they provide insights into both DC biology and potential mechanisms employed by this potent vector system. PMID:18768856

  16. Monitoring B cell subsets and alloreactivity in kidney transplantation

    OpenAIRE

    Crespo Barrio, Marta; Heidtc, Sebastiaan; Redondo Pach??n, Mar??a Dolores; Pascual Santos, Julio

    2015-01-01

    B cells are the precursors of antibody producing plasma cells that can give rise to the formation of donor-specific antibodies. However, recent data suggest that besides their role in antibody production, B cells participate in antibody-independent responses, potentially leading to allograft rejection or allograft tolerance. The presence of CD20+ B cells in kidney graft biopsies has been shown during severe acute rejection episodes and during chronic rejection. Furthermore, operationally tole...

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

    Directory of Open Access Journals (Sweden)

    ElenaVGalkina

    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.

  18. 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.

  19. 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 cytokines...... leads to subclinical or mild infections. In mice, an infection leads to a polarisation of either Th1 or Th2 Leishmania antigen specific cells. In contrast, both Th1 and Th2 Leishmania antigen specific cells can be identified in humans cured from L. donovani infections. Theoretically, Th1 cells and Th2...

  20. Sorting through subsets: Which T cell populations mediate highly effective adoptive immunotherapy?

    Science.gov (United States)

    Klebanoff, Christopher A.; Gattinoni, Luca; Restifo, Nicholas P.

    2012-01-01

    CD8+ T cells have been described as being naïve (TN) or one of four antigen-experienced subtypes representing a continuum of differentiation and maturation: stem cell memory (TSCM), central memory (TCM), effector memory (TEM), and terminally differentiated effector T cells (TEFF). In mice, adoptive cell transfer (ACT) of less differentiated TN, TSCM and TCM subsets have consistently demonstrated superior in vivo expansion, persistence, and antitumor capacities relative to the more differentiated TEM and TEFF cells. Retrospective analyses from human ACT trials have confirmed that transfer of less differentiated T cell subsets is highly correlated with objective clinical responses. These findings, combined with the recent ability to convey de novo antigen reactivity with high efficiency through genetic engineering of exogenous T cell or chimeric antigen receptors, now challenge the field with three important questions: 1) how should less differentiated T cell subsets be isolated for human clinical trials?; 2) what is the best means of expanding T cells ex vivo in such a way as to not corrupt the beneficial traits of the younger subsets?; and 3) is it necessary to physically separate younger subsets from their more differentiated counterparts? Answering these questions will allow for the rational development of the next generation of highly effective and potentially curative T cell therapies for the treatment of cancer. PMID:23090074

  1. CD163 positive subsets of blood dendritic cells

    DEFF Research Database (Denmark)

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

    CD163 and CD91 are scavenging receptors with highly increased expression during the differentiation of monocytes into the anti-inflammatory macrophage phenotype. In addition, CD91 is expressed in monocyte-derived dendritic cells (MoDCs), where the receptor is suggested to be important for...... internalization of CD91-targeted antigens to be presented on the dendritic cell surface for T-cell stimulation. Despite their overlap in functionality, the expression of CD91 and CD163 has never been compared and the expression of CD163 in the monocyte-dendritic cell lineage is not yet characterized. CD163...... 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...

  2. B-cell subsets, signaling and their roles in secretion of autoantibodies.

    Science.gov (United States)

    Iwata, S; Tanaka, Y

    2016-07-01

    B cells play a pivotal role in the pathogenesis of autoimmune diseases. In patients with systemic lupus erythematosus (SLE), the percentages of plasmablasts and IgD(-)CD27(-) double-negative memory B cells in peripheral blood are significantly increased, while IgD(+)CD27(+) IgM memory B cells are significantly decreased compared to healthy donors. The phenotypic change is significantly associated with disease activity and concentration of autoantibodies. Treatment of B-cell depletion using rituximab results in the reconstitution of peripheral B cells in SLE patients with subsequent improvement in disease activity. Numerous studies have described abnormalities in B-cell receptor (BCR)-mediated signaling in B cells of SLE patients. Since differences in BCR signaling are considered to dictate the survival or death of naïve and memory B cells, aberrant BCR signal can lead to abnormality of B-cell subsets in SLE patients. Although Syk and Btk function as key molecules in BCR signaling, their pathological role in SLE remains unclear. We found that Syk and Btk do not only transduce activation signal through BCR, but also mediate crosstalk between BCR and Toll-like receptor (TLR) as well as BCR and JAK-STAT pathways in human B cells in vitro. In addition, pronounced Syk and Btk phosphorylation was observed in B cells of patients with active SLE compared to those of healthy individuals. The results suggest the involvement of Syk and Btk activation in abnormalities of BCR-mediated signaling and B-cell phenotypes during the pathological process of SLE and that Syk, Btk and JAK are potential therapeutic targets in SLE. PMID:27252261

  3. A subset of mouse colonic goblet cells expresses the bitter taste receptor Tas2r131.

    Directory of Open Access Journals (Sweden)

    Simone Prandi

    Full Text Available The concept that gut nutrient sensing involves taste receptors has been fueled by recent reports associating the expression of taste receptors and taste-associated signaling molecules in the gut and in gut-derived cell lines with physiological responses induced by known taste stimuli. However, for bitter taste receptors (Tas2rs, direct evidence for their functional role in gut physiology is scarce and their cellular expression pattern remained unknown. We therefore investigated Tas2r expression in mice. RT-PCR experiments assessed the presence of mRNA for Tas2rs and taste signaling molecules in the gut. A gene-targeted mouse strain was established to visualize and identify cell types expressing the bitter receptor Tas2r131. Messenger RNA for various Tas2rs and taste signaling molecules were detected by RT-PCR in the gut. Using our knock-in mouse strain we demonstrate that a subset of colonic goblet cells express Tas2r131. Cells that express this receptor are absent in the upper gut and do not correspond to enteroendocrine and brush cells. Expression in colonic goblet cells is consistent with a role of Tas2rs in defense mechanisms against potentially harmful xenobiotics.

  4. Histamine modulates multiple functional activities of monocyte-derived dendritic cell subsets via histamine receptor 2.

    Science.gov (United States)

    Simon, Tünde; Gogolák, Péter; Kis-Tóth, Katalin; Jelinek, Ivett; László, Valéria; Rajnavölgyi, Eva

    2012-02-01

    Expression of CD1a proteins in human monocyte-derived dendritic cells (DCs) specifies functionally distinct subsets with different inflammatory properties. Histamine is recognized as an inflammatory mediator released by various cell types including DCs. The diverse biological effects of histamine are mediated by G-protein-coupled histamine receptors (HRs), which are able to modulate the functional activities of DC subsets. The goal of the present study was to compare the expression and activity of HRs in the CD1a(-) and CD1a(+) monocyte-derived DC subsets and to test the effects of histamine on the differentiation, activation and functional activities of these subsets. We show that H2R is present at high levels in both DC subsets, whereas H1R and H4R are expressed in a subset-specific manner. Histamine shifts DC differentiation to the development of CD1a(-) DCs and modulates DC activation through its inhibitory effect on CD1a(+) DC differentiation. Histamine-induced reduction of CD1a(+) DCs is associated with increased secretion of IL-6 and IL-10, up-regulation of a typical combination of chemokines, expression C5aR1 by the CD1a(-) DC subset and enhanced migration of both activated DC subsets supported by the production of MMP-9 and MMP-12 enzymes. All these effects were shown to be mediated in a H2R-specific manner as revealed by the specific antagonist of the receptor. As H2R is expressed at high levels in both DC subsets, we propose that it may dominate the regulation of multiple DC functions. In contrast, H1R and H4R with opposing subset-related expression may have a regulatory or fine-tuning role in histamine-induced functional activities. PMID:22232416

  5. 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

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

    Science.gov (United States)

    Cron, Andrew; Gouttefangeas, Cécile; Frelinger, Jacob; Lin, Lin; Singh, Satwinder K; Britten, Cedrik M; Welters, Marij J P; van der Burg, Sjoerd H; West, Mike; Chan, Cliburn

    2013-01-01

    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 consistent labeling

  7. Subsets of regulatory T cells and their roles in allergy

    OpenAIRE

    ZHANG, HUIYUN; Kong, Hui; Zeng, Xiaoning; Guo, Lianyi; Sun, Xiaoyun; He, Shaoheng

    2014-01-01

    In recent years, it is recognized that acquired immunity is controlled by regulatory T cell (Treg). Since fundamental pathophysiological changes of allergy are mainly caused by hyperresponsiveness of immune system to allergens that acquires after birth, Tregs likely play key roles in the pathogenesis of allergy, particularly during the sensitization phase. However, accumulated information indicate that there are several distinctive subtypes of Tregs in man, and each of them seems to play diff...

  8. Sterile inflammation – do innate lymphoid cell subsets play a role?

    OpenAIRE

    Shane E Russell; Walsh, Patrick T.

    2012-01-01

    The recent identification of several novel innate lymphoid cell (iLC) subsets has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets toward the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent studies have hi...

  9. Sterile Inflammation-Do innate lymphoid cell subsets play a role?

    OpenAIRE

    Shane E Russell; Walsh, Patrick T.

    2012-01-01

    The recent identification of several novel innate lymphoid cell subsets (iLCs) has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets towards the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent studies have ...

  10. 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.

  11. 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. PMID:26999211

  12. Comparison of the quantities and subset distributions of natural killer cells among different races

    Institute of Scientific and Technical Information of China (English)

    FENG Yan-meng; ZHANG Rui-jun; ZHU Hong; PENG Hong; ZHOU Xiao-ping; HONG Kun-xue; LIU Jian-li; CHEN Jian-ping; SHAO Yi-ming

    2010-01-01

    Background Natural killer (NK) cells play critical roles in host immune defense, while the quantities and subset distributions may vary among different races. To address the difference, we compared these variables among Chinese Han, the Caucasians and the Blacks. The study may provide critical background information for both basic research and clinical investigation.Methods Blood samples collected from populations of different races were tested within 12 hours after collection and subsets of NK cells were characterized using flow cytometry.Results The absolute NK count in the Chinese Han was significantly higher than that in the Caucasian. The Han and Caucasian groups showed higher percentages of cytotoxic subset compared to that of the Black group. The percentage of cytokine-producing subset of Chinese Han group was lower than that of Caucasian and Black groups. Black group had a higher percentage of function-unknown NK subset than that of the Hah and Caucasian groups.Conclusion Our data indicated that NK cell count and the distribution of different subsets varied among different races,which should be taken into consideration in related investigations.

  13. Functional analysis of different haematopoietic stem cell subsets

    OpenAIRE

    Chawla R

    2009-01-01

    RÉSUMÉ : Elucider les bases moléculaires et cellulaires du fonctionnement des cellules souches s'avère crucial dans la compréhension de l'organisation cellulaire au sein des tissus et des organes ainsi que pour le développement de nouvelles stratégies thérapeutiques en médecine régénérative et en oncologie. Les cellules souches adultes les mieux connues sont celles responsables de l'hématopoïèse, les cellules souches hématopoïétiques (CSH). Durant ces dernières années, la recherche a porté un...

  14. Contribution of T Cell Subsets to the Pathophysiology of Pneumocystis-Related Immunorestitution Disease

    OpenAIRE

    Samir P Bhagwat; Gigliotti, Francis; Xu, Haodong; Wright, Terry W.

    2006-01-01

    Immune-mediated lung injury is an important component of Pneumocystis pneumonia (PcP)-related immunorestitution disease (IRD). However, the individual contribution of CD4+ and CD8+ T cells to the pathophysiology of IRD remains undetermined. Therefore, IRD was modeled in severe combined immunodeficient mice, and specific T cell depletion was used to determine how T cell subsets interact to affect the nature and severity of disease. CD4+ cells were more abundant than CD8+ cells during the acute...

  15. CD27 natural killer cell subsets play different roles during the pre-onset stage of experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Gao, Ming; Yang, Yan; Li, Daling; Ming, Bingxia; Chen, Huoying; Sun, Yan; Xiao, Yifan; Lai, Lin; Zou, Huijuan; Xu, Yong; Xiong, Ping; Tan, Zheng; Gong, Feili; Zheng, Fang

    2016-08-01

    NK cells participate in the development of human multiple sclerosis (MS) and mouse experimental autoimmune encephalomyelitis (EAE), but the roles of different NK cell subsets in disease onset remain poorly understood. In this study, murine NK cells were divided into CD27(high) and CD27(low/-) subsets. The CD27(high) subset was decreased and the CD27(low/-) subset was increased in lymphoid organs during the pre-onset stage of EAE. Compared with the counterpart in naïve mice, the CD27(high) subset showed lower expression of Ly49D, Ly49H and NKG2D, and less production of IFN-γ, whereas the CD27(low/-) subset showed similar expression of the above mentioned surface receptors but higher cytotoxic activity in EAE mice. Compared with the CD27(high) subset, the CD27(low/-) subset exhibited increased promotion of DC maturation and no significant inhibition of T cells proliferation and Th17 cells differentiation in vitro Additionally, adoptive transfer of the CD27(low/-) subset, but not the CD27(high) subset, exacerbated the severity of EAE. Collectively, our data suggest the CD27 NK cell subsets play different roles in controlling EAE onset, which provide a new understanding for the regulation of NK cell subsets in early autoimmune disease. PMID:27368310

  16. Unique Eomes+ NK cell subsets are present in uterus and decidua during early pregnancy

    Directory of Open Access Journals (Sweden)

    Elisa eMontaldo

    2016-01-01

    Full Text Available Decidual and uterine Natural Killer (NK cells have been shown to contribute to the successful pregnancy both in humans and mice. NK cells represent cytotoxic group 1 innate lymphoid cells (ILCs and are distinct from the recently described helper ILC1. Here we show that both in humans and mice the majority of group 1 ILC in endometrium/uterus and decidua express Eomesodermin (Eomes, thus suggesting that they are developmentally related to conventional NK cells. However, they differed from peripheral NK cells. In humans Eomes+ decidual NK cells expressed CD49a and other markers of tissue residency including CD103, integrin β7, CD9, and CD69. The expression of CD103 allows the identification of different subsets of IFNγ-producing Eomes+ NK cells. We show that TGFβ can sustain/induce CD103 and CD9 expression in decidual NK cells and decidual CD34-derived NK cells, indicating that the decidual microenvironment can instruct the phenotype of Eomes+ NK cells.In murine decidua and uterus, Eomes+ cells included CD49a-CD49b+ conventional NK cells and CD49a+ cells. Notably, Eomes+CD49a+cells were absent in spleen and liver. Decidual and uterine Eomes+CD49a+ cells could be dissected in two peculiar cell subsets according to CD49b expression. CD49a-CD49b+ cells are enriched in mature CD11bhighCD27low cells, while CD49a+CD49b- and CD49a+CD49b+ cells contain higher percentages of immature CD11blowCD27high cells, both in uterus and decidua. Moreover, Eomes+CD49a+CD49b- cells decrease during gestation, thus suggesting that this peculiar subset may be required in early pregnancy rather than on later phases. Conversely, a minor Eomes-CD49a+ ILC1 population present in decidua and uterus increases during pregnancy. CD49b-Eomes+/- cells produce mainly TNF, while CD49a-CD49b+ conventional NK cells and CD49a+CD49b+ cells produce both IFNγ and TNF. Thus, human and murine decidua contains unique subsets of group 1 ILCs, including Eomes+ and Eomes- cells, with peculiar

  17. Subsets of Myeloid-Derived Suppressor Cells in Tumor Bearing Mice1

    OpenAIRE

    Youn, Je-in; Nagaraj, Srinivas; Collazo, Michelle; Gabrilovich, Dmitry I.

    2008-01-01

    Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of cells that play a critical role in tumor associated immune suppression. In an attempt to identify a specific subset of MDSC primarily responsible for immunosuppressive features of these cells, 10 different tumor models were investigated. All models showed variable but significant increase in the population of MDSC. Variability of MDSC expansion in vivo matched closely the effect of tumor-cell condition media (TCCM) in vitro....

  18. In human alloreactive CD4+ T-cells, dichloroacetate inhibits aerobic glycolysis, induces apoptosis and favors differentiation towards the regulatory T-cell subset instead of effector T-cell subsets.

    Science.gov (United States)

    Eleftheriadis, Theodoros; Sounidaki, Maria; Pissas, Georgios; Antoniadi, Georgia; Liakopoulos, Vassilios; Stefanidis, Ioannis

    2016-04-01

    Although kidney transplantation is the best therapy for end-stage renal disease, rejection remains a concern, and currently available immunosuppressive agents contribute to morbidity and mortality. Thus, novel immunosuppressive drugs are required. Dichloroacetate (DCA) is already used in the treatment of congenital lactic acidosis and characterized by limited toxicity. As DCA inhibits aerobic glycolysis, which is a prerequisite for CD4+ T-cell proliferation and differentiation into effector T-cells, its possible immunosuppressive role in mixed lymphocyte reaction (MLR), a model of alloreactivity, was investigated. Glucose and lactate concentrations were measured in the supernatants, and cell proliferation was assessed immunoenzymatically. CD4+ T‑cells were then isolated from the MLRs and the expression of cleaved caspase‑3, various enzymes involved in glycolysis, and the signature transcription factors of CD4+ T‑cell subsets were evaluated by western blotting. In MLRs, DCA decreased glucose consumption and aerobic glycolysis, while it exerted a negligible effect on cell proliferation. In CD4+ T‑cells, DCA induced apoptosis, and decreased the expression of glucose trasporter‑1, hexokinase II, lactate dehydrogenase‑A and phosphorylated pyruvate dehydrogenase, while it increased total pyruvate dehydrogenase. In addition, DCA increased the expression of transcription factor forkhead box P3, whereas it decreased the expression of T‑box transcription factor TBX21, trans‑acting T-cell-specific transcription factor GATA‑3 and retinoic acid receptor related orphan receptor‑γt. In conclusion, in alloreactive CD4+ T‑cells, DCA inhibits aerobic glycolysis, induces apoptosis and favors differentiation towards the regulatory T‑cell subset. These characteristics render it a promising immunosuppressive agent in the field of transplantation. PMID:26935268

  19. T-cell Subsets in Peripheral Blood and Tumors of Patients Treated With Oncolytic Adenoviruses

    Science.gov (United States)

    Kristian, Taipale; Ilkka, Liikanen; Juuso, Juhila; Aila, Karioja-Kallio; Minna, Oksanen; Riku, Turkki; Nina, Linder; Johan, Lundin; Ari, Ristimäki; Anna, Kanerva; Anniina, Koski; Timo, Joensuu; Markus, Vähä-Koskela; Akseli, Hemminki

    2015-01-01

    The quality of the antitumor immune response is decisive when developing new immunotherapies for cancer. Oncolytic adenoviruses cause a potent immunogenic stimulus and arming them with costimulatory molecules reshapes the immune response further. We evaluated peripheral blood T-cell subsets of 50 patients with refractory solid tumors undergoing treatment with oncolytic adenovirus. These data were compared to changes in antiviral and antitumor T cells, treatment efficacy, overall survival, and T-cell subsets in pre- and post-treatment tumor biopsies. Treatment caused a significant (P < 0.0001) shift in T-cell subsets in blood, characterized by a proportional increase of CD8+ cells, and decrease of CD4+ cells. Concomitant treatment with cyclophosphamide and temozolomide resulted in less CD4+ decrease (P = 0.041) than cyclophosphamide only. Interestingly, we saw a correlation between T-cell changes in peripheral blood and the tumor site. This correlation was positive for CD8+ and inverse for CD4+ cells. These findings give insight to the interconnections between peripheral blood and tumor-infiltrating lymphocyte (TIL) populations regarding oncolytic virotherapy. In particular, our data suggest that induction of T-cell response is not sufficient for clinical response in the context of immunosuppressive tumors, and that peripheral blood T cells have a complicated and potentially misleading relationship with TILs. PMID:25655312

  20. Human invariant NKT cell subsets differentially promote differentiation, antibody production, and T cell stimulation by B cells in vitro.

    OpenAIRE

    O'Reilly, Vincent

    2013-01-01

    PUBLISHED Invariant NK T (iNKT) cells can provide help for B cell activation and Ab production. Because B cells are also capable of cytokine production, Ag presentation, and T cell activation, we hypothesized that iNKT cells will also influence these activities. Furthermore, subsets of iNKT cells based on CD4 and CD8 expression that have distinct functional activities may differentially affect B cell functions. We investigated the effects of coculturing expanded human CD4(+), CD8α(+), and ...

  1. Comparative genomics as a tool to reveal functional equivalences between human and mouse dendritic cell subsets.

    Science.gov (United States)

    Crozat, Karine; Guiton, Rachel; Guilliams, Martin; Henri, Sandrine; Baranek, Thomas; Schwartz-Cornil, Isabelle; Malissen, Bernard; Dalod, Marc

    2010-03-01

    During evolution, vertebrates have developed an adaptive immune system able to cope with a variety of pathogens. Dendritic cells (DCs) are central to this process. DCs integrate information derived from pathogens or endogenous danger signals and convey them to T lymphocytes. Most of the present knowledge on DCs was generated in mice or by using human DCs differentiated in vitro from monocytes. In both species, several DC subsets have been identified in vivo based on differences in their phenotypes, anatomical locations or functions. In mice, protective immunity against intracellular pathogens or tumors can be induced most efficiently by targeting antigens to the CD8 alpha(+) DCs, a subset of DCs which resides in lymphoid tissues and is especially efficient at cross-presenting exogenous antigens to CD8(+) T lymphocytes. In contrary, harnessing human DC subsets for medical purposes is currently hampered by insufficient knowledge about these cells. To overcome this cognitive gap, we are using comparative genomics as a tool for designing hypotheses and experiments to further characterize DC subset functions and their molecular control, including the investigation of the functional equivalences that might exist between human and mouse DC subsets. PMID:20193019

  2. Sterile Inflammation-Do innate lymphoid cell subsets play a role?

    Directory of Open Access Journals (Sweden)

    Shane E Russell

    2012-08-01

    Full Text Available The recent identification of several novel innate lymphoid cell subsets (iLCs has increased our understanding of the mechanisms which link the innate and adaptive immune systems. While the contribution of these subsets towards the pathogenesis of human disease remains largely to be determined, it seems likely that they will play a particularly important role in sterile inflammatory settings where the innate response is seen as a critical mediator of inflammation. Several recent studies have highlighted the role of endogenous damage associated molecular patterns such as IL-33, IL-1 and IL-1 in promoting lymphoid cell responses. This review discusses the influence of such endogenous danger signals on novel iLCs such as Lymphoid Tissue-inducer (LTi cells, innate type 2 helper cells and  T cells and explores how these responses may contribute to the development of an inflammatory response in a sterile setting.

  3. 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; Albrechtsen, A; Rieper, C de Lemos; Pedersen, B Klarlund; Larsen, L Kongskov; Thomsen, A Randrup; Pedersen, O; Hansen, M Bagge; Steensberg, A

    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...

  4. DBA-Lectin Reactivity Defines Mouse Uterine Natural Killer Cell Subsets with Biased Gene Expression 1

    Science.gov (United States)

    Chen, Zhilin; Zhang, Jianhong; Hatta, Kota; Lima, Patricia D. A.; Yadi, Hakim; Colucci, Francesco; Yamada, Aureo T.; Croy, B. Anne

    2012-01-01

    Endometrial decidualization, a process essential for blastocyst implantation in species with hemochorial placentation, is accompanied by an enormous but transient influx of Natural Killer (NK) cells. Mouse uterine (u)NK cell subsets have been defined by diameter and cytoplasmic granule number, reflecting stage of maturity and by histochemical reactivity with Periodic Acid Schiff’s (PAS) reagent, with or without co-reactivity with Dolichos biflorus agglutinin (DBA) lectin. We asked whether DBA− and DBA+ mouse uNK cells were equivalent using quantitative (q)RT-PCR analyses of flow separated, midpregnancy (gestation day (gd)10) cells and using immunohistochemistry. CD3E (CD3)-IL2RB (CD122)+DBA− cells were identified as the dominant Ifng transcript source. Skewed IFNG production by uNK cell subsets was confirmed by analysis of uNK cells from eYFP-tagged IFNG-reporter mice. In contrast, CD3E-IL2RB+DBA+ uNK cells expressed genes compatible with significantly greater potential for IL22 synthesis, angiogenesis and participation in regulation mediated by the renin-angiotensin system (RAS). CD3E-IL2RB+DBA+ cells were further divided into VEGFA+ and VEGFA− subsets. CD3E-IL2RB+DBA+ uNK cells but not CD3E-IL2RB+DBA− uNK cells arose from circulating, bone marrow-derived progenitor cells by gd6. These findings indicate the heterogeneous nature of mouse uNK cells and suggest that studies using only DBA + uNK cells will give biased data that does not fully represent the uNK cell population. PMID:22875907

  5. Expansion of an atypical NK cell subset in mouse models of SLE

    OpenAIRE

    Voynova, Elisaveta N.; Skinner, Jeffrey; Bolland, Silvia

    2015-01-01

    Chronic inflammatory conditions, such as in autoimmune disease, can disturb immune cell homeostasis and induce the expansion of normally rare cell populations. In our analysis of various murine models of lupus, we detect increased frequency of an uncommon subset identified as NK1.1+CD11c+CD122+MHC-II+. These cells share characteristics with the NK cell lineage and with cells previously described as IKDCs: (1) they depend on IL15 and express E4BP4; (2) they are cytotoxic and produce type I and...

  6. Delineation of breast cancer cell hierarchy identifies the subset responsible for dormancy

    OpenAIRE

    Patel, Shyam A; Ramkissoon, Shakti H.; Bryan, Margarette; Pliner, Lillian F.; Dontu, Gabriela; Patel, Prem S; Amiri, Sohrab; Pine, Sharon R.; Rameshwar#, Pranela

    2012-01-01

    The bone marrow (BM) is a major organ of breast cancer (BC) dormancy and a common source of BC resurgence. Gap junctional intercellular communication (GJIC) between BC cells (BCCs) and BM stroma facilitates dormancy. This study reports on a hierarchy of BCCs with the most immature subset (Oct4hi/CD44hi/med/CD24−/+) demonstrating chemoresistance, dormancy, and stem cell properties: self-renewal, serial passaging ability, cycling quiescence, long doubling time, asymmetric division, high metasta...

  7. DBA-Lectin Reactivity Defines Mouse Uterine Natural Killer Cell Subsets with Biased Gene Expression 1

    OpenAIRE

    Chen, Zhilin; Zhang, Jianhong; Hatta, Kota; Lima, Patricia D.A.; Yadi, Hakim; Colucci, Francesco; Yamada, Aureo T.; Croy, B. Anne

    2012-01-01

    Endometrial decidualization, a process essential for blastocyst implantation in species with hemochorial placentation, is accompanied by an enormous but transient influx of Natural Killer (NK) cells. Mouse uterine (u)NK cell subsets have been defined by diameter and cytoplasmic granule number, reflecting stage of maturity and by histochemical reactivity with Periodic Acid Schiff’s (PAS) reagent, with or without co-reactivity with Dolichos biflorus agglutinin (DBA) lectin. We asked whether DBA...

  8. Immunoelectron microscopic study of the distribution of T cell subsets in rheumatoid synovium

    OpenAIRE

    1983-01-01

    The perivascular mononuclear cell collections of the rheumatoid synovium were examined both at the light and electron microscopic level by an immunoperoxidase staining technique using monoclonal antibodies directed against T cell subsets. These accumulations were variable in composition and size, not only in specimens from different patients but in the same specimen. Some areas (lymphocyte-rich areas) contained mainly small lymphocytes in clusters and others (transitional areas) contained bla...

  9. Intrinsic features of the CD8α(-) dendritic cell subset in inducing functional T follicular helper cells.

    Science.gov (United States)

    Shin, Changsik; Han, Jae-A; Choi, Bongseo; Cho, Yoon-Kyoung; Do, Yoonkyung; Ryu, Seongho

    2016-04-01

    T follicular helper (Tfh) cells, a true B cell helper, have a critical role in enhancing humoral immune responses. However, the initial differentiation of Tfh cells by dendritic cells (DCs), the most potent antigen presenting cells, has not been clearly understood, particularly in the knowledge of the two major conventional dendritic cell subsets, CD8α(+) DCs or CD8α(-) DCs. Here we demonstrated that the localization of CD8α(-) DCs in the marginal zone (MZ) bridging channels is closely associated with the induction of CXCR5(+)CCR7(low) Tfh cells. We also showed that the major source of IL-6 for inducing Tfh cells is provided from the activated CD4(+) T cells induced by CD8α(-) DCs, and IL-6 directly secreted from the DC subsets seems minor. CD8α(-) DCs were superior in inducing functional Tfh cells over other antigen presenting cells including B cells. We here observed the unknown intrinsic features of the DC subsets, suggesting the potential of utilizing the CD8α(-) DC subset as therapeutic vaccine for the regulation of humoral immune responses. PMID:26850563

  10. Protection of human myeloid dendritic cell subsets against influenza A virus infection is differentially regulated upon TLR stimulation.

    Science.gov (United States)

    Baharom, Faezzah; Thomas, Saskia; Bieder, Andrea; Hellmér, Maria; Volz, Julia; Sandgren, Kerrie J; McInerney, Gerald M; Karlsson Hedestam, Gunilla B; Mellman, Ira; Smed-Sörensen, Anna

    2015-05-01

    The proinflammatory microenvironment in the respiratory airway induces maturation of both resident and infiltrating dendritic cells (DCs) upon influenza A virus (IAV) infection. This results in upregulation of antiviral pathways as well as modulation of endocytic processes, which affect the susceptibility of DCs to IAV infection. Therefore, it is highly relevant to understand how IAV interacts with and infects mature DCs. To investigate how different subsets of human myeloid DCs (MDCs) involved in tissue inflammation are affected by inflammatory stimulation during IAV infection, we stimulated primary blood MDCs and inflammatory monocyte-derived DCs (MDDCs) with TLR ligands, resulting in maturation. Interestingly, MDDCs but not MDCs were protected against IAV infection after LPS (TLR4) stimulation. In contrast, stimulation with TLR7/8 ligand protected MDCs but not MDDCs from IAV infection. The reduced susceptibility to IAV infection correlated with induction of type I IFNs. We found that differential expression of TLR4, TRIF, and MyD88 in the two MDC subsets regulated the ability of the cells to enter an antiviral state upon maturation. This difference was functionally confirmed using small interfering RNA and inhibitors. Our data show that different human MDC subsets may play distinct roles during IAV infection, as their capacity to induce type I IFNs is dependent on TLR-specific maturation, resulting in differential susceptibility to IAV infection. PMID:25801434

  11. Dimethyl fumarate treatment of relapsing-remitting multiple sclerosis influences B-cell subsets

    Science.gov (United States)

    Lundy, Steven K.; Wu, Qi; Wang, Qin; Dowling, Catherine A.; Taitano, Sophina H.; Mao, Guangmei

    2016-01-01

    Objective: To test the hypothesis that dimethyl fumarate (Tecfidera, BG-12) affects B-cell subsets in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: Peripheral blood B cells were compared for surface marker expression in patients with RRMS prior to initiation of treatment, after 4–6 months, and at more than 1 year of treatment with BG-12. Production of interleukin (IL)–10 by RRMS patient B cells was also analyzed. Results: Total numbers of peripheral blood B lymphocytes declined after 4–6 months of BG-12 treatment, due to losses in both the CD27+ memory B cells and CD27neg B-cell subsets. Some interpatient variability was observed. In contrast, circulating CD24highCD38high (T2-MZP) B cells increased in percentage in the majority of patients with RRMS after 4–6 months and were present in higher numbers in all of the patients after 12 months of treatment. The CD43+CD27+ B-1 B cells also increased at the later time point in most patients but were unchanged at 4–6 months compared to pretreatment levels. Purified B cells from 7 of the 9 patients with RRMS tested after 4–6 months of treatment were able to produce IL-10 following CD40 ligand stimulation, and the amount corresponded with the combined levels of T2-MZP and B-1 B cells in the sample. None of the patients with RRMS in this study have had a relapse while taking BG-12. Conclusions: These data suggest that BG-12 differentially affects B-cell subsets in patients with RRMS, resulting in increased numbers of circulating B lymphocytes with regulatory capacity. PMID:27006972

  12. Differences in the composition of the human antibody repertoire by B cell subsets in the blood

    Directory of Open Access Journals (Sweden)

    Eva Szymanska eMroczek

    2014-03-01

    Full Text Available The vast initial diversity of the antibody repertoire is generated centrally by means of a complex series of V (D J gene rearrangement events, variation in the site of gene segment joining, and TdT catalyzed N- region addition. Although the diversity is great, close inspection has revealed distinct and unique characteristics in the antibody repertoires expressed by different B cell developmental subsets. In order to illustrate our approach to repertoire analysis, we present an in-depth comparison of V (D J gene usage, hydrophobicity, length, DH reading frame, and amino acid usage between heavy chain repertoires expressed by immature, transitional, mature, memory IgD+, memory IgD-, and plasmacytes isolated from the blood of a single individual. Our results support the view that in both human and mouse the H chain repertoires expressed by individual, developmental B cell subsets appear to differ in sequence content. Sequencing of unsorted B cells from the blood is thus likely to yield an incomplete or compressed view of what is actually happening in the immune response of the individual. Our findings support the view that studies designed to correlate repertoire expression with diseases of immune function will likely require deep sequencing of B cells sorted by subset.

  13. Differential Frequency of CD8+ T Cell Subsets in Multiple Sclerosis Patients with Various Clinical Patterns.

    Science.gov (United States)

    Salehi, Zahra; Doosti, Rozita; Beheshti, Masoumeh; Janzamin, Ehsan; Sahraian, Mohammad Ali; Izad, Maryam

    2016-01-01

    Recent evidence points to a pathogenic role for CD8+ cytotoxic T (Tc) cells in Multiple sclerosis (MS). Based on cytokine profile, Tc cells can be divided into different subsets: IFN-γ (Tc1), IL-4 (Tc2), IL-10 (Tc10), IL-17 (Tc17), IL-21 (Tc21), IL-22 (Tc22) and TNF-α producing cells. In this study we evaluated the frequency of Tc cell subsets and the serum level of Tc17 differentiation cytokines in MS patients with different clinical patterns. We analyzed Tc cell subsets percentage in peripheral blood of relapsing-remitting (RRMS) (n = 28), secondary-progressive (SPMS) (n = 10) and primary-progressive (PPMS) (n = 4) MS patients in comparison to healthy controls (n = 15) using flow cytometry. Serum level of TGF-β, IL-6 and IL-23 were measured by ELISA. We showed elevated levels of Tc1 and Tc17 cells in SPMS and RRMS patients in relapse phase, respectively (P = 0.04). Interestingly, the percentage of TNF-α producing CD8+ T cells in relapse and remission phase of RRMS and SPMS patients were higher than controls (P = 0.01, P = 0.004, P = 0.01, respectively) and Tc21 increased in remission phase of RRMS compared to SPMS (P = 0.03). We also found higher frequency of CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase of RRMS compared to remission phase, SPMS patients and controls (P = 0.01, P = 0.004 and P = 0.02, respectively). TGF- β increased in sera of RRMS patients in remission phase (P = 0.03) and SPMS (P = 0.05) compared to healthy subjects. Increased level of Tc17 and CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase highlights the critical role of IL-17 in RRMS pathogenesis. PMID:27467597

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

    OpenAIRE

    Pike, R.; Thomas, N.; Workman, S.; Ambrose, L; D. Guzman; Sivakumaran, S.; Johnson, M.; Thorburn, D.; Harber, M; Chain, B; Stauss, H. 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 patien...

  15. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1.

    OpenAIRE

    Pillay, J.; Kamp, V.M.; van Hoffen, E; Visser, T.; Tak, T; Lammers, J. W.; Ulfman, L.H.; Leenen, L.P.H.; Pickkers, P; Koenderman, L

    2012-01-01

    Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models of cancer, infectious disease, bone marrow transplantation, and autoimmune disease. Here, we report the identification of a subset of mature human neutrophils (CD11cbright/CD62Ldim/CD11bbright/CD1...

  16. Subsets of human CD4+ regulatory T cells express the peripheral homing receptor CXCR3

    OpenAIRE

    Hoerning, André; Koss, Kerith; Datta, Dipak; Boneschansker, Leonard; Jones, Caroline N.; Wong, Ian Y.; Irimia, Daniel; Calzadilla, Katiana; Benitez, Fanny; Hoyer, Peter F.; Harmon, William E.; Briscoe, David M.

    2011-01-01

    Regulatory T cells (Tregs) migrate into peripheral sites of inflammation such as allografts undergoing rejection, where they serve to suppress the immune response. In this study, we find that ~30–40% of human CD25hi FOXP3+ CD4+ Tregs express the peripheral CXC chemokine receptor 3 (CXCR3) and that this subset has potent immunoregulatory properties. Consistently, we observed that proliferative responses as well as IFN-γ production were significantly higher using CXCR3-depleted versus undeplete...

  17. Differences in the composition of the human antibody repertoire by B cell subsets in the blood

    OpenAIRE

    Eva Szymanska eMroczek; Ippolito, Gregory C.; Tobias eRogosch; Kam Hon eHoi; Tracy A Hwangpo; Marsha G Brand; Yingxin eZhuang; Cun Ren eLiu; Schneider, David A; Michael eZemlin; Brown, Elizabeth E.; George eGeorgiou; Schroeder, Harry W.

    2014-01-01

    The vast initial diversity of the antibody repertoire is generated centrally by means of a complex series of V (D) J gene rearrangement events, variation in the site of gene segment joining, and TdT catalyzed N- region addition. Although the diversity is great, close inspection has revealed distinct and unique characteristics in the antibody repertoires expressed by different B cell developmental subsets. In order to illustrate our approach to repertoire analysis, we present an in-depth com...

  18. Differences in the Composition of the Human Antibody Repertoire by B Cell Subsets in the Blood

    OpenAIRE

    Mroczek, Eva Szymanska; Ippolito, Gregory C.; Rogosch, Tobias; Hoi, Kam Hon; Tracy A Hwangpo; Marsha G Brand; Zhuang, Yingxin; Liu, Cun Ren; Schneider, David A; Zemlin, Michael; Brown, Elizabeth E.; Georgiou, George; Schroeder, Harry W.

    2014-01-01

    The vast initial diversity of the antibody repertoire is generated centrally by means of a complex series of V(D)J gene rearrangement events, variation in the site of gene segment joining, and TdT catalyzed N-region addition. Although the diversity is great, close inspection has revealed distinct and unique characteristics in the antibody repertoires expressed by different B cell developmental subsets. In order to illustrate our approach to repertoire analysis, we present an in-depth comparis...

  19. Circulating activated T cell subsets in autoimmune thyroid diseases: differences between untreated and treated patients.

    Science.gov (United States)

    Ohashi, H; Okugawa, T; Itoh, M

    1991-11-01

    To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+ 2H4-, CD4+ 4B4+) and suppressor-inducer T (CD4+ 2H4+, CD4+ 4B4-) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+ T (Ia+ CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+ CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+ CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+ CD4+ cells and Ia+ CD8+ were also increased in patients with thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+ CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy. PMID:1684685

  20. 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

  1. Characterization and Quantification of Innate Lymphoid Cell Subsets in Human Lung.

    Directory of Open Access Journals (Sweden)

    Katrien C De Grove

    Full Text Available Innate lymphoid cells (ILC are a new family of innate immune cells that have emerged as important regulators of tissue homeostasis and inflammation. However, limited data are available concerning the relative abundance and characteristics of ILC in the human lung.The aim of this study was to characterize and enumerate the different ILC subsets in human lung by multi-color flow cytometry.Within the CD45+ Lin- CD127+ pulmonary ILC population, we identified group 1 (ILC1, group 2 (ILC2 and group 3 (ILC3 innate lymphoid cells using specific surface markers (i.e. IL12Rβ2, CRTH2 and CD117 respectively and key transcription factors (i.e. T-bet, GATA-3 and RORγT respectively. Based on the presence of NKp44, ILC3 were further subdivided in natural cytotoxicity receptor (NCR+ and NCR- ILC3. In addition, we demonstrated the production of signature cytokines IFN-γ, IL-5, IL-17A, IL-22 and GM-CSF in the pulmonary ILC population. Interestingly, we observed a tendency to a higher frequency of NCR- ILC3 in lungs of patients with chronic obstructive pulmonary disease (COPD compared with controls.We show that the three main ILC subsets are present in human lung. Importantly, the relative abundance of ILC subsets tended to change in COPD patients in comparison to control individuals.

  2. Identification of a CCR5-Expressing T Cell Subset That Is Resistant to R5-Tropic HIV Infection

    OpenAIRE

    Oswald-Richter, Kyra; Grill, Stacy M.; Leelawong, Mindy; Tseng, Michelle; Kalams, Spyros A.; Hulgan, Todd; Haas, David W.; Unutmaz, Derya

    2007-01-01

    Infection with HIV-1 perturbs homeostasis of human T cell subsets, leading to accelerated immunologic deterioration. While studying changes in CD4+ memory and naïve T cells during HIV-1 infection, we found that a subset of CD4+ effector memory T cells that are CCR7−CD45RO−CD45RA+ (referred to as TEMRA cells), was significantly increased in some HIV-infected individuals. This T cell subset displayed a differentiated phenotype and skewed Th1-type cytokine production. Despite expressing high lev...

  3. Methods for discovery and characterization of cell subsets in high dimensional mass cytometry data.

    Science.gov (United States)

    Diggins, Kirsten E; Ferrell, P Brent; Irish, Jonathan M

    2015-07-01

    The flood of high-dimensional data resulting from mass cytometry experiments that measure more than 40 features of individual cells has stimulated creation of new single cell computational biology tools. These tools draw on advances in the field of machine learning to capture multi-parametric relationships and reveal cells that are easily overlooked in traditional analysis. Here, we introduce a workflow for high dimensional mass cytometry data that emphasizes unsupervised approaches and visualizes data in both single cell and population level views. This workflow includes three central components that are common across mass cytometry analysis approaches: (1) distinguishing initial populations, (2) revealing cell subsets, and (3) characterizing subset features. In the implementation described here, viSNE, SPADE, and heatmaps were used sequentially to comprehensively characterize and compare healthy and malignant human tissue samples. The use of multiple methods helps provide a comprehensive view of results, and the largely unsupervised workflow facilitates automation and helps researchers avoid missing cell populations with unusual or unexpected phenotypes. Together, these methods develop a framework for future machine learning of cell identity. PMID:25979346

  4. IMBALANCE OF T-CELL SUBSETS IN IRANIAN ALLERGIC RHINITIS PATIENTS

    Directory of Open Access Journals (Sweden)

    Ahmad Massoud

    1995-07-01

    Full Text Available r'Iwenty-nine patients were studied to determine the number of CJ.j+ Tscell subsets in Iranian allergic rhinitis patients. The result was compared with that a/twenty-four nonatopic controls. The number of11 and CDS+T cell'and levels ofspeafic IgE and /g(;4 against weed pollens were also studied The number of lymphocyte subset, tltat is, CD-/+ C/29+and C1Jf CJ451t cells were determined hy doublelabeling immunofluorescence assay. The results showed that the number ofClJ-I+ CD.f.5It cells to; significantly higher in the patients (626 ± 251.-1cell'per one micro/iter ofperipheral blood than in control subjects (479A ± 78.2 cell per one microliter (P <(.05. However, there WlLf no statistical difference between the number oJCJ.f+ CD29+cells in the tH'O groups. There were no correlation between the number of CD.f CD.f5It cells ill tlte peripheral blood of allergic patients and levels of total and specific IgE, hut a direct correlation was found between tlte levels ofspecific IgE and specific IgG.j ill the sera oj allergic patients (r=O.55, P < 0.0(2.

  5. Multicolor flow cytometry analysis of blood cell subsets in patients given total body irradiation before bone marrow transplantation

    International Nuclear Information System (INIS)

    Bone marrow transplantation has often been closely linked with accidental or intentional therapeutical irradiation. In both situations, study of the radiosensitivity of human blood cell subsets is of interest. Using one-color flow cytometry analysis of B lymphocytes, T cell subsets, and natural killer cells, we previously reported that lymphocyte subsets exhibit equal radiosensitivity. Taking advantage of recent developments in the knowledge of leukocyte differentiation antigens and flow cytometry technology we undertook a study of blood cell subsets to search for rare populations exhibiting different radiosensitivity. Thirty patients, who were delivered a 12 Gy fractionated total body irradiation as part of their conditioning regimen before transplantation for malignant disorders, were studied using multicolor flow cytometry. T and B lymphocytes showed a sharp, radiation-induced decrease, with the B lymphocytes (cluster of differentiation (CD) 19+) being the most sensitive. When analyzed by multicolor flow cytometry all major lymphocyte subsets appeared equally sensitive to the in vivo irradiation. Therefore, all major lymphocyte subsets sharing the helper phenotype (naive or memory) and the cytotoxic phenotype appeared equally sensitive to in vivo whole body irradiation. In parallel, the CD34+ cell subset remained basically unchanged after whole body irradiation. Finally, the CD3-, 56+, 16+ natural killer cell subset was relatively radioresistant (91 and 74% of its initial value, after 2 and 4 Gy, respectively) as compared to other lymphocyte subsets. Our study provides evidence that T and B cell subsets seem to be highly radiosensitive in vivo. The CD34+ progenitor/stem cells and NK cells seem to be more radioresistant. This latter result might provide clues to the understanding of the pathophysiogeny of radiation-induced aplasia and of the engrafment/rejection process following bone marrow transplantation. 20 refs., 3 figs., 1 tab

  6. Multicolor flow cytometry analysis of blood cell subsets in patients given total body irradiation before bone marrow transplantation

    International Nuclear Information System (INIS)

    Purpose: Bone marrow transplantation has often been closely linked with accidental or intentional therapeutical irradiation. In both situations, study of the radiosensitivity of human blood cell subsets is of interest. Using one-color flow cytometry analysis of B lymphocytes, T cell subsets, and natural killer cells, we previously reported that lymphocyte subsets exhibit equal radiosensitivity. Taking advantage of recent developments in the knowledge of leukocyte differentiation antigens and flow cytometry technology we undertook a study of blood cell subsets to search for rare populations exhibiting different radiosensitivity. Methods and Materials: Thirty patients, who were delivered a 12 Gy fractionated total body irradiation as part of their conditioning regimen before transplantation for malignant disorders, were studied using multicolor flow cytometry. Results: T and B lymphocytes showed a sharp, radiation-induced decrease, with the B lymphocytes (cluster of differentiation (CD) 19+) being the most sensitive. When analyzed by multicolor flow cytometry, all major lymphocyte subsets appeared equally sensitive to the in vivo irradiation; that is, CD3+4+45RO+, CD3+4+45RA+, CD3+4+8-, CD3+4-8+. Therefore, all major lymphocyte subsets sharing the helper phenotype (naive or memory) and the cytotoxic phenotype appeared equally sensitive to in vivo whole body irradiation. In parallel, the CD34+ cell subset remained basically unchanged after whole body irradiation. Finally, the CD3-, 56+, 16+ natural killer cell subset was relatively radioresistant (91 and 74% of its initial value, after 2 and 4 Gy, respectively) as compared to other lymphocyte subsets. Conclusion: Our study provides evidence that T and B cell subsets seem to be highly radiosensitive in vivo. The CD34+ progenitor/stem cells and NK cells seem to be more radioresistant. This latter result might provide clues to the understanding of the pathophysiogeny of radiation-induced aplasia and of the engrafment

  7. CyTOF supports efficient detection of immune cell subsets from small samples.

    Science.gov (United States)

    Yao, Yi; Liu, Rebecca; Shin, Min Sun; Trentalange, Mark; Allore, Heather; Nassar, Ala; Kang, Insoo; Pober, Jordan S; Montgomery, Ruth R

    2014-12-15

    Analysis of immune cell states is paramount to our understanding of the pathogenesis of a broad range of human diseases. Immunologists rely on fluorescence cytometry for cellular analysis, and while detection of 8 markers is now well established, the overlap of fluorescent signals limits efficiency. Mass cytometry or CyTOF (Cytometry by Time-Of-Flight) is a new technology for multiparameter single cell analysis that overcomes many limitations of fluorescence-based flow cytometry and can routinely detect as many as 40 markers per sample. This technology provides tremendous detail for cellular analysis of multiple cell populations simultaneously and is a powerful technique for translational investigations. Here we present reproducible detection of immune cell subsets starting with as few as 10,000 cells. Our study provides methods to employ CyTOF for small samples, which is especially relevant for investigation of limited patient biopsies in translational and clinical research. PMID:25450003

  8. A subset of IL-17+ mesenchymal stem cells possesses anti-Candida albicans effect

    Institute of Scientific and Technical Information of China (English)

    Ruili Yang; Yi Liu; Peyman Kelk; Cunye Qu; Kentaro Akiyama; Chider Chen; Ikiru Atsuta

    2013-01-01

    Bone marrow mesenchymal stem cells (MSCs) comprise a heterogeneous population of postnatal progenitor cells with profound immunomodulatory properties,such as upregulation of Foxp3+ regulatory T cells (Tregs) and downregulation of Th17 cells.However,it is unknown whether different MSC subpopulations possess the same range of immunomodulatory function.Here,we show that a subset of single colony-derived MSCs producing IL-17 is different from bulk MSC population in that it cannot upregulate Tregs,downregulate Th17 cells,or ameliorate disease phenotypes in a colitis mouse model.Mechanistically,we reveal that IL-17,produced by these MSCs,activates the NFκB pathway to downregulate TGF-β production in MSCs,resulting in abolishment of MSC-based immunomodulation.Furthermore,we show that NFκB is able to directly bind to TGF-β promoter region to regulate TGF-β expression in MSCs.Moreover,these IL-17+ MSCs possess anti-Candida albicans growth effects in vitro and therapeutic effect in C.albicans-infected mice.In summary,this study shows that MSCs contain an IL-17+ subset capable of inhibiting C.albicans growth,but attenuating MSC-based immunosuppression via NFκB-mediated downregulation of TGF-β.

  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. 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...

  11. 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.

  12. Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets.

    Science.gov (United States)

    Ma, Cindy S; Wong, Natalie; Rao, Geetha; Nguyen, Akira; Avery, Danielle T; Payne, Kathryn; Torpy, James; O'Young, Patrick; Deenick, Elissa; Bustamante, Jacinta; Puel, Anne; Okada, Satoshi; Kobayashi, Masao; Martinez-Barricarte, Ruben; Elliott, Michael; Sebnem Kilic, Sara; El Baghdadi, Jamila; Minegishi, Yoshiyuki; Bousfiha, Aziz; Robertson, Nic; Hambleton, Sophie; Arkwright, Peter D; French, Martyn; Blincoe, Annaliesse K; Hsu, Peter; Campbell, Dianne E; Stormon, Michael O; Wong, Melanie; Adelstein, Stephen; Fulcher, David A; Cook, Matthew C; Stepensky, Polina; Boztug, Kaan; Beier, Rita; Ikincioğullari, Aydan; Ziegler, John B; Gray, Paul; Picard, Capucine; Boisson-Dupuis, Stéphanie; Phan, Tri Giang; Grimbacher, Bodo; Warnatz, Klaus; Holland, Steven M; Uzel, Gulbu; Casanova, Jean-Laurent; Tangye, Stuart G

    2016-07-25

    Naive CD4(+) T cells differentiate into specific effector subsets-Th1, Th2, Th17, and T follicular helper (Tfh)-that provide immunity against pathogen infection. The signaling pathways involved in generating these effector cells are partially known. However, the effects of mutations underlying human primary immunodeficiencies on these processes, and how they compromise specific immune responses, remain unresolved. By studying individuals with mutations in key signaling pathways, we identified nonredundant pathways regulating human CD4(+) T cell differentiation in vitro. IL12Rβ1/TYK2 and IFN-γR/STAT1 function in a feed-forward loop to induce Th1 cells, whereas IL-21/IL-21R/STAT3 signaling is required for Th17, Tfh, and IL-10-secreting cells. IL12Rβ1/TYK2 and NEMO are also required for Th17 induction. Strikingly, gain-of-function STAT1 mutations recapitulated the impact of dominant-negative STAT3 mutations on Tfh and Th17 cells, revealing a putative inhibitory effect of hypermorphic STAT1 over STAT3. These findings provide mechanistic insight into the requirements for human T cell effector function, and explain clinical manifestations of these immunodeficient conditions. Furthermore, they identify molecules that could be targeted to modulate CD4(+) T cell effector function in the settings of infection, vaccination, or immune dysregulation. PMID:27401342

  13. Natural killer cell (NK) subsets and NK-like T-cell populations in acute myeloid leukemias and myelodysplastic syndromes.

    Science.gov (United States)

    Aggarwal, N; Swerdlow, S H; TenEyck, S P; Boyiadzis, M; Felgar, R E

    2016-07-01

    The impact of the immune microenvironment on the behavior and therapeutic strategies for hematopoietic and lymphoid neoplasms is being increasingly recognized. Many functional studies of natural killer (NK) cell cytotoxic responses in myelodysplasia (MDS) and acute myeloid leukemia (AML) exist, but with limited data on these lymphocyte proportions and related T-cell subsets. The proportions of these cells and their prognostic implications were therefore investigated in 89 AML, 51 MDS, and 20 control marrows by flow cytometry. The median proportion of NK cells (relative to the total lymphocytes) was lower in AML versus controls (P = 0.01). Among AML, a lower proportion of NK cells predicted better survival, whereas a higher NK cell proportion was associated with the poor prognostic AML category (P = 0.002). NK cell proportions were similar in MDS, MDS subgroups, and control marrows. The relative proportion of the mature NK cell subset (CD56(dim) CD16/57(bright) ) was lower in AML and MDS versus controls (P = 0.006, P = 0.0002, respectively). The proportion of mature NK cells was not a prognostic indicator although fewer were seen in poor prognosis AML. In contrast, a lower proportion of mature NK cells correlated with worse survival in MDS (P = 0.027). A higher proportion of NK-like T-cells (of total lymphoid cells) was found in MDS compared to controls (P = 0.01). A lower proportion of NK-like T-cells predicted better survival in AML but not in MDS. Thus, the proportions of NK, NK-cell subsets, and NK-like T-cells vary in myeloid neoplasms, may potentially impact immunomodulatory therapies, and may impact outcome. © 2016 International Clinical Cytometry Society. PMID:26648320

  14. A novel mucosal RORγt+NKp46+ cell subset is a source of interleukin-22

    OpenAIRE

    Tomasello, Elena; Reynders, Ana; Vivier, Eric

    2009-01-01

    Lymphoid tissue-inducer cells are hematopoietic cells essential for the organogenesis of several lymphoid structures during both fetal and adult life, whereas natural killer cells are key effector lymphocytes of the innate immune system. A series of recent reports has identified RORγt+NKp46+ interleukin-22-producing cells in gut and tonsils that share features with both lymphoid tissue-inducer cells and natural killer cells and that may be involved in mucosal immunity and homeostasis.

  15. 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

  16. 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.

  17. Hes1 potentiates T cell lymphomagenesis by up-regulating a subset of notch target genes.

    Directory of Open Access Journals (Sweden)

    Darryll D Dudley

    Full Text Available BACKGROUND: Hairy/Enhancer of Split (Hes proteins are targets of the Notch signaling pathway and make up a class of basic helix-loop-helix (bHLH proteins that function to repress transcription. Data from Hes1 deficient mice suggested that Hes1, like Notch1, is necessary for the progression of early T cell progenitors. Constitutive activation of Notch is known to cause T cell leukemia or lymphoma but whether Hes1 has any oncogenic activity is not known. METHODOLOGY/PRINCIPAL FINDINGS: We generated mice carrying a Hes1 transgene under control of the proximal promote of the lck gene. Hes1 expression led to a reduction in numbers of total thymocytes, concomitant with the increased percentage and number of immature CD8+ (ISP T cells and sustained CD25 expression in CD4+CD8+ double positive (DP thymocytes. Hes1 transgenic mice develop thymic lymphomas at about 20 weeks of age with a low penetrance. However, expression of Hes1 significantly shortens the latency of T cell lymphoma developed in Id1 transgenic mice, where the function of bHLH E proteins is inhibited. Interestingly, Hes1 increased expression of a subset of Notch target genes in pre-malignant ISP and DP thymocytes, which include Notch1, Notch3 and c-myc, thus suggesting a possible mechanism for lymphomagenesis. CONCLUSIONS/SIGNIFICANCE: We have demonstrated for the first time that Hes1 potentiates T cell lymphomagenesis, by up-regulating a subset of Notch target genes and by causing an accumulation of ISP thymocytes particularly vulnerable to oncogenic transformation.

  18. Image analyzer-based assessment of tumor-infiltrating T cell subsets and their prognostic values in colorectal carcinomas.

    Directory of Open Access Journals (Sweden)

    Younghoon Kim

    Full Text Available To find useful tools to evaluate the prognosis in colorectal carcinoma (CRC patients, we investigated the prognostic values of tumor-infiltrating T lymphocyte subsets according to intratumoral subsites as well as clinical or molecular characteristics. Immunohistochemistry for CD8, CD45RO, and FOXP3 was performed, and densities of the T cell subsets in each tissue microarray core (cells/mm2 were measured by image analysis. In the training set (n = 218 of CRC, T cell subset densities in the invasion front were more strongly associated with patient outcome than those in the tumor center. In the validation set (n = 549, T cell subset densities in the invasion front were evaluated. Univariate analysis showed that all three T cell subset densities were significantly associated with longer progression free survival and overall survival time (p < 0.001. In multivariate analysis, a high CD45RO density correlated independently with longer progression free survival (p = 0.011 and overall survival time (p = 0.007 in CRC patients, regardless of tumor location or adjuvant chemotherapy status. Our results showed that CD45RO density in the invasion front was the only independent prognostic factor regarding CRC. However, CD8 and FOXP3 densities were also independent prognostic factors in certain clinical settings. Thus, image analysis of tissue microarray cores in the invasion front of CRC could be used as a valid method for evaluating the prognostic significance of T cell subset densities.

  19. A subset of AID-dependent B-1a cells initiates hypersensitivity and pneumococcal pneumonia resistance.

    Science.gov (United States)

    Askenase, Phillip W; Bryniarski, Krzysztof; Paliwal, Vipin; Redegeld, Frank; Groot Kormelink, Thomas; Kerfoot, Steven; Hutchinson, Andrew T; van Loveren, Henk; Campos, Regis; Itakura, Atsuko; Majewska-Szczepanik, Monika; Yamamoto, Natsuo; Nazimek, Katarzyn; Szczepanik, Marian; Ptak, Wold

    2015-12-01

    We propose that there is a special B-1a B cell subset ("sB-1a" cells) that mediates linked processes very early after immunization to initiate cutaneous contact sensitivity (CS), delayed-type hypersensitivity (DTH), and immune resistance to pneumococcal pneumonia. Our published data indicate that in CS and DTH, these initiating processes are required for elicitation of the delayed onset and late-occurring classical T cell-mediated responses. sB-1a cells resemble memory B2 cells, as they are stimulated within 1 h of immunization and depend on T helper cytokines-uniquely IL-4 from hepatic iNKT cells--for activation and rapid migration from the peritoneal cavity to the spleen to secrete IgM antibody (Ab) and Ab-derived free light chains (FLCs) by only 1 day after immunization. Unlike conventional B-1a (cB-1a) cell-produced IgM natural Ab, IgM Ab produced by sB-1a cells has high Ag affinity owing to immunoglobulin V-region mutations induced by activation-induced cytidine deaminase (AID). The dominant cB-1a cells are increased in immunized AID-deficient mice but do not mediate initiation, CS, or pneumonia resistance because natural Ab has relatively low Ag affinity because of unmutated germ-line V regions. In CS and DTH, sB-1a IgM Ag affinity is sufficiently high to mediate complement activation for generation of C5a that, together with vasoactive mediators such as TNF-α released by FLC-sensitized mast cells, activate local endothelium for extravascular recruitment of effector T cells. We conclude by discussing the possibility of functional sB-1 cells in humans. PMID:26662721

  20. Bulk enrichment of transplantable hemopoietic stem cell subsets from lipopolysaccharide-stimulated murine spleen.

    Science.gov (United States)

    Ploemacher, R E; Brons, R H; Leenen, P J

    1987-02-01

    Counterflow centrifugal elutriation (CCE) in combination with density flotation centrifugation and fluorescence-activated cell sorting on wheat-germ agglutinin-FITC(WGA)-binding cells within the light-scatter "blast window" were used consecutively to enrich pluripotent hemopoietic stem cells (HSC) in bulk from lipopolysaccharide-stimulated mouse spleen. The medium-to-strong WGA + ve fraction contained 3.10(6) cells isolated from 3-4 X 10(9) spleen cells, with an average of 126% day-12 CFU-S and 65% day-8 CFU-S as calculated on the basis of their seeding fraction, suggesting that virtually all cells represented in vivo macroscopic colony formers. In view of the large differences reported elsewhere between stem cell subsets differing in reconstitutive capacity and secondary stem cell generation ability, we also studied various isolated cell fractions with respect to spleen colony formation, radioprotective ability, and spleen- and marrow- repopulating ability. Day-8 and day-12 CFU-S copurified when isolated by CCE. Cells from a fraction with high affinity for WGA were most highly enriched for their radioprotective ability (RPA) and their ability to repopulate the cellularity of the spleen and femur of irradiated recipients. This fraction contained virtually pure day-12 CFU-S. However, the ability to generate secondary day-12 CFU-S and CFU-GM in irradiated organs was enriched most in the medium WGA + ve cell fraction. MRA and SRA, according to the latter criteria, could therefore be partly separated from day-12 CFU-S and RPA on the basis of affinity for WGA. The data strongly suggest that at least part of all day-12 CFU-S have a high potential to proliferate and differentiate into mature progeny, but a relatively low self-renewal ability, and may therefore not be representative of the genuine stem cell. PMID:2880746

  1. 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.

  2. Cell surface galectin-3 defines a subset of chemoresistant gastrointestinal tumor-initiating cancer cells with heightened stem cell characteristics.

    Science.gov (United States)

    Ilmer, Matthias; Mazurek, Nachman; Byrd, James C; Ramirez, Karen; Hafley, Margarete; Alt, Eckhard; Vykoukal, Jody; Bresalier, Robert S

    2016-01-01

    Recurrence of gastrointestinal adenocarcinomas after surgery and chemotherapy may be attributed, in part, to the presence of a small population of tumor-initiating cancer stem cells (CSC). The expression of galectin-3 (Gal3), a multifunctional oncolectin, has been associated with biological behaviors associated with CSC. We examined the ability of Gal3 to characterize the CSC phenotype, and to identify a clinically important gastrointestinal cancer CSC population. Human colorectal and pancreatic cancer cell lines were sorted to identify subpopulations expressing commonly used CSC markers, and Gal3-positive CSC subpopulations. The association of Gal3 with the stem cell properties and alterations of these phenotypes by manipulation of Gal3 expression was examined. Gastrointestinal cancer cell lines contain both Gal3-positive and Gal3-negative subpopulations. Gal3-positive CSCs are characterized by high ALDH activity, enhanced self-renewal ability in vitro (sphere formation) and tumor forming ability in vivo, and resistance to chemotherapeutic agents and death-receptor-mediated apoptosis compared to Gal3-negative CSCs. Silencing Gal3 modifies this behavior. Cell surface Gal3 expression identifies a subset of CSCs in gastrointestinal cancers with high levels of stem cell characteristics, including chemoresistance. This may provide a platform for developing treatment strategies that target CSC. PMID:27512958

  3. HIV-Infected Spleens Present Altered Follicular Helper T Cell (Tfh Subsets and Skewed B Cell Maturation.

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    Lucie Colineau

    Full Text Available Follicular helper T (Tfh cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab production. HIV-1 infection is associated with an altered B cell differentiation and Tfh isolated from lymph nodes of HIV-infected (HIV+ individuals provide inadequate B cell help in vitro. However, the mechanisms underlying this impairment of Tfh function are not fully defined. Using a unique collection of splenocytes, we compared the frequency, phenotype and transcriptome of Tfh subsets in spleens from HIV negative (HIV- and HIV+ subjects. We observed an increase of CXCR5+PD-1highCD57-Tfh and germinal center (GC CD57+ Tfh in HIV+ spleens. Both subsets showed a reduced mRNA expression of the transcription factor STAT-3, co-stimulatory, regulatory and signal transduction molecules as compared to HIV- spleens. Similarly, Foxp3 expressing follicular regulatory T (Tfr cells were increased, suggesting sustained GC reactions in chronically HIV+ spleens. As a consequence, GC B cell populations were expanded, however, complete maturation into memory B cells was reduced in HIV+ spleens where we evidenced a compromised production of B cell-activating cytokines such as IL-4 and IL-10. Collectively our data indicate that, although Tfh proliferation and GC reactions seem to be ongoing in HIV-infected spleens, Tfh "differentiation" and expression of costimulatory molecules is skewed with a profound effect on B cell maturation.

  4. 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.

  5. 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 (survival may have importance for the generation of anti-tumor immunity and post-transplantation immune sequelae such as GVHD. In addition, elucidation of the mechanism of death of APC and T cell subsets, as described in chapter 3, provides potential markers of cell death that can be correlated to good graft versus tumor (GVT) effects versus bad

  6. 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.

  7. 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. PMID:24637161

  8. 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. PMID:27227993

  9. 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.

  10. Relationship between regulatory T cells subsets and lipid profile in dyslipidemic patients: a longitudinal study during atorvastatin treatment

    OpenAIRE

    Guasti, Luigina; Maresca, Andrea Maria; Schembri, Laura; Rasini, Emanuela; Dentali, Francesco; Squizzato, Alessandro; Klersy, Catherine; Robustelli Test, Laura; Mongiardi, Christian; Campiotti, Leonardo; Ageno, Walter; Grandi, Anna Maria; Cosentino, Marco; Marino, Franca

    2016-01-01

    Background The CD4+ T-lymphocytes and their subtype CD4 + CD25highFoxP3+ regulatory T cells are receiving growing interest as major regulators of atherogenesis. We sought to investigate 1) whether the CD4 + cell subsets were expressed differently in dyslipidemic patients (Pts) and healthy subjects (HS) and 2) whether atorvastatin treatment could be associated in-vivo and in-vitro with cell changes in expression and functional response. Methods CD4+ subsets frequency (CD4 + CD25highFoxP3+, CD4...

  11. A novel subset of CD4+ TH2 memory/effector cells that produce inflammatory IL-17 cytokine and promote the exacerbation of chronic allergic asthma

    OpenAIRE

    Wang, Yui-Hsi; Voo, Kui Shin; Liu, Bo; Chen, Chun-Yu; Uygungil, Burcin; Spoede, William; Bernstein, Jonathan A; Huston, David P.; Liu, Yong-Jun

    2010-01-01

    The inflammatory cytokine interleukin (IL)-17 is involved in the pathogenesis of allergic diseases. However, the identity and functions of IL-17–producing T cells during the pathogenesis of allergic diseases remain unclear. Here, we report a novel subset of TH2 memory/effector cells that coexpress the transcription factors GATA3 and RORγt and coproduce TH17 and TH2 cytokines. Classical TH2 memory/effector cells had the potential to produce IL-17 after stimulation with proinflammatory cytokine...

  12. 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

    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...

  13. Siglec-1-positive plasmacytoid dendritic cells (pDCs) in human peripheral blood: A semi-mature and myeloid-like subset imbalanced during protective and autoimmune responses.

    Science.gov (United States)

    Wilhelm, Theresa R; Taddeo, Adriano; Winter, Oliver; Schulz, Axel Ronald; Mälzer, Julia-Nora; Domingo, Cristina; Biesen, Robert; Alexander, Tobias; Thiel, Andreas; Radbruch, Andreas; Hiepe, Falk; Gerl, Velia

    2016-02-01

    Plasmacytoid dendritic cells (pDCs) play a central role in the pathogenesis of systemic lupus erythematosus (SLE) as IFN-α producers and promoters of T-cell activation or tolerance. Here, we demonstrated by flow-cytometry and confocal microscopy that Siglec-1, a molecule involved in the regulation of adaptive immunoresponses, is expressed in a subset of semi-mature, myeloid-like pDCs in human blood. These pDCs express lower BDCA-2 and CD123 and higher HLA-DR and CD11c than Siglec-1-negative pDCs and do not produce IFN-α via TLR7/TLR9 engagement. In vitro, Siglec-1 expression was induced in Siglec-1-negative pDCs by influenza virus. Proportions of Siglec-1-positive/Siglec-1-negative pDCs were higher in SLE than in healthy controls and correlated with disease activity. Healthy donors immunized with yellow fever vaccine YFV-17D displayed different kinetics of the two pDC subsets during protective immune response. PDCs can be subdivided into two subsets according to Siglec-1 expression. These subsets may play specific roles in (auto)immune responses. PMID:26674280

  14. Candida albicans morphology and dendritic cell subsets determine T helper cell differentiation

    OpenAIRE

    Kashem, Sakeen W.; Igyarto, Botond Z.; Gerami-Nejad, Maryam; Kumamoto, Yosuke; Mohammed, Javed A.; Jarrett, Elizabeth; Drummond, Rebecca A.; Zurawski, Sandra M.; Zurawski, Gerard; Berman, Judith; Iwasaki, Akiko; Brown, Gordon D.; Kaplan, Daniel H.

    2015-01-01

    Candida albicans is a dimorphic fungus responsible for chronic mucocutaneous and systemic infections. Mucocutaneous immunity to C. albicans requires T helper-17 (Th17) cell differentiation that is thought to depend on recognition of filamentous C. albicans. Systemic immunity is considered T cell independent. Using a murine skin infection model, we compared T helper cell responses to yeast and filamentous C. albicans, We found that only yeast induced Th17 cell responses through a mechanism tha...

  15. A subset of herpes simplex virus replication genes induces DNA amplification within the host cell genome.

    Science.gov (United States)

    Heilbronn, R; zur Hausen, H

    1989-01-01

    Herpes simplex virus (HSV) induces DNA amplification of target genes within the host cell chromosome. To characterize the HSV genes that mediate the amplification effect, combinations of cloned DNA fragments covering the entire HSV genome were transiently transfected into simian virus 40 (SV40)-transformed hamster cells. This led to amplification of the integrated SV40 DNA sequences to a degree comparable to that observed after transfection of intact virion DNA. Transfection of combinations of subclones and of human cytomegalovirus immediate-early promoter-driven expression constructs for individual open reading frames led to the identification of six HSV genes which together were necessary and sufficient for the induction of DNA amplification: UL30 (DNA polymerase), UL29 (major DNA-binding protein), UL5, UL8, UL42, and UL52. All of these genes encode proteins necessary for HSV DNA replication. However, an additional gene coding for an HSV origin-binding protein (UL9) was required for origin-dependent HSV DNA replication but was dispensible for SV40 DNA amplification. Our results show that a subset of HSV replication genes is sufficient for the induction of DNA amplification. This opens the possibility that HSV expresses functions sufficient for DNA amplification but separate from those responsible for lytic viral growth. HSV infection may thereby induce DNA amplification within the host cell genome without killing the host by lytic viral growth. This may lead to persistence of a cell with a new genetic phenotype, which would have implications for the pathogenicity of the virus in vivo. Images PMID:2547992

  16. A subset of herpes simplex virus replication genes induces DNA amplification within the host cell genome

    Energy Technology Data Exchange (ETDEWEB)

    Heilbronn, R.; zur Hausen, H. (Deutsches Krebsforschungszentrum, Heidelberg (West Germany))

    1989-09-01

    Herpes simplex virus (HSV) induces DNA amplification of target genes within the host cell chromosome. To characterize the HSV genes that mediate the amplification effect, combinations of cloned DNA fragments covering the entire HSV genome were transiently transfected into simian virus 40 (SV40)-transformed hamster cells. This led to amplification of the integrated SV40 DNA sequences to a degree comparable to that observed after transfection of intact virion DNA. Transfection of combinations of subclones and of human cytomegalovirus immediate-early promoter-driven expression constructs for individual open reading frames led to the identification of sic HSV genes which together were necessary and sufficient for the induction of DNA amplification: UL30 (DNA polymerase), UL29 (major DNA-binding protein), UL5, UL8, UL42, and UL52. All of these genes encode proteins necessary for HSV DNA replication. However, an additional gene coding for an HSV origin-binding protein (UL9) was required for origin-dependent HSV DNA replication but was dispensable for SV40 DNA amplification. The results show that a subset of HSV replication genes is sufficient for the induction of DNA amplification. This opens the possibility that HSV expresses functions sufficient for DNA amplification but separate from those responsible for lytic viral growth. HSV infection may thereby induce DNA amplification within the host cell genome without killing the host by lytic viral growth. This may lead to persistence of a cell with a new genetic phenotype, which would have implications for the pathogenicity of the virus in vivo.

  17. 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...

  18. A human memory T-cell subset with stem cell-like properties

    OpenAIRE

    Gattinoni, Luca; Lugli, Enrico; Ji, Yun; Pos, Zoltan; Paulos, Chrystal M.; Quigley, Máire F.; Almeida, Jorge R.; Gostick, Emma; Yu, Zhiya; Carpenito, Carmine; Wang, Ena; Douek, Daniel C.; Price, David A.; June, Carl H.; Marincola, Francesco M.

    2011-01-01

    Immunological memory is thought to depend upon a stem cell-like, self-renewing population of lymphocytes capable of differentiating into effector cells in response to antigen re-exposure. Here we describe a long-lived human memory T-cell population that displays enhanced self-renewal and multipotent capacity to derive central memory, effector memory and effector T cells. These cells, specific for multiple viral and self-tumor antigens, were found within a CD45RO−, CCR7+, CD45RA+, CD62L+, CD27...

  19. A human memory T-cell subset with stem cell-like properties

    Science.gov (United States)

    Gattinoni, Luca; Lugli, Enrico; Ji, Yun; Pos, Zoltan; Paulos, Chrystal M.; Quigley, Máire F.; Almeida, Jorge R.; Gostick, Emma; Yu, Zhiya; Carpenito, Carmine; Wang, Ena; Douek, Daniel C.; Price, David A.; June, Carl H.; Marincola, Francesco M.; Roederer, Mario; Restifo, Nicholas P.

    2011-01-01

    Immunological memory is thought to depend upon a stem cell-like, self-renewing population of lymphocytes capable of differentiating into effector cells in response to antigen re-exposure. Here we describe a long-lived human memory T-cell population that displays enhanced self-renewal and multipotent capacity to derive central memory, effector memory and effector T cells. These cells, specific for multiple viral and self-tumor antigens, were found within a CD45RO−, CCR7+, CD45RA+, CD62L+, CD27+, CD28+ and IL-7Rα+ T-cell compartment characteristic of naïve T cells. However, they expressed increased levels of CD95, IL-2Rβ, CXCR3, and LFA-1, and exhibited numerous functional attributes distinctive of memory cells. Compared to known memory populations, these lymphocytes displayed increased proliferative capacity, more efficiently reconstituted immunodeficient hosts and mediated superior anti-tumor responses in a humanized mouse model. The identification of a human stem cell-like memory T-cell population is of direct relevance to the design of vaccines and T-cell therapies. PMID:21926977

  20. Mesenchymal stem cells differentially modulate effector CD8+ T cell subsets and exacerbate experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Glenn, Justin D; Smith, Matthew D; Calabresi, Peter A; Whartenby, Katharine A

    2014-10-01

    Mesenchymal stem cells (MSC) have emerged as a promising candidate for inflammatory suppression and disease amelioration, especially of neuro-inflammatory diseases such as multiple sclerosis (MS). Auto-reactive CD4+ and CD8+ T cells acquire pathogenic IFNγ-producing- (Type I) and IL-17A-producing- (Type 17) effector phenotypes in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Although MSC have been extensively demonstrated to suppress pathogenic effector CD4+ T cells and CD4+ T cell-mediated EAE, surprisingly few studies have addressed their modulation of effector CD8+ T cells represented in MS or their impact on CD8+ T cell-mediated EAE. We find that MSC differentially modulate CD8+ T cell development depending on effector T cell subtype. MSC drive activated low-IFNγ producers toward an enhanced high-IFNγ Tc1-like phenotype but strongly inhibit the production of IL-17A and Tc17 polarization in vitro. These observations are underscored by differential MSC modulation of T cell activation, proliferation, and signature transcription factor up-regulation. In addition, effector CD8+ T cells co-cultured with MSC exhibited increased production of IL-2, a molecule known to enhance IFNγ, yet suppress IL-17A, production. Based on these in vitro effects on CD8+ T cells, we next evaluated their impact on the severity of EAE. To better evaluate CD8+ T cells, we immunized mice with MOG37-50 , which is a CD8-targeted epitope. Our results revealed a worsening of disease, consistent with their in vitro stimulation of Tc1 cells. These findings highlight the emerging duality of MSC in immune modulation and provide implications for their future use in immune-related diseases. PMID:24911892

  1. 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. PMID:26606688

  2. Vorinostat Modulates the Imbalance of T Cell Subsets, Suppresses Macrophage Activity, and Ameliorates Experimental Autoimmune Uveoretinitis.

    Science.gov (United States)

    Fang, Sijie; Meng, Xiangda; Zhang, Zhuhong; Wang, Yang; Liu, Yuanyuan; You, Caiyun; Yan, Hua

    2016-03-01

    The purpose of the study was to investigate the anti-inflammatory efficiency of vorinostat, a histone deacetylase inhibitor, in experimental autoimmune uveitis (EAU). EAU was induced in female C57BL/6J mice immunized with interphotoreceptor retinoid-binding protein peptide. Vorinostat or the control treatment, phosphate-buffered saline, was administrated orally from 3 days before immunization until euthanasia at day 21 after immunization. The clinical and histopathological scores of mice were graded, and the integrity of the blood-retinal barrier was examined by Evans blue staining. T helper cell subsets were measured by flow cytometry, and the macrophage functions were evaluated with immunohistochemistry staining and immunofluorescence assays. The mRNA levels of tight junction proteins were measured by qRT-PCR. The expression levels of intraocular cytokines and transcription factors were examined by western blotting. Vorinostat relieved both clinical and histopathological manifestations of EAU in our mouse model, and the BRB integrity was maintained in vorinostat-treated mice, which had less vasculature leakage and higher mRNA and protein expressions of tight junction proteins than controls. Moreover, vorinostat repressed Th1 and Th17 cells and increased Th0 and Treg cells. Additionally, the INF-γ and IL-17A expression levels were significantly decreased, while the IL-10 level was increased by vorinostat treatment. Furthermore, due to the reduced TNF-α level, the macrophage activity was considerably inhibited in EAU mice. Finally, transcription factors, including STAT1, STAT3, and p65, were greatly suppressed by vorinostat treatment. Our data suggest that vorinostat might be a potential anti-inflammatory agent in the management of uveitis and other autoimmune inflammatory diseases. PMID:26798022

  3. The CD85j+ NK cell subset potently controls HIV-1 replication in autologous dendritic cells.

    Directory of Open Access Journals (Sweden)

    Daniel Scott-Algara

    Full Text Available Natural killer (NK cells and dendritic cells (DC are thought to play critical roles in the first phases of HIV infection. In this study, we examined changes in the NK cell repertoire and functions occurring in response to early interaction with HIV-infected DC, using an autologous in vitro NK/DC coculture system. We show that NK cell interaction with HIV-1-infected autologous monocyte-derived DC (MDDC modulates NK receptor expression. In particular, expression of the CD85j receptor on NK cells was strongly down-regulated upon coculture with HIV-1-infected MDDC. We demonstrate that CD85j(+ NK cells exert potent control of HIV-1 replication in single-round and productively HIV-1-infected MDDC, whereas CD85j(- NK cells induce a modest and transient decrease of HIV-1 replication. HIV-1 suppression in MDCC by CD85j(+ NK cells required cell-to-cell contact and did not appear mediated by cytotoxicity or by soluble factors. HIV-1 inhibition was abolished when NK-MDDC interaction through the CD85j receptor was blocked with a recombinant CD85j molecule, whereas inhibition was only slightly counteracted by blocking HLA class I molecules, which are known CD85j ligands. After masking HLA class I molecules with specific antibodies, a fraction of HIV-1 infected MDDC was still strongly stained by a recombinant CD85j protein. These results suggest that CD85j(+ NK cell inhibition of HIV-1 replication in MDDC is mainly mediated by CD85j interaction with an unknown ligand (distinct from HLA class I molecules preferentially expressed on HIV-1-infected MDDC.

  4. Dynamic regulation of effector IFN-γ-producing and IL-17-producing T cell subsets in the development of acute graft-versus-host disease.

    Science.gov (United States)

    Zhao, Kai; Ruan, Suhong; Yin, Lingling; Zhao, Dongmei; Chen, Chong; Pan, Bin; Zeng, Lingyu; Li, Zhenyu; Xu, Kailin

    2016-02-01

    Graft-versus-host disease (GVHD) as the predominant complication of allogeneic hematopoietic stem cell transplantation remains to be fully understood. It is known that the cytokines produced by allogeneic reactive effector CD4+ and CD8+ T cells are involved in GVHD. However, the regulation and coordination of IFN-γ-producing and IL-17-producing effector T cells remain unclear. The present study aimed to investigate the dynamic changes of alloantigen-specific effector CD4+ T and CD8+ T cell subsets by flow cytometry, which produce inflammatory cytokines involved in the multistep GVHD pathogenesis progress. The results demonstrated that IL-17-producing CD8+ T (Tc17) cells and IFN-γ+CD8+ T (Tc1) cells were detected in the early stage of GVHD. The differentiation of CD4+ T cells into Th1 cell (IFN-γ+CD4+ T) and Th17 (IL-17+CD4+ T) cells was later than that of the Tc1 and Tc17 cells. The effector CD4+ T and CD8+ T cell subsets either became exhausted or became memory cells, exhibiting a CD62L-CD44+ phenotype following marked expansion during GVHD. Furthermore, T cell-associated type I (IL-2 and IFN-γ) and type II (IL-4 and IL-10) classical cytokines exhibited coordinated dynamic regulation. It was concluded that the differentiation of cytokine-producing Tc1 and Tc17 cells may be the key step in the initiation of GVHD, whereas CD4+ effector Th1 and Th17 cells are considered to be pathophysiological factors leading to the continuous aggravation of GVHD. PMID:26647759

  5. Molecular signatures induced by interleukin-2 on peripheral blood mononuclear cells and T cell subsets

    Directory of Open Access Journals (Sweden)

    Stroncek David

    2006-06-01

    Full Text Available Experimentally, interleukin-2 (IL-2 exerts complex immunological functions promoting the proliferation, survival and activation of T cells on one hand and inducing immune regulatory mechanisms on the other. This complexity results from a cross talk among immune cells which sways the effects of IL-2 according to the experimental or clinical condition tested. Recombinant IL-2 (rIL-2 stimulation of peripheral blood mononuclear cells (PBMC from 47 donors of different genetic background induced generalized T cell activation and anti-apoptotic effects. Most effects were dependent upon interactions among immune cells. Specialized functions of CD4 and CD8 T cells were less dependent upon and often dampened by the presence of other PBMC populations. In particular, cytotoxic T cell effector function was variably affected with a component strictly dependent upon the direct stimulation of CD8 T cells in the absence of other PBMC. This observation may provide a roadmap for the interpretation of the discrepant biological activities of rIL-2 observed in distinct pathological conditions or treatment modalities.

  6. T cell antigen receptor expression by subsets of Ly-2-L3T4- (CD8-CD4-) thymocytes

    DEFF Research Database (Denmark)

    Wilson, A; Ewing, T; Owens, T; Scollay, R; Shortman, K

    1988-01-01

    major subset, Ly-1 low B2A2-M1/69+Thy-1+Pgp-1-, representing a phenotype similar to embryonic Ly-2-L3T4- thymocytes and the phenotype commonly isolated from adult thymocytes as Ly-1 "dull," lacked cells strongly positive for F23.1. In contrast, a series of subsets of adult CBA Ly-2-L3T4- thymocytes...... which were B2A2-M1/69- and Pgp-1+ all included strongly F23.1-positive cells. A minor subset, negative for most markers except Pgp-1 and presumed on the basis of this phenotype and some reconstitution studies to include the earliest intrathymic precursors, contained 28% F23.1-positive cells. However, no...... F.23.1-positive cells were detected in equivalent "prethymic" populations from bone marrow or from athymic mouse spleen. The subsets of Ly-2-L3T4- thymocytes which were Ly-1 high, B2A2-M1/69-, and Pgp-1+ all contained about 70% F23.1-positive cells, indicating a V beta 8 usage much higher than the...

  7. Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets

    OpenAIRE

    Ryan D Michalek; Gerriets, Valerie A.; Jacobs, Sarah R.; Macintyre, Andrew N.; MacIver, Nancie J.; Mason, Emily F.; Sullivan, Sarah A.; Nichols, Amanda G.; Rathmell, Jeffrey C.

    2011-01-01

    Stimulated CD4+ T lymphocytes can differentiate into effector T cell (Teff) or inducible regulatory T cell (Treg) subsets with specific immunological roles. We show that Teff and Treg require distinct metabolic programs to support these functions. Th1, Th2, and Th17 cells expressed high surface levels of the glucose transporter Glut1 and were highly glycolytic. Treg, in contrast, expressed low levels of Glut1 and had high lipid oxidation rates. Consistent with glycolysis and lipid oxidation p...

  8. 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.

  9. Different in vitro proliferation and cytokine-production inhibition of memory T-cell subsets after calcineurin and mammalian target of rapamycin inhibitors treatment.

    Science.gov (United States)

    Merino, David; San Segundo, David; Medina, Juan M; Rodrigo, Emilio; Asensio, Esther; Irure, Juan; Fernández-Fresnedo, Gema; Arias, Manuel A; López-Hoyos, Marcos

    2016-06-01

    Calcineurin inhibitors (CNI) and mammalian target of rapamycin inhibitors (mTORi) are the main immunosuppressants used for long-term maintenance therapy in transplant recipients to avoid acute rejection episodes. Both groups of immunosuppressants have wide effects and are focused against the T cells, although different impacts on specific T-cell subsets, such as regulatory T cells, have been demonstrated. A greater knowledge of the impact of immunosuppression on the cellular components involved in allograft rejection could facilitate decisions for individualized immunosuppression when an acute rejection event is suspected. Memory T cells have recently gained focus because they might induce a more potent response compared with naive cells. The impact of immunosuppressants on different memory T-cell subsets remains unclear. In the present study, we have studied the specific impact of CNI (tacrolimus) and mTORi (rapamycin and everolimus) over memory and naive CD4(+) T cells. To do so, we have analysed the proliferation, phenotypic changes and cytokine synthesis in vitro in the presence of these immunosuppressants. The present work shows a more potent effect of CNI on proliferation and cytokine production in naive and memory T cells. However, the mTORi permit the differentiation of naive T cells to the memory phenotype and allow the production of interleukin-2. Taken together, our data show evidence to support the combined use of CNI and mTORi in transplant immunosuppression. PMID:26931075

  10. Expression of CD11c Is Associated with Unconventional Activated T Cell Subsets with High Migratory Potential

    Science.gov (United States)

    Cantero, Jon; Tarrats, Antoni; Fernández, Marco Antonio; Sumoy, Lauro; Rodolosse, Annie; McSorley, Stephen J.

    2016-01-01

    CD11c is an α integrin classically employed to define myeloid dendritic cells. Although there is little information about CD11c expression on human T cells, mouse models have shown an association of CD11c expression with functionally relevant T cell subsets. In the context of genital tract infection, we have previously observed increased expression of CD11c in circulating T cells from mice and women. Microarray analyses of activated effector T cells expressing CD11c derived from naïve mice demonstrated enrichment for natural killer (NK) associated genes. Here we find that murine CD11c+ T cells analyzed by flow cytometry display markers associated with non-conventional T cell subsets, including γδ T cells and invariant natural killer T (iNKT) cells. However, in women, only γδ T cells and CD8+ T cells were enriched within the CD11c fraction of blood and cervical tissue. These CD11c+ cells were highly activated and had greater interferon (IFN)-γ secretory capacity than CD11c- T cells. Furthermore, circulating CD11c+ T cells were associated with the expression of multiple adhesion molecules in women, suggesting that these cells have high tissue homing potential. These data suggest that CD11c expression distinguishes a population of circulating T cells during bacterial infection with innate capacity and mucosal homing potential. PMID:27119555

  11. 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...

  12. Identification and characterization of human dendritic cell subsets in the steady state: a review of our current knowledge.

    Science.gov (United States)

    Patel, Vineet Indrajit; Metcalf, Jordan Patrick

    2016-04-01

    Dendritic cells (DC) are generally categorized as a group of rare antigen presenting cells that are to the crucial development of immune responses to pathogens and also of tolerance to self-antigens. Therefore, having the ability to identify DC in specific tissues and to test their functional abilities in the steady state are scientific gaps needing attention. Research on primary human DC is lacking due to their rarity and the difficulty of obtaining tissue samples. However, recent findings have shown that several different DC subsets exist, and that these subsets vary both by markers expressed and functions depending on their specific microenvironment. After discriminating from other cell types, DC can be split into myeloid and plasmacytoid fractions. While plasmacytoid DC express definite markers, CD123 and BDCA-2, myeloid DC encompass several different subsets with overlapping markers expressed. Such markers include the blood DC antigens BDCA-1 and BDCA-3, along with Langerin, CD1a and CD14. Marker specificity is further reduced when accounting for microenvironmental differences, as observed in the blood, primary lymphoid tissues, skin and lungs. The mixed leukocyte reaction (MLR) has been used to measure the strength of antigen presentation by specific DC subsets. Surface markers and MLR require standardization to enable consistent identification of and comparisons between DC subsets. To alleviate these issues, researchers have begun comparing DC subsets at the transcriptional level. This has allowed degrees of relatedness to be determined between DC in different microenvironments, and should be a continued area of focus in years to come. PMID:26956785

  13. 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

  14. A Subset of Mouse Colonic Goblet Cells Expresses the Bitter Taste Receptor Tas2r131

    OpenAIRE

    Simone Prandi; Marta Bromke; Sandra Hübner; Anja Voigt; Ulrich Boehm; Wolfgang Meyerhof; Maik Behrens

    2013-01-01

    The concept that gut nutrient sensing involves taste receptors has been fueled by recent reports associating the expression of taste receptors and taste-associated signaling molecules in the gut and in gut-derived cell lines with physiological responses induced by known taste stimuli. However, for bitter taste receptors (Tas2rs), direct evidence for their functional role in gut physiology is scarce and their cellular expression pattern remained unknown. We therefore investigated Tas2r express...

  15. Identification of autoreactive CD4+ and CD8+ T cell subsets resistant to PD-1 pathway blockade#

    OpenAIRE

    Pauken, Kristen E.; Nelson, Christine E; Martinov, Tijana; Spanier, Justin A.; Heffernan, James R; Sahli, Nathanael L; Quarnstrom, Clare F; Osum, Kevin C; Schenkel, Jason M.; Jenkins, Marc K.; Blazar, Bruce R; Vezys, Vaiva; Fife, Brian T.

    2015-01-01

    Programmed Death (PD)-1 promotes T cell tolerance. Despite therapeutically targeting this pathway for chronic infections and tumors, little is known about how different T cell subsets are affected during blockade. We examined PD-1/PD-L1 regulation of self-antigen-specific CD4 and CD8 T cells in autoimmune susceptible models. PD-L1 blockade increased insulin-specific effector CD4 T cells in Type 1 Diabetes. However, anergic islet-specific CD4 T cells were resistant to PD-L1 blockade. Additiona...

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

    OpenAIRE

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

    2011-01-01

    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

  17. Expression Patterns of Killer Cell Immunoglobulin-Like Receptors (KIR) of NK-Cell and T-Cell Subsets in Old World Monkeys

    OpenAIRE

    Hermes, Meike; Albrecht, Christina; Schrod, Annette; Brameier, Markus; Walter, Lutz

    2013-01-01

    The expression of killer cell immunoglobulin-like receptors (KIR) on lymphocytes of rhesus macaques and other Old World monkeys was unknown so far. We used our recently established monoclonal anti-rhesus macaque KIR antibodies in multicolour flow cytometry for phenotypic characterization of KIR protein expression on natural killer (NK) cells and T cell subsets of rhesus macaques, cynomolgus macaques, hamadryas baboons, and African green monkeys. Similar to human KIR, we found clonal expressio...

  18. Clinical significance of determination of serum leptin level, peripheral B cell number, T cell subset distribution type in patients with pregnancy induced hypertension

    International Nuclear Information System (INIS)

    Objective: To investigate the clinical significance of changes of serum leptin level, B cell number, T cell subsets in patients with pregnancy induced hypertension (PIH). Methods: Serum leptin levels (with RIA), peripheral B cell number, T cell subsets distribution type (with monoclonal anti-body technic) were determined in 32 patients with pregnaney induced hypertension (PIH) and 35 controls. Results: The serum leptin levels and B cell percentage were significantly higher in patients with PIH than those in controls (P<0.01), while the CD3, CD4 percentage and CD4/CD8 ratio were significantly lower (P<0.01). Conclusion: Determination of serum leptin levels and peripheral B cell number, T cell subsets distribution type might demonstrate immuno-disturbances in patients with pregnaney induced hypertension. (authors)

  19. The human CD77- B cell population represents a heterogeneous subset of cells comprising centroblasts, centrocytes, and plasmablasts, prompting phenotypical revision.

    Science.gov (United States)

    Högerkorp, Carl-Magnus; Borrebaeck, Carl A K

    2006-10-01

    The process of becoming an Ig-producing plasma cell takes the mature B cell through the germinal center, where Ig genes are diversified through somatic hypermutation and class switch recombination. To more clearly define functional characteristics of the germinal center dark zone centroblasts and the light zone centrocytes, we have performed expression analysis of the CD77(+) and CD77(-) populations, because CD77 has been accepted as a discriminator of centroblasts and centrocytes. Our results demonstrated that the CD77(+) and the CD77(-) populations lack functional associated expression programs discriminating the two populations. Both populations are shown to be actively cycling and to share common features associated with cell cycle regulation and DNA maintenance. They are also shown to have an equally active DNA repair program, as well as components involved in somatic hypermutation and class switch recombination. Moreover, the data also demonstrated that the CD77(-) population comprises cells with an already initiated plasma cell differentiation program. Together this demonstrates that CD77 does not discriminate centroblasts and centrocytes and that the CD77(-) population represents a heterogeneous subset of cells, comprising centroblasts, centrocytes, and plasmablast. PMID:16982868

  20. 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

  1. 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. PMID:27579340

  2. 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.

  3. Study on serum TNF-α level, B-cell count and T-cell subsets distribution in peripheral blood in patients with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Objective: To study the changes of serum TNF-α levels, B-cell count and T-cell subsets distribution in peripheral blood in patients with rheumatoid arthritis. Methods: Serum TNF-α levels (with RIA), B cell as well as T cell subsets distribution type (with monoclonal antibody technique) were examined in 37 patients with rheumatoid arthritis and 30 controls. Results Serum TNF-α levels and B lymphocytes count were significantly higher in the patients than those in controls (P3, CD4 and CD4/CD8 were obviously lower (P<0.01). Conclusion: Rheumatoid arthritis is an autoimmune disease with abnormal immunoregulation. (authors)

  4. Characterization of Liver CD8 T Cell Subsets that are Associated with Protection Against Pre-erythrocytic Plasmodium Parasites.

    Science.gov (United States)

    Zarling, Stasya; Krzych, Urszula

    2015-01-01

    Murine models of malaria, such as Plasmodium berghei (Pb) and Plasmodium yoelii (Py), have been used for decades to identify correlates of protection associated with immunization using radiation-attenuated sporozoites (RAS). To date, RAS is the only known immunization regimen to consistently deliver 100 % sterilizing immunity and is considered the "gold standard" of protection against malaria. The ability to isolate lymphocytes directly from the liver of immune mice has facilitated the identification of correlates of protection at the site of infection. Liver CD8 T cells have been identified as a key factor in mediating protection against challenge with infectious Plasmodium sporozoites. Liver CD3 + CD8 T cells can further be divided into subsets based on the expression of specific surface molecules and the increase of CD8 effector memory (TEM) cells (identified by the phenotype CD44(+)CD62L(-)) has been shown to mediate protection by releasing of IFN-γ while CD8 central memory (TCM) cells (CD44(+)CD62L(+)) are important for maintaining long-term protection.Identification of multiple CD8 T cell subsets present in the liver relies on the ability to detect multiple surface markers simultaneously. Polychromatic flow cytometry affords the user with the ability to distinguish multiple lymphocyte populations as well as subsets defined within each population. In this chapter we present a basic 9-color surface staining panel that can be used to identify CD8 TEM, CD8 TCM, short-lived effector cells (SLECs), and memory precursor cells (MPECs) as well as identify those cells which have recently undergone degranulation (surface expression of CD107a). This panel has been designed to allow for the addition of intracellular staining for IFN-γ on other available channels (such as PE) as is discussed in another chapter for analysis of functional CD8 T cell responses. PMID:26450377

  5. Differential requirements for the induction of interleukin 2 responsiveness in L3T4+ and Lyt-2+ T cell subsets

    OpenAIRE

    1985-01-01

    Minimal requirements for the induction of interleukin 2 (IL-2) responsiveness in purified subsets of murine T lymphocytes have been investigated. Whereas Lyt-2+ cells could be induced to IL-2-dependent growth by lectin, phorbol ester, or calcium ionophore, none of these stimuli was by itself sufficient for L3T4+ cells. The latter cells could, however, be induced to respond to IL-2 by combinations of lectin plus phorbol ester or ionophore plus phorbol ester (but not lectin plus ionophore). Und...

  6. Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion

    Science.gov (United States)

    Morita, Rimpei; Schmitt, Nathalie; Bentebibel, Salah-Eddine; Ranganathan, Rajaram; Bourdery, Laure; Zurawski, Gerard; Foucat, Emile; Dullaers, Melissa; Oh, SangKon; Sabzghabaei, Natalie; Lavecchio, Elizabeth M; Punaro, Marilynn; Pascual, Virginia; Banchereau, Jacques; Ueno, Hideki

    2011-01-01

    Although a fraction of human blood memory CD4+ T cells expresses chemokine (C-X-C motif) receptor 5 (CXCR5), their relationship to T follicular helper (Tfh) cells is not well-established. Here we show that human blood CXCR5+ CD4+ T cells share functional properties with Tfh cells, and appear to represent their circulating memory compartment. Blood CXCR5+ CD4+ T cells comprised three subsets; T helper 1 (Th1), Th2 and Th17 cells. Th2 and Th17 cells within CXCR5+, but not within CXCR5−, compartment efficiently induced naïve B cells to produce immunoglobulins via interleukin-21 (IL-21). In contrast, Th1 cells from both CXCR5+ and CXCR5− compartments lacked the capacity to help B cells. Patients with juvenile dermatomyositis, a systemic autoimmune disease, displayed a profound skewing of blood CXCR5+ Th subsets towards Th2 and Th17 cells. Importantly, the skewing of subsets correlated with disease activity and frequency of blood plasmablasts. Collectively, our study suggests that an altered balance of Tfh subsets contributes to human autoimmunity. PMID:21215658

  7. Distinct single cell signal transduction signatures in leukocyte subsets stimulated with khat extract, amphetamine-like cathinone, cathine or norephedrine

    OpenAIRE

    Bredholt, Therese; Ersvær, Elisabeth; Erikstein, Bjarte Skoe; Sulen, André; Reikvam, Håkon; Aarstad, Hans Jørgen; Johannessen, Anne Christine; Vintermyr, Olav Karsten; Bruserud, Øystein; Gjertsen, Bjørn Tore

    2013-01-01

    Background: Amphetamine and amphetamine derivatives are suggested to induce an immunosuppressive effect. However, knowledge of how amphetamines modulate intracellular signaling pathways in cells of the immune system is limited. We have studied phosphorylation of signal transduction proteins (Akt, CREB, ERK1/2, NF-κB, c-Cbl, STAT1/3/5/6) and stress sensors (p38 MAPK, p53) in human leukocyte subsets following in vitro treatment with the natural amphetamine cathinone, the cathinone d...

  8. γKlotho is a novel marker and cell survival factor in a subset of triple negative breast cancers

    Science.gov (United States)

    Trošt, Nuša; Peña-Llopis, Samuel; Koirala, Sajjan; Stojan, Jurij; Potts, Patrick Ryan; Tacer, Klementina Fon; Martinez, Elisabeth D.

    2016-01-01

    Over the last decade, breast cancer mortality has declined. However, triple negative breast cancer (TNBC) remains a challenging problem mostly due to early recurrence and lack of molecularly driven treatments. There is a critical need to identify subgroups of TNBC with common molecular features that can be therapeutically targeted. Here we show that in contrast to Klotho and βKlotho, the third member of the Klotho protein family, γKlotho, is overexpressed in more than 60% of TNBCs and correlates with poorer disease progression. Furthermore, we find that γKlotho is expressed in a subset of TNBC cell lines promoting cell growth. Importantly, we demonstrate that in these cells γKlotho is necessary for cell survival and that its depletion leads to constitutive ERK activation, cell cycle arrest and apoptosis. Interestingly, we observe increased oxidative stress in γKlotho-depleted cells suggesting that γKlotho enables cancer cells to cope with an oxidative environment and that cells become dependent on its expression to maintain this survival advantage. These findings indicate that γKlotho might be a potential marker for patients that would benefit from treatments that alter oxidative stress and constitutes a novel drug target for a subset of TN breast cancers. PMID:26556877

  9. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells.

    Science.gov (United States)

    Duhen, Thomas; Geiger, Rebekka; Jarrossay, David; Lanzavecchia, Antonio; Sallusto, Federica

    2009-08-01

    Interleukin 22 (IL-22) is a cytokine produced by the T(H)-17 lineage of helper T cells and NK-22 subset of natural killer cells that acts on epithelial cells and keratinocytes and has been linked to skin homeostasis and inflammation. Here we characterize a population of human skin-homing memory CD4(+) T cells that expressed the chemokine receptors CCR10, CCR6 and CCR4 and produced IL-22 but neither IL-17 nor interferon-gamma (IFN-gamma). Clones isolated from this population produced IL-22 only and had low or undetectable expression of the T(H)-17 and T helper type 1 (T(H)1) transcription factors RORgammat and T-bet. The differentiation of T cells producing only IL-22 was efficiently induced in naive T cells by plasmacytoid dendritic cells in an IL-6- and tumor necrosis factor-dependent way. Our findings delineate a previously unknown subset of human CD4(+) effector T cells dedicated to skin pathophysiology. PMID:19578369

  10. Chemokine receptor 7 (CCR7)-expression and IFNγ production define vaccine-specific canine T-cell subsets.

    Science.gov (United States)

    Hartley, Ashley N; Tarleton, Rick L

    2015-04-15

    Canines suffer from and serve as strong translational animals models for many immunological disorders and infectious diseases. Routine vaccination has been a mainstay of protecting dogs through the stimulation of robust antibody responses and expansion of memory T-cell populations. Commercially available reagents and described techniques are limited for identifying and characterizing canine T-cell subsets and evaluating T-cell-specific effector function. To define reagents for delineating naïve versus activated T-cells and identify antigen-specific T-cells, we tested anti-human and anti-bovine T-cell specific cell surface marker reagents for cross-reactivity with canine peripheral blood mononuclear cells (PBMCs. Both CD4(+) and CD8(+) T-cells from healthy canine donors showed reactivity to CCL19-Ig, a CCR7 ligand, and coexpression with CD62L. An in vitro stimulation with concanavalin A validated downregulation of CCR7 and CD62L expression on stimulated healthy control PBMCs, consistent with an activated T-cell phenotype. Anti-IFNγ antibodies identified antigen-specific IFNγ-producing CD4(+) and CD8(+) T-cells upon in vitro vaccine antigen PBMC stimulation. PBMC isolation within 24h of sample collection allowed for efficienT-cell recovery and accurate T-cell effector function characterization. These data provide a reagent and techniques platform via flow cytometry for identifying canine T-cell subsets and characterizing circulating antigen-specific canine T-cells for potential use in diagnostic and field settings. PMID:25758065

  11. 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...... 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...

  12. Transsynaptic transport of wheat germ agglutinin expressed in a subset of type II taste cells of transgenic mice

    Directory of Open Access Journals (Sweden)

    Mosinger Bedrich

    2008-10-01

    Full Text Available Abstract Background Anatomical tracing of neural circuits originating from specific subsets of taste receptor cells may shed light on interactions between taste cells within the taste bud and taste cell-to nerve interactions. It is unclear for example, if activation of type II cells leads to direct activation of the gustatory nerves, or whether the information is relayed through type III cells. To determine how WGA produced in T1r3-expressing taste cells is transported into gustatory neurons, transgenic mice expressing WGA-IRES-GFP driven by the T1r3 promoter were generated. Results Immunohistochemistry showed co-expression of WGA, GFP and endogenous T1r3 in the taste bud cells of transgenic mice: the only taste cells immunoreactive for WGA were the T1r3-expressing cells. The WGA antibody also stained intragemmal nerves. WGA, but not GFP immunoreactivity was found in the geniculate and petrosal ganglia of transgenic mice, indicating that WGA was transported across synapses. WGA immunoreactivity was also found in the trigeminal ganglion, suggesting that T1r3-expressing cells make synapses with trigeminal neurons. In the medulla, WGA was detected in the nucleus of the solitary tract but also in the nucleus ambiguus, the vestibular nucleus, the trigeminal nucleus and in the gigantocellular reticular nucleus. WGA was not detected in the parabrachial nucleus, or the gustatory cortex. Conclusion These results show the usefulness of genetically encoded WGA as a tracer for the first and second order neurons that innervate a subset of taste cells, but not for higher order neurons, and demonstrate that the main route of output from type II taste cells is the gustatory neuron, not the type III cells.

  13. 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. PMID:24664954

  14. Interleukin-22 binding protein (IL-22BP) is constitutively expressed by a subset of conventional dendritic cells and is strongly induced by retinoic acid.

    Science.gov (United States)

    Martin, J C J; Bériou, G; Heslan, M; Chauvin, C; Utriainen, L; Aumeunier, A; Scott, C L; Mowat, A; Cerovic, V; Houston, S A; Leboeuf, M; Hubert, F X; Hémont, C; Merad, M; Milling, S; Josien, R

    2014-01-01

    Interleukin-22 (IL-22) is mainly produced at barrier surfaces by T cells and innate lymphoid cells and is crucial to maintain epithelial integrity. However, dysregulated IL-22 action leads to deleterious inflammation and is involved in diseases such as psoriasis, intestinal inflammation, and cancer. IL-22 binding protein (IL-22BP) is a soluble inhibitory IL-22 receptor and may represent a crucial regulator of IL-22. We show both in rats and mice that, in the steady state, the main source of IL-22BP is constituted by a subset of conventional dendritic cells (DCs) in lymphoid and non-lymphoid tissues. In mouse intestine, IL-22BP was specifically expressed in lamina propria CD103(+)CD11b(+) DC. In humans, IL-22BP was expressed in immature monocyte-derived DC and strongly induced by retinoic acid but dramatically reduced upon maturation. Our data suggest that a subset of immature DCs may actively participate in the regulation of IL-22 activity in the gut by producing high levels of IL-22BP. PMID:23653115

  15. B7-H3 Promotes Pathogenesis of Autoimmune Disease and Inflammation by Regulating the Activity of Different T Cell Subsets.

    Directory of Open Access Journals (Sweden)

    Liqun Luo

    Full Text Available B7-H3 is a cell surface molecule in the immunoglobulin superfamily that is frequently upregulated in response to autoantigens and pathogens during host T cell immune responses. However, B7-H3's role in the differential regulation of T cell subsets remains largely unknown. Therefore, we constructed a new B7-H3 deficient mouse strain (B7-H3 KO and evaluated the functions of B7-H3 in the regulation of Th1, Th2, and Th17 subsets in experimental autoimmune encephalomyelitis (EAE, experimental asthma, and collagen-induced arthritis (CIA; these mouse models were used to predict human immune responses in multiple sclerosis, asthma, and rheumatoid arthritis, respectively. Here, we demonstrate that B7-H3 KO mice have significantly less inflammation, decreased pathogenesis, and limited disease progression in both EAE and CIA mouse models when compared with littermates; these results were accompanied by a decrease in IFN-γ and IL-17 production. In sharp contrast, B7-H3 KO mice developed severe ovalbumin (OVA-induced asthma with characteristic infiltrations of eosinophils in the lung, increased IL-5 and IL-13 in lavage fluid, and elevated IgE anti-OVA antibodies in the blood. Our results suggest B7-H3 has a costimulatory function on Th1/Th17 but a coinhibitory function on Th2 responses. Our studies reveal that B7-H3 could affect different T cell subsets which have important implications for regulating pathogenesis and disease progression in human autoimmune disease.

  16. 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

    2016-01-01

    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 bright)CD16-CD57-), and expressed the tissue-residency marker CD69. CXCR6+ NK produced fewer cytotoxic mediators and pro-inflammatory cytokines than the non-liver-specific CXCR6- fraction. Instead CXCR6+ NK could upregulate TRAIL, a key death ligand in hepatitis pathogenesis. CXCR6 demarcated liver NK into two transcriptionally distinct populations: T-bet(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. PMID:27210614

  17. A Subset of Protective γ9δ2 T Cells Is Activated by Novel Mycobacterial Glycolipid Components.

    Science.gov (United States)

    Xia, Mei; Hesser, Danny C; De, Prithwiraj; Sakala, Isaac G; Spencer, Charles T; Kirkwood, Jay S; Abate, Getahun; Chatterjee, Delphi; Dobos, Karen M; Hoft, Daniel F

    2016-09-01

    γ9δ2 T cells provide a natural bridge between innate and adaptive immunity, rapidly and potently respond to pathogen infection in mucosal tissues, and are prominently induced by both tuberculosis (TB) infection and bacillus Calmette Guérin (BCG) vaccination. Mycobacterium-expanded γ9δ2 T cells represent only a subset of the phosphoantigen {isopentenyl pyrophosphate [IPP] and (E)-4-hydroxy-3-methyl-but-2-enylpyrophosphate [HMBPP]}-responsive γ9δ2 T cells, expressing an oligoclonal set of T cell receptor (TCR) sequences which more efficiently recognize and inhibit intracellular Mycobacterium tuberculosis infection. Based on this premise, we have been searching for M. tuberculosis antigens specifically capable of inducing a unique subset of mycobacterium-protective γ9δ2 T cells. Our screening strategy includes the identification of M. tuberculosis fractions that expand γ9δ2 T cells with biological functions capable of inhibiting intracellular mycobacterial replication. Chemical treatments of M. tuberculosis whole-cell lysates (MtbWL) ruled out protein, nucleic acid, and nonpolar lipids as the M. tuberculosis antigens inducing protective γ9δ2 T cells. Mild acid hydrolysis, which transforms complex carbohydrate to monomeric residues, abrogated the specific activity of M. tuberculosis whole-cell lysates, suggesting that a polysaccharide was required for biological activity. Extraction of MtbWL with chloroform-methanol-water (10:10:3) resulted in a polar lipid fraction with highly enriched specific activity; this activity was further enriched by silica gel chromatography. A combination of mass spectrometry and nuclear magnetic resonance analysis of bioactive fractions indicated that 6-O-methylglucose-containing lipopolysaccharides (mGLP) are predominant components present in this active fraction. These results have important implications for the development of new immunotherapeutic approaches for prevention and treatment of TB. PMID:27297390

  18. Phenotypic Studies of Natural Killer Cell Subsets in Human Transporter Associated with Antigen Processing Deficiency

    OpenAIRE

    Zimmer, Jacques; Bausinger, Huguette; Andrès, Emmanuel; Donato, Lionel; Hanau, Daniel; Hentges, François; Moretta, Alessandro; de la Salle, Henri

    2007-01-01

    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 CD56bright 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 ...

  19. T cell subsets in HIV infected patients after successful combination antiretroviral therapy: impact on survival after 12 years.

    Directory of Open Access Journals (Sweden)

    Frederikke Falkencrone Rönsholt

    Full Text Available OBJECTIVES: Immune activation is decreased by combination antiretroviral therapy (cART in patients infected with human immunodeficiency virus (HIV, but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T-cell subsets after 18 months of cART and overall survival during 12 years of follow up. METHODS: A cohort of 101 HIV infected patients who had undetectable plasma HIV after starting cART was included in 1997-1998. T cell subsets were analyzed by flowcytometry after 18 months of cART. Relation to survival was calculated using Kaplan-Meier curves and multiple Cox regression. RESULTS: Seventeen patients died during the observation period. The leading causes of death were non-AIDS cancer and cardiovascular disease. Higher levels of CD8 memory T cells (CD8+,CD45RO+,CD45RA- showed a significant beneficiary effect on survival, HR of 0.95 (95% confidence interval 0.91-0.99, P = 0.016 when adjusted for age, nadir CD4 count, CD4 count, and AIDS and hepatitis C status. T cell activation was not associated with increased risk of death. CONCLUSIONS: Larger and longitudinal studies are needed to accurately establish prognostic factors, but overall results seem to suggest that prognostic information exists within the CD8 compartment.

  20. Changes in Natural Killer Cell Subsets in Pediatric Liver Transplant Recipients1

    OpenAIRE

    Pham, Betty; Piard-Ruster, Karine; Silva, Richard; Gallo, Amy; Esquivel, Carlos O.; Martinez, Olivia M.; Krams, Sheri M.

    2012-01-01

    Natural killer (NK) cells are important in the immune response against tumors and virally infected cells. A balance of inhibitory and activating receptors controls the effector functions of NK cells. We examined the fate of circulating NK cells and the expression of the NK cell activating receptors in pediatric liver transplant recipients. Blood specimens were collected from 38 pediatric liver transplant recipients before transplant, and at 1 week, 1, 3, 6, and 9 months, and 1 year post-trans...

  1. Characterization of a novel subset of CD8(+) T cells that expands in patients receiving interleukin-12.

    Science.gov (United States)

    Gollob, J A; Schnipper, C P; Orsini, E; Murphy, E; Daley, J F; Lazo, S B; Frank, D A; Neuberg, D; Ritz, J

    1998-08-01

    IL-12 has significant antitumor activity in mice that may be mediated by CD8(+) T cells. We show in this report that repeated subcutaneous injections of IL-12 in patients with cancer resulted in the selective expansion of a subset of peripheral blood CD8(+) T cells. This T cell subset expressed high levels of CD18 and upregulated IL-12 receptor expression after IL-12 treatment in vivo. In normal subjects, these CD3(+)CD8(+)CD18(bright) T cells expressed IL-12 and IL-2 receptors and adhesion/costimulatory molecules to a greater degree than other CD8(+) and CD4(+) T cells. They appeared morphologically as large granular lymphocytes, although they did not express NK cell markers such as CD56. In addition, CD8(+)CD18(bright) T cells were almost exclusively T cell receptor (TCR) alphabeta+, and exhibited a TCR Vbeta repertoire that was strikingly oligoclonal, whereas the Vbeta repertoire of CD18(dim) T cells was polyclonal. Although CD8+CD18(bright) T cells demonstrated little functional responsiveness to IL-12 or IL-2 alone in vitro, they responded to the combination of IL-12+IL-2 with strong IFN-gamma production and proliferation and enhanced non-MHC-restricted cytolytic activity. In contrast, CD18(dim) T cells were not activated by IL-12 or IL-2, alone or in combination. These findings demonstrate that CD8+CD18(bright) T cells are a unique population of peripheral blood lymphocytes with features of both memory and effector cells that are capable of TCR-independent activation through combined stimulation with IL-12+IL-2. As this activation results in IFN-gamma production and enhanced cytolytic activity, these T cells may play a role in innate as well as acquired immunity to tumors and infectious pathogens. Additional studies will be necessary to determine whether CD8+CD18(bright) T cells mediate the antitumor effect of IL-12 or IL-2 administered to cancer patients, and if so, whether maximal activation of these T cells with the combination of IL-12+IL-2 in vivo can

  2. A subset of dendritic cells induces CD4+ T cells to produce IFN-gamma by an IL-12-independent but CD70-dependent mechanism in vivo.

    Science.gov (United States)

    Soares, Helena; Waechter, HaeNa; Glaichenhaus, Nicholas; Mougneau, Evelyne; Yagita, Hideo; Mizenina, Olga; Dudziak, Diana; Nussenzweig, Michel C; Steinman, Ralph M

    2007-05-14

    Interferon (IFN)-gamma, a cytokine critical for resistance to infection and tumors, is produced by CD4(+) helper T lymphocytes after stimulation by cultured dendritic cells (DCs) that secrete a cofactor, interleukin (IL)-12. We have identified a major IL-12-independent pathway whereby DCs induce IFN-gamma-secreting T helper (Th)1 CD4(+) T cells in vivo. This pathway requires the membrane-associated tumor necrosis family member CD70 and was identified by targeting the LACK antigen from Leishmania major within an antibody to CD205 (DEC-205), an uptake receptor on a subset of DCs. Another major DC subset, targeted with 33D1 anti-DCIR2 antibody, also induced IFN-gamma in vivo but required IL-12, not CD70. Isolated CD205(+) DCs expressed cell surface CD70 when presenting antigen to T cell receptor transgenic T cells, and this distinction was independent of maturation stimuli. CD70 was also essential for CD205(+) DC function in vivo. Detection of the IL-12-independent IFN-gamma pathway was obscured with nontargeted LACK, which was presented by both DC subsets. This in situ analysis points to CD70 as a decision maker for Th1 differentiation by CD205(+) DCs, even in Th2-prone BALB/c animals and potentially in vaccine design. The results indicate that two DC subsets have innate propensities to differentially affect the Th1/Th2 balance in vivo and by distinct mechanisms. PMID:17438065

  3. Lineage relationship of CD8+ T cell subsets is revealed by progressive changes in the epigenetic landscape

    Science.gov (United States)

    Crompton, Joseph G.; Narayanan, Manikandan; Cuddapah, Suresh; Roychoudhuri, Rahul; Ji, Yun; Yang, Wenjing; Patel, Shashank J.; Sukumar, Madhusudhanan; Palmer, Douglas C.; Peng, Weiqun; Wang, Ena; Marincola, Francesco M.; Klebanoff, Christopher A.; Zhao, Keji; Tsang, John S.; Gattinoni, Luca; Restifo, Nicholas P.

    2016-01-01

    To better elucidate epigenetic mechanisms that correlate with the dynamic gene expression program observed upon T-cell differentiation, we investigated the genomic landscape of histone modifications in naive and memory CD8+ T cells. Using a ChIP-Seq approach coupled with global gene expression profiling, we generated genome-wide histone H3 lysine 4 (H3K4me3) and H3 lysine 27 (H3K27me3) trimethylation maps in naive, T memory stem cells, central memory cells, and effector memory cells in order to gain insight into how histone architecture is remodeled during T cell differentiation. We show that H3K4me3 histone modifications are associated with activation of genes, while H3K27me3 is negatively correlated with gene expression at canonical loci and enhancers associated with T-cell metabolism, effector function, and memory. Our results also reveal histone modifications and gene expression signatures that distinguish the recently identified T memory stem cells from other CD8+ T-cell subsets. Taken together, our results suggest that CD8+ lymphocytes undergo chromatin remodeling in a progressive fashion. These findings have major implications for our understanding of peripheral T-cell ontogeny and the formation of immunological memory. PMID:25914936

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

    OpenAIRE

    Aaron Topol; Shijia Zhu; Brigham J. Hartley; Jane English; Mads E. Hauberg; Ngoc Tran; Chelsea Ann Rittenhouse; Anthony Simone; Douglas M. Ruderfer; Jessica Johnson; Ben Readhead; Yoav Hadas; Peter A. Gochman; Ying-Chih Wang; Hardik Shah

    2016-01-01

    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 pre...

  5. T Cell Subsets in HIV Infected Patients after Successful Combination Antiretroviral Therapy: Impact on Survival after 12 Years

    OpenAIRE

    Rönsholt, Frederikke Falkencrone; Ostrowski, Sisse Rye; Katzenstein, Terese Lea; Ullum, Henrik; Gerstoft, Jan

    2012-01-01

    Objectives Immune activation is decreased by combination antiretroviral therapy (cART) in patients infected with human immunodeficiency virus (HIV), but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T-cell subsets after 18 months of cART and overall survival during 12 years of follow up. Methods A cohort of 101 HIV infected patients who had undetectable plasma HIV after starting cART was in...

  6. ESAM is a novel human hematopoietic stem cell marker associated with a subset of human leukemias.

    Science.gov (United States)

    Ishibashi, Tomohiko; Yokota, Takafumi; Tanaka, Hirokazu; Ichii, Michiko; Sudo, Takao; Satoh, Yusuke; Doi, Yukiko; Ueda, Tomoaki; Tanimura, Akira; Hamanaka, Yuri; Ezoe, Sachiko; Shibayama, Hirohiko; Oritani, Kenji; Kanakura, Yuzuru

    2016-04-01

    Reliable markers are essential to increase our understanding of the biological features of human hematopoietic stem cells and to facilitate the application of hematopoietic stem cells in the field of transplantation and regenerative medicine. We previously identified endothelial cell-selective adhesion molecule (ESAM) as a novel functional marker of hematopoietic stem cells in mice. Here, we found that ESAM can also be used to purify human hematopoietic stem cells from all the currently available sources (adult bone marrow, mobilized peripheral blood, and cord blood). Multipotent colony-forming units and long-term hematopoietic-reconstituting cells in immunodeficient mice were found exclusively in the ESAM(High) fraction of CD34(+)CD38(-) cells. The CD34(+)CD38(-) fraction of cord blood and collagenase-treated bone marrow contained cells exhibiting extremely high expression of ESAM; these cells are likely to be related to the endothelial lineage. Leukemia cell lines of erythroid and megakaryocyte origin, but not those of myeloid or lymphoid descent, were ESAM positive. However, high ESAM expression was observed in some primary acute myeloid leukemia cells. Furthermore, KG-1a myeloid leukemia cells switched from ESAM negative to ESAM positive with repeated leukemia reconstitution in vivo. Thus, ESAM is a useful marker for studying both human hematopoietic stem cells and leukemia cells. PMID:26774386

  7. Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

    Directory of Open Access Journals (Sweden)

    Margaret R Dunne

    Full Text Available Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets, natural killer cells, CD56(+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

  8. Transcriptome comparison of distinct osteolineage subsets in the hematopoietic stem cell niche using a triple fluorescent transgenic mouse model.

    Science.gov (United States)

    Yu, Vionnie W C; Lymperi, Stefania; Ferraro, Francesca; Scadden, David T

    2015-09-01

    The bone marrow niche is recognized as a central player in maintaining and regulating the behavior of hematopoietic stem and progenitor cells. Specific gain-of and loss-of function experiments perturbing a range of osteolineage cells or their secreted proteins had been shown to affect stem cell maintenance (Calvi et al, 2003 [1]; Stier et al., 2005 [2]; Zhang et al., 2003 [3]; Nilsson et al., 2005 [4]; Greenbaum et al., 2013 [5]) and engraftment (Adam et al., 2006, 2009 [6,7]). We used specific in vivo cell deletion approaches to dissect the niche cell-parenchymal cell dependency in a complex bone marrow microenvironment. Endogenous deletion of osteocalcin-expressing (Ocn(+)) cells led to a loss of T immune cells (Yu et al., 2015 [8]. Ocn(+) cells express the Notch ligand DLL4 to communicate with T-competent progenitors, and thereby ensuring T precursor production and expression of chemotactic molecules on their cell surface for subsequent thymic seeding. In contrast, depletion of osterix-expressing (Osx(+)) osteoprogenitors led to reduced B immune cells. These distinct hematopoietic phenotypes suggest specific pairing of mesenchymal niche cells and parenchymal hematopoietic cells in the bone marrow to create unique functional units to support hematopoiesis. Here, we present the global gene expression profiles of these osteolineage subtypes utilizing a triple fluorescent transgenic mouse model (OsxCre(+);Rosa-mCh(+);Ocn:Topaz(+)) that labels Osx(+) cells red, Ocn(+) cells green, and Osx(+) Ocn(+) cells yellow. This system allows isolation of distinct osteolineage subsets within the same animal by flow cytometry. Array data that have been described in our study [8] are also publically available from NCBI Gene Expression Omnibus (GEO) with the accession number GSE66042. Differences in gene expression may correlate with functional difference in supporting hematopoiesis. PMID:26484277

  9. Tc17 CD8 T Cells: Functional Plasticity and Subset Diversity1

    OpenAIRE

    Yen, Hung-Rong; Harris, Timothy J.; Wada, Satoshi; Grosso, Joseph F.; Getnet, Derese; Goldberg, Monica V.; Liang, Kai-Li; Bruno, Tullia C.; Pyle, Kristin J.; Chan, Siaw-Li; Anders, Robert A.; Trimble, Cornelia L.; Adler, Adam J.; Lin, Tzou-Yien; Pardoll, Drew M.

    2009-01-01

    IL-17-secreting CD8 T cells (Tc17) have been described in several settings, but little is known regarding their functional characteristics. While Tc1 cells produced IFN-γ and efficiently killed targets, Tc17 cells lacked lytic function in vitro. Interestingly, the small numbers of IFN-γ-positive or IL-17/IFN-γ-double-positive cells generated under Tc17 conditions also lacked lytic activity and expressed a similar pattern of cell surface proteins to IL-17-producing cells. As is the case for Th...

  10. Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells

    International Nuclear Information System (INIS)

    The authors have used polyclonal anti-synthetic peptide serum to study the role of retinoblastoma gene (RB) inactivation in a variety of human tumor cell lines. The analysis indicates that inactivation of the RB protein, p105-Rb, is universal in retinoblastoma cells, vindicating the predictions of the Knudson two-hit hypothesis. In addition, the analysis has shown that inactivations of the RB gene are nearly as frequent in a more common human tumor, small cell lung carcinoma. One-third of bladder carcinomas surveyed also carry altered or absent p105-Rb. Other human tumors by contrast demonstrate only infrequent inactivation of the RB gene. These results suggest that inactivation of the RB gene is a critical step in the pathogenesis of a subset of human tumors

  11. A distinct subset of self-renewing human memory CD8+ T cells survives cytotoxic chemotherapy

    OpenAIRE

    Turtle, Cameron J.; Swanson, Hillary M.; Fujii, Nobuharu; Estey, Elihu H.; Riddell, Stanley R.

    2009-01-01

    The mechanisms that maintain human T cell memory during normal and perturbed homeostasis are not fully understood. The repeated induction of profound lymphocytopenia in patients undergoing multiple cycles of cytotoxic chemotherapy infrequently results in severe infections with viruses controlled by memory T cells, suggesting that some memory T cells survive chemotherapy and restore immunity. Here we identify a distinct subpopulation of memory CD8+ T cells with the ability to rapidly efflux an...

  12. Direct and Differential Suppression of Myeloid-derived Suppressor Cell Subsets by Sunitinib is Compartmentally Constrained

    OpenAIRE

    Ko, Jennifer S.; Rayman, Patricia; Ireland, Joanna; Swaidani, Shadi; Li, Geqiang; Bunting, Kevin D.; Rini, Brian; Finke, James H.; Cohen, Peter A.

    2010-01-01

    The anti-angiogenic drug sunitinib is a receptor tyrosine-kinase inhibitor with significant, yet not curative, therapeutic impacts in metastatic renal cell carcinoma (mRCC). Sunitinib is also an immunomodulator, potently reversing myeloid-derived suppressor cell (MDSC) accumulation and T-cell inhibition in the blood even of non-responder RCC patients. We observed that sunitinib similarly prevented MDSC accumulation and restored normal T-cell function to spleens of tumor-bearing mice, independ...

  13. 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

    )-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...

  14. A Leukocyte Immune-Type Receptor Subset Is a Marker of Antiviral Cytotoxic Cells in Channel Catfish, Ictalurus punctatus.

    Science.gov (United States)

    Taylor, Erin B; Moulana, Mohadetheh; Stuge, Tor B; Quiniou, Sylvie M A; Bengten, Eva; Wilson, Melanie

    2016-03-15

    Channel catfish, Ictalurus punctatus, leukocyte immune type receptors (LITRs) represent a multigene family that encodes Ig superfamily proteins that mediate activating or inhibitory signaling. In this study, we demonstrate the use of mAb CC41 to monitor viral cytotoxic responses in catfish and determine that CC41 binds to a subset of LITRs on the surface of catfish clonal CTLs. Homozygous gynogenetic catfish were immunized with channel catfish virus (CCV)-infected MHC-matched clonal T cells (G14D-CCV), and PBL were collected at various times after immunization for flow cytometric analyses. The percentage of CC41(+) cells was significantly increased 5 d after primary immunization with G14D-CCV and at 3 d after a booster immunization as compared with control fish only injected with G14D. Moreover, CC41(+) cells magnetically isolated from the PBL specifically killed CCV-infected targets as measured by (51)Cr release assays and expressed messages for CD3γδ, perforin, and at least one of the CD4-like receptors as analyzed by RNA flow cytometry. When MLC effector cells derived from a G14D-CCV-immunized fish were preincubated with CC41 mAb, killing of G14D-CCV targets was reduced by ∼40%, suggesting that at least some LITRs have a role in target cell recognition and/or cytotoxicity. The availability of a LITR-specific mAb has allowed, to our knowledge for the first time, functional characterization of LITRs in an autologous system. In addition, the identification of an LITR subset as a cytotoxic cell marker will allow for more effective monitoring of catfish immune responses to pathogens. PMID:26856701

  15. Multisystem Langerhans' cell histiocytosis with pancreatic involvement.

    OpenAIRE

    Yu, R C; Attra, A; Quinn, C M; Krausz, T; Chu, A C

    1993-01-01

    Langerhans' cell histiocytosis, a rare disorder of unknown cause affecting both children and adults, can affect many different organs and present to a wide range of medical specialties. An infant with fatal multisystem Langerhans' cell histiocytosis in whom the pancreas and the intestine were extensively affected is reported. The direct pancreatic involvement by this disease has not previously been described.

  16. Study of T Cell subsets and IL-7 protein expression in HIV-1-infected patients after 7 years HAART

    Directory of Open Access Journals (Sweden)

    Shou C

    2011-11-01

    Full Text Available Abstract Objective To study the changes in T cell subsets and IL-7 in HIV-1-infected patients after seven years of highly active antiretroviral therapy (HAART. Methods Seventy-five individuals were included in this study (25 with effective HAART, 18 with ineffective HAART, 17 untreated HIV+ patients, and 15 volunteers in the HIV negative control group. The counts of CD4+, CD8+, CD8/CD38+, and CD8/HLADR+ T cells as well as the IL-7 protein expression was measured at 5 time points during a period of seven years in patients starting HAART (baseline and in the HIV negative control group. The expression of CD127 on CD3+ T cells was measured by flow cytometry at a single time point (after 7 years in patients with HAART and was compared with untreated HIV+ patients and the HIV negative control group. Results At baseline CD4+ T cell counts of HIV-1-infected patients were lower than that in the control group (p +, CD8/HLADR+ and CD8/CD38+ T cell counts were higher than those in the control group (p 0.01. After seven years of effective HAART, the CD4+ T cell counts had increased and the CD8+ T cell count had decreased, although not to the normal levels (p + and CD8/CD38+ T cell counts had gradually approached those of the control group (p > 0.05. In the ineffective HAART group, the CD8/CD38+ T cell count had not decreased significantly, and CD8/HLADR+ T cell count gradually decreased. Before treatment, IL-7 serum levels of patients were significantly higher than that in the control group (p p + CD8+ T cells in effective HAART patients was higher than in untreated HIV+ patients (p p + CD4+ T cells was not significantly different among the control group, untreated HIV+ patients and effective HAART group. Conclusion After seven years of effective HAART, the quantity and capacity of T cell subsets and IL-7 in HIV-1-infected patients had been partially restored, and the abnormal immune activation has significantly diminished.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Liver involvement in Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    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.)

  2. 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.)

  3. Differential requirement of CD28 costimulation for activation of murine CD8+ intestinal intraepithelial lymphocyte subsets and lymph node cells.

    Science.gov (United States)

    Gelfanov, V; Lai, Y G; Gelfanova, V; Dong, J Y; Su, J P; Liao, N S

    1995-07-01

    The CD8+CD4- (CD8+) murine small intestinal intraepithelial lymphocytes (IELs) contain two subpopulations, one expressing alpha alpha-CD8 homodimers and another alpha beta-CD8 heterodimers. In this study, plate-bound anti-TCR beta-chain (TCR-beta) mAb alone or combined with anti-CD28 mAb is used as a model system to study activation requirement of these two CD8+ IEL subsets. In contrast to CD8+ lymph node (LN) cells that require both TCR and CD28 triggering for activation, alpha beta-CD8+ IELs proliferate and produce IL-2 and IFN-gamma when stimulated with anti-TCR-beta mAb alone, and soluble CTLA-4 Ig has no effect on their responses. On the other hand, alpha alpha-CD8+ IELs neither make IL-2 or IFN-gamma nor proliferate even when both stimuli are provided. However, alpha alpha-CD8+ IELs are capable of proliferation in both CD8+ IEL subsets is lower than in CD8+ LN cells, which contributes to the weaker and delayed response of CD8+ IELs. PMID:7602124

  4. Identification of a subset of perpheral T-cell lymphoma, not otherwise specified, characterized by FOXP3-positive regulatory T-cell phenotype, HTLV-1 negativity and poor outcome

    DEFF Research Database (Denmark)

    Pedersen, Martin Bjerregård; Hamilton-Dutoit, Stephen Jacques; Bendix, Knud; Møller, Michael Boe; Raffeld, Mark; Pittaluga, S; Steiniche, Torben; Bergmann, A.; Vater, Inga; Siebert, Reiner; Chan, Wing C; D'Amore, Francesco Annibale

    2014-01-01

    Identification of a subset of perpheral T-cell lymphoma, not otherwise specified, characterized by FOXP3-positive regulatory T-cell phenotype, HTLV-1 negativity and poor outcome.......Identification of a subset of perpheral T-cell lymphoma, not otherwise specified, characterized by FOXP3-positive regulatory T-cell phenotype, HTLV-1 negativity and poor outcome....

  5. 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

    peripheral blood. Bronchial LPS induced a local inflammatory response with recruitment of CD4+ (P=0.014), CD8+ T cells (P=0.034), an increase in the proportion of CD4+CD25+CD127lowFoxp3+ regulatory T cells (Tregs) (P=0.045) and a tendency towards an increase in CD4+CD161+ cells (P=0.071) were observed....... CONCLUSIONS: A unique distribution of T cells with little day-to-day variation was found in human airways. An increase in Tregs after endobronchial LPS suggests a role for Tregs during early stages of pulmonary inflammation....

  6. 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.

  7. Molecular features of the complementarity determining region 3 motif of the T cell population and subsets in the blood of patients with chronic severe hepatitis B

    Directory of Open Access Journals (Sweden)

    Yang Jiezuan

    2011-12-01

    Full Text Available Abstract Background T cell receptor (TCR reflects the status and function of T cells. We previously developed a gene melting spectral pattern (GMSP assay, which rapidly detects clonal expansion of the T cell receptor β variable gene (TCRBV in patients with HBV by using quantitative real-time reverse transcription PCR (qRT-PCR with DNA melting curve analysis. However, the molecular profiles of TCRBV in peripheral blood mononuclear cells (PBMCs and CD8+, CD8- cell subsets from chronic severe hepatitis B (CSHB patients have not been well described. Methods Human PBMCs were separated and sorted into CD8+ and CD8- cell subsets using density gradient centrifugation and magnetic activated cell sorting (MACS. The molecular features of the TCRBV CDR3 motif were determined using GMSP analysis; the TCRBV families were cloned and sequenced when the GMSP profile showed a single-peak, indicative of a monoclonal population. Results The number of skewed TCRBV in the CD8+ cell subset was significantly higher than that of the CD8- cell subset as assessed by GMSP analysis. The TCRBV11 and BV7 were expressed more frequently than other members of TCRBV family in PBMCs and CD8+, CD8- subsets. Also the relatively conserved amino acid motifs were detected in the TCRBV22, BV18 and BV11 CDR3 in PBMCs among patients with CSHB. Conclusions The molecular features of the TCRBV CDR3 were markedly different among PBMCs and CD8+, CD8- cell subsets derived from CSHB patients. Analysis of the TCRBV expression in the CD8+ subset was more accurate in assessing the status and function of circulating T cells. The expression of TCRBV11, BV7 and the relatively conserved CDR3 amino acid motifs could also help to predict and treat patients with CSHB.

  8. Phenotyping of circulating CD8(+) T cell subsets in human cutaneous leishmaniasis

    Czech Academy of Sciences Publication Activity Database

    Khamesipour, A.; Rostami, M.N.; Tasbihi, M.; Mohammadi, A.M.; Shahrestani, T.; Sarrafnejad, A.; Sohrabi, Yahya; Eskandari, S.E.; Valian, H.K.

    2012-01-01

    Roč. 14, č. 9 (2012), s. 702-711. ISSN 1286-4579 Institutional research plan: CEZ:AV0Z50520514 Institutional support: RVO:68378050 Keywords : CD8(+) T cells * memory T cells * cutaneous leishmaniasis * IFN-gamma Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.920, year: 2012

  9. Regulator and effector functions of T-cell subsets in human Leishmania infections

    DEFF Research Database (Denmark)

    Kemp, M

    1997-01-01

    Because of an increasing number of patients suffering from Leishmania infections and because of the serious consequences of these infections more thorough knowledge of the host factors responsible for resistance and susceptibility to the diseases is needed. In murine models of Leishmania infections...... the cytokine production by CD4+ T cells has been identified as a major factor in determining the outcome of the infection. In these models Th1 cells producing IFN-gamma provide protection against the infection whereas Th2 cells producing IL-4 and IL-10 aggravate the disease. The fatal outcome of Leishmania...... infections in humans with defects in T-cell functions illustrates that these cells are fundamental in the defence against Leishmania in humans also. However, as for many other infectious diseases (meningococcal disease and other septicaemic conditions, pneumonia, viral hepatitis, schistosomiasis) the immune...

  10. In vitro dendritic cell generation and lymphocyte subsets in myeloma patients: influence of thalidomide and high-dose chemotherapy treatment.

    Science.gov (United States)

    Schütt, Philipp; Buttkereit, Ulrike; Brandhorst, Dieter; Lindemann, Monika; Schmiedl, Sven; Grosse-Wilde, Hans; Seeber, Siegfried; Nowrousian, Mohammad Resa; Opalka, Bertram; Moritz, Thomas

    2005-05-01

    While vaccination with antigen-pulsed dendritic cells (DCs) represents a promising therapeutic strategy in multiple myeloma (MM), clinical benefit, so far, has been limited to individual patients. To identify potential problems with this approach, we have analyzed the influence of treatment parameters, in particular high-dose chemotherapy (HD-CTX) and thalidomide, on in vitro DC generation and peripheral blood lymphocyte subsets in MM patients. From a total of 25 MM patients, including 14 patients on thalidomide treatment and 11 after HD-CTX, in vitro DC generation from peripheral blood monocytes under serum-free condition was investigated. In addition, peripheral blood lymphocyte subsets were assessed in 17 patients including 10 patients on thalidomide treatment and 9 patients after HD-CTX. Efficient in vitro generation of DCs (median 7.1x10(6)/100 ml peripheral blood; range 0.1-42.5x10(6)/100 ml peripheral blood) expressing DC-typical surface markers was observed in 23 MM patients (92%), although reduced expression of CD1a, CD40, CD83, and HLA-DR was observed in patients treated with thalidomide. With respect to lymphocyte subsets, MM patients showed significantly (pthalidomide (usually in combination with CTX). CD8+ lymphocytes were significantly increased in MM patients. Thus, despite the well-known deficiencies in their immune system, adequate numbers of DCs can be generated in most myeloma patients. In patients treated with thalidomide, however, it remains to be seen whether the reduced expression of co-stimulatory molecules has functional relevance. PMID:15750834

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

    International Nuclear Information System (INIS)

    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 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® 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: ► We tested 11 environmental compounds in a hESC metabolomics platform. ► Significant changes in secreted small molecule metabolites were observed. ► Perturbed mass features map to pathways critical for normal development and pregnancy. ► Arginine, proline, nicotinate, nicotinamide and glutathione pathways were affected.

  12. 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

  13. 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. PMID:25419849

  14. PD-L1 Expression Is Increased in a Subset of Basal Type Breast Cancer Cells

    OpenAIRE

    Soliman, Hatem; Khalil, Farah; Antonia, Scott

    2014-01-01

    Background Tumor cells express programmed death ligand 1 (PD-L1) and is a key immune evasion mechanism. PD-L1 expression in multiple breast cancer cell lines was evaluated to identify intrinsic differences that affect their potential for immune evasion. Methods PD-L1 expression was analyzed in six breast cancer cell lines: AU565&MCF7 (luminal), BT20&HCC1143 (basal A), MDA231&HCC38 (basal B). Surface and intracellular PD-L1 expression +/− interferon γ for 48 hours was measured by flow cytometr...

  15. 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

    , HLA-DR(+)CD38(+) T cells were determined. Ex vivo whole-blood cytokine production and Toll-like receptor (TLR)-4 expression on Tregs were measured. Absolute number of CD3(+)CD4(+) (P = .026), CD3(+)CD8(+) (P = .046), Tregs (P = .023), and CD4(+)CD161(+) cells (P = .042) decreased after endotoxin...... administration. The frequency of anti-inflammatory Tregs increased (P = .033), whereas the frequency of proinflammatory CD4(+)CD161(+) cells decreased (P = .034). Endotoxemia was associated with impaired whole-blood production of tumor necrosis factor-α, interleukin-10, IL-6, IL-17, IL-2, and interferon-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...

  16. 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...

  17. 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

  18. 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)

    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

  19. Transforming growth factor-β suppresses metastasis in a subset of human colon carcinoma cells

    International Nuclear Information System (INIS)

    TGFβ signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally associated with progression of malignancy. However, we present evidence here for an anti-metastatic role of TGFβ signaling. To test the importance of TGFβ signaling to cell survival and metastasis we compared human colon carcinoma cell lines that are either non-tumorigenic with TGFβ response (FET), or tumorigenic with TGFβ response (FETα) or tumorigenic with abrogated TGFβ response via introduction of dominant negative TGFβRII (FETα/DN) and their ability to metastasize. Metastatic competency was assessed by orthotopic transplantation. Metastatic colony formation was assessed histologically and by imaging. Abrogation of TGFβ signaling through introduction of a dominant negative TGFβ receptor II (TGFβRII) in non-metastatic FETα human colon cancer cells permits metastasis to distal organs, but importantly does not reduce invasive behavior at the primary site. Loss of TGFβ signaling in FETα-DN cells generated enhanced cell survival capabilities in response to cellular stress in vitro. We show that enhanced cellular survival is associated with increased AKT phosphorylation and cytoplasmic expression of inhibitor of apoptosis (IAP) family members (survivin and XIAP) that elicit a cytoprotective effect through inhibition of caspases in response to stress. To confirm that TGFβ signaling is a metastasis suppressor, we rescued TGFβ signaling in CBS metastatic colon cancer cells that had lost TGFβ receptor expression due to epigenetic repression. Restoration of TGFβ signaling resulted in the inhibition of metastatic colony formation in distal organs by these cells. These results indicate that TGFβ signaling has an important role in the suppression of metastatic potential in tumors that have already progressed to the stage of an invasive carcinoma. The observations presented here indicate a metastasis suppressor role for TGF

  20. CyTOF supports efficient detection of immune cell subsets from small samples

    OpenAIRE

    YAO, YI; Liu, Rebecca; Shin, Min Sun; Trentalange, Mark; Allore, Heather; Nassar, Ala; Kang, Insoo; Pober, Jordan; Montgomery, Ruth R.

    2014-01-01

    Analysis of immune cell states is paramount to our understanding of the pathogenesis of a broad range of human diseases. Immunologists rely on fluorescence cytometry for cellular analysis, and while detection of 8 markers is now well established, the overlap of fluorescent signals limits efficiency. Mass cytometry or CyTOF (Cytometry by Time-Of-Flight) is a new technology for multiparameter single cell analysis that overcomes many limitations of fluorescence-based flow cytometry and can routi...

  1. Hydrodynamic guiding for addressing subsets of immobilized cells and molecules in microfluidic systems

    Directory of Open Access Journals (Sweden)

    Beyer Michael

    2003-07-01

    Full Text Available Abstract Background The interest in microfluidics and surface patterning is increasing as the use of these technologies in diverse biomedical applications is substantiated. Controlled molecular and cellular surface patterning is a costly and time-consuming process. Methods for keeping multiple separate experimental conditions on a patterned area are, therefore, needed to amplify the amount of biological information that can be retrieved from a patterned surface area. We describe, in three examples of biomedical applications, how this can be achieved in an open microfluidic system, by hydrodynamically guiding sample fluid over biological molecules and living cells immobilized on a surface. Results A microfluidic format of a standard assay for cell-membrane integrity showed a fast and dose-dependent toxicity of saponin on mammalian cells. A model of the interactions of human mononuclear leukocytes and endothelial cells was established. By contrast to static adhesion assays, cell-cell adhesion in this dynamic model depended on cytokine-mediated activation of both endothelial and blood cells. The microfluidic system allowed the use of unprocessed blood as sample material, and a specific and fast immunoassay for measuring the concentration of C-reactive protein in whole blood was demonstrated. Conclusion The use of hydrodynamic guiding made multiple and dynamic experimental conditions on a small surface area possible. The ability to change the direction of flow and produce two-dimensional grids can increase the number of reactions per surface area even further. The described microfluidic system is widely applicable, and can take advantage of surfaces produced by current and future techniques for patterning in the micro- and nanometer scale.

  2. Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells

    Science.gov (United States)

    Gallina, Giovanna; Dolcetti, Luigi; Serafini, Paolo; Santo, Carmela De; Marigo, Ilaria; Colombo, Mario P.; Basso, Giuseppe; Brombacher, Frank; Borrello, Ivan; Zanovello, Paola; Bicciato, Silvio; Bronte, Vincenzo

    2006-01-01

    Active suppression of tumor-specific T lymphocytes can limit the efficacy of immune surveillance and immunotherapy. While tumor-recruited CD11b+ myeloid cells are known mediators of tumor-associated immune dysfunction, the true nature of these suppressive cells and the fine biochemical pathways governing their immunosuppressive activity remain elusive. Here we describe a population of circulating CD11b+IL-4 receptor α+ (CD11b+IL-4Rα+), inflammatory-type monocytes that is elicited by growing tumors and activated by IFN-γ released from T lymphocytes. CD11b+IL-4Rα+ cells produced IL-13 and IFN-γ and integrated the downstream signals of these cytokines to trigger the molecular pathways suppressing antigen-activated CD8+ T lymphocytes. Analogous immunosuppressive circuits were active in CD11b+ cells present within the tumor microenvironment. These suppressor cells challenge the current idea that tumor-conditioned immunosuppressive monocytes/macrophages are alternatively activated. Moreover, our data show how the inflammatory response elicited by tumors had detrimental effects on the adaptive immune system and suggest novel approaches for the treatment of tumor-induced immune dysfunctions. PMID:17016559

  3. The expression of CD8α discriminates distinct T cell subsets in teleost fish.

    Science.gov (United States)

    Takizawa, Fumio; Dijkstra, Johannes Martinus; Kotterba, Paul; Korytář, Tomáš; Kock, Holger; Köllner, Bernd; Jaureguiberry, Beltran; Nakanishi, Teruyuki; Fischer, Uwe

    2011-07-01

    CD8, belonging to the TCR complex, is the main marker molecule of CTLs. Although CD8 genes have been detected in many fish species, the analysis of teleost CD8+ cells has been limited because of the lack of antibodies. Using newly established mAbs against rainbow trout CD8α, we found high ratios of CD8α+ cells in trout thymus, gill and intestine, but relatively low abundance in pronephros, spleen and blood. Accordingly, tissue sections revealed many CD8α+ cells in thymus, numerous intra- and subepithelial CD8α+ cells in intestine and gill and few scattered CD8α+ cells in spleen and pronephros. In secondary lymphoid tissues, CD8α+ lymphocytes, which did not react with anti-thrombocyte or anti-IgM mAbs, expressed CD8α, CD8β and TCRα, while Ig and CD4 transcripts were found in CD8α⁻ lymphocytes. In contrast, considerable CD4 expression in CD8α+ thymocytes suggests the presence of double-positive early T cells. Highly expressed TCRγ, LAG3 and CTLA4 in CD8α+ lymphocytes imply that they constitute a heterogeneous population different from found in non-mucosal tissues. PHA stimulation resulted in an up-regulation of CTL effector genes (perforin, granulysin and IFN-γ) in CD8α+ pronephrocytes, while both Th1 (IFN-γ) and Th2 (IL-4/13A) cytokines were up-regulated in CD8α⁻ pronephrocytes. Although the basic characteristics of CD8α+ lymphocytes seem similar in teleost and mammals, features such as the low proportion of teleost CD8α+ lymphocytes in blood and their high abundance in respiratory tissue reveal a unique dynamics and distribution. PMID:21352850

  4. Yupingfeng Pulvis Regulates the Balance of T Cell Subsets in Asthma Mice

    Directory of Open Access Journals (Sweden)

    Zhigang Wang

    2016-01-01

    Full Text Available Background. Yupingfeng Pulvis (HFBP had played an active role in many diseases, especially respiratory tract infections. Exploring the possible prevention mechanism of HFBP may provide new ideas in clinical applications for this well-known herbal formula. Purpose. To study the possible mechanisms of therapy effect of HFBP on asthma mice via regulating the balance of Tregs and Th17 cells. Method. The female BALB/c mice were divided into five groups: control group, model group, prednisone (5.5 mg/kg group, and 22 g/kg HFBP and 44 g/kg HFBP groups. Ovalbumin was used to make the asthma model of mice; the drug was ig administered daily after atomization for consecutive 15 d. The mice were killed after the last administration. The paraffin-embedded tissue sections of the lungs were stained by H&E. Tregs and Th17 cells in bronchoalveolar lavage fluid were detected by flow cytometry. IL-4, TGF-β, and TNF-α in the serum were detected by ELISA assay. Results. HFBP could alleviate the inflammation in the lung tissue of mice, decrease the proportion of Th17 cells, and increase the proportion of Treg cells in bronchoalveolar lavage fluid. HFBP could decrease IL-4 and TNF-α level and increase TGF-β level in blood. Conclusion. HFBP could treat the asthma through impacting the balance of Th17 cells and Treg cells as well as the levels of related inflammatory cytokines in asthma mice.

  5. Yupingfeng Pulvis Regulates the Balance of T Cell Subsets in Asthma Mice.

    Science.gov (United States)

    Wang, Zhigang; Cai, Xueting; Pang, Zhonghua; Wang, Dawei; Ye, Juan; Su, Kelei; Sun, Xiaoyan; Li, Jing; Cao, Peng; Hu, Chunping

    2016-01-01

    Background. Yupingfeng Pulvis (HFBP) had played an active role in many diseases, especially respiratory tract infections. Exploring the possible prevention mechanism of HFBP may provide new ideas in clinical applications for this well-known herbal formula. Purpose. To study the possible mechanisms of therapy effect of HFBP on asthma mice via regulating the balance of Tregs and Th17 cells. Method. The female BALB/c mice were divided into five groups: control group, model group, prednisone (5.5 mg/kg) group, and 22 g/kg HFBP and 44 g/kg HFBP groups. Ovalbumin was used to make the asthma model of mice; the drug was ig administered daily after atomization for consecutive 15 d. The mice were killed after the last administration. The paraffin-embedded tissue sections of the lungs were stained by H&E. Tregs and Th17 cells in bronchoalveolar lavage fluid were detected by flow cytometry. IL-4, TGF-β, and TNF-α in the serum were detected by ELISA assay. Results. HFBP could alleviate the inflammation in the lung tissue of mice, decrease the proportion of Th17 cells, and increase the proportion of Treg cells in bronchoalveolar lavage fluid. HFBP could decrease IL-4 and TNF-α level and increase TGF-β level in blood. Conclusion. HFBP could treat the asthma through impacting the balance of Th17 cells and Treg cells as well as the levels of related inflammatory cytokines in asthma mice. PMID:27143988

  6. 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.

  7. 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.

  8. Alteration of B-cell subsets enhances neuroinvasion in mouse scrapie infection.

    Science.gov (United States)

    von Poser-Klein, Christine; Flechsig, Eckhard; Hoffmann, Tanja; Schwarz, Petra; Harms, Harry; Bujdoso, Raymond; Aguzzi, Adriano; Klein, Michael A

    2008-04-01

    Acquired forms of prion diseases or transmissible spongiform encephalopathies are believed to occur following peripheral exposure. Prions initially accumulate in the lymphoid system before spreading to the nervous system, but the underlying mechanisms for prion transfer between the two systems are still elusive. Here we show that ablation of the B-cell-specific transmembrane protein CD19, a coreceptor of the complement system, results in an acceleration of prion neuroinvasion. This appears to be due to an alteration of the follicular dendritic cell (FDC) network within the lymphoid tissue, thereby reducing the distance between FDCs and adjacent nerve fibers that mediate prion neuroinvasion. PMID:18199638

  9. Sub-Sets of Cancer Stem Cells Differ Intrinsically in Their Patterns of Oxygen Metabolism

    OpenAIRE

    Gammon, Luke; Biddle, Adrian; Heywood, Hannah K.; Johannessen, Anne C; Mackenzie, Ian C.

    2013-01-01

    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 CD44high cancer stem cell (CSC) fraction and that epithelial and EMT CSCs a...

  10. A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1.

    NARCIS (Netherlands)

    Pillay, J.; Kamp, V.M.; Hoffen, E. van; Visser, T.; Tak, T.; Lammers, J.W.; Ulfman, L.H.; Leenen, L.P.H.; Pickkers, P.; Koenderman, L.

    2012-01-01

    Suppression of immune responses is necessary to limit damage to host tissue during inflammation, but it can be detrimental in specific immune responses, such as sepsis and antitumor immunity. Recently, immature myeloid cells have been implicated in the suppression of immune responses in mouse models

  11. T Cell Subsets in HIV Infected Patients after Successful Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Rönsholt, Frederikke F; Ostrowski, Sisse Rye; Katzenstein, Terese Lea;

    2012-01-01

    Immune activation is decreased by combination antiretroviral therapy (cART) in patients infected with human immunodeficiency virus (HIV), but residual activation remains and has been proposed as a cause of premature aging and death, but data are lacking. We analyzed the relationship between T-cell...

  12. A subset of human plasmacytoid dendritic cells expresses CD8α upon exposure to herpes simplex virus type 1.

    Science.gov (United States)

    Schuster, Philipp; Thomann, Sabrina; Werner, Maren; Vollmer, Jörg; Schmidt, Barbara

    2015-01-01

    Classical and plasmacytoid dendritic cells (DC) play important roles in the defense against murine and human infections with herpes simplex virus (HSV). So far, CD8α expression has only been reported for murine DC. CD8α(+) DC have prominent cross-presenting activities, which are enhanced by murine CD8α(+) PDC. The human orthologue of murine CD8α(+) DC, the CD141 (BDCA3)(+) DC, mainly cross-present after TLR3 ligation. We report here the serendipitous finding that a subset of human PDC upregulates CD8α upon HSV-1 stimulation, as shown by gene array and flow cytometry analyses. CD8α, not CD8ß, was expressed upon exposure. Markers of activation, migration, and costimulation were upregulated on CD8α-expressing human PDC. In these cells, increased cytokine and chemokine levels were detected that enhance development and function of T, B, and NK cells, and recruit immature DC, monocytes, and Th1 cells, respectively. Altogether, human CD8α(+) PDC exhibit a highly activated phenotype and appear to recruit other immune cells to the site of inflammation. Further studies will show whether CD8α-expressing PDC contribute to antigen cross-presentation, which may be important for immune defenses against HSV infections in vitro and in vivo. PMID:26082771

  13. Wash functions downstream of Rho1 GTPase in a subset of Drosophila immune cell developmental migrations

    OpenAIRE

    Verboon, Jeffrey M; Travis K Rahe; Rodriguez-Mesa, Evelyn; Parkhurst, Susan M.

    2015-01-01

    Drosophila immune cells, the hemocytes, undergo four stereotypical developmental migrations to populate the embryo, where they provide immune reconnoitering, as well as a number of non–immune-related functions necessary for proper embryogenesis. Here, we describe a role for Rho1 in one of these developmental migrations in which posteriorly located hemocytes migrate toward the head. This migration requires the interaction of Rho1 with its downstream effector Wash, a Wiskott–Aldrich syndrome fa...

  14. Alteration of B-cell subsets enhances neuroinvasion in mouse scrapie infection

    OpenAIRE

    von Poser-Klein, C; Flechsig, E.; Hoffmann, T.; Schwarz, P.; Harms, H.; Bujdoso, R; Aguzzi, A; Klein, M A

    2008-01-01

    Acquired forms of prion diseases or transmissible spongiform encephalopathies are believed to occur following peripheral exposure. Prions initially accumulate in the lymphoid system before spreading to the nervous system, but the underlying mechanisms for prion transfer between the two systems are still elusive. Here we show that ablation of the B-cell-specific transmembrane protein CD19, a coreceptor of the complement system, results in an acceleration of prion neuroinvasion. This appears to...

  15. Yupingfeng Pulvis Regulates the Balance of T Cell Subsets in Asthma Mice

    OpenAIRE

    Zhigang Wang; Xueting Cai; Zhonghua Pang; Dawei Wang; Juan Ye; Kelei Su; Xiaoyan Sun; Jing Li; Peng Cao; Chunping Hu

    2016-01-01

    Background. Yupingfeng Pulvis (HFBP) had played an active role in many diseases, especially respiratory tract infections. Exploring the possible prevention mechanism of HFBP may provide new ideas in clinical applications for this well-known herbal formula. Purpose. To study the possible mechanisms of therapy effect of HFBP on asthma mice via regulating the balance of Tregs and Th17 cells. Method. The female BALB/c mice were divided into five groups: control group, model group, prednisone (5.5...

  16. Plant Proteases Involved in Regulated Cell Death.

    Science.gov (United States)

    Zamyatnin, A A

    2015-12-01

    Each plant genome encodes hundreds of proteolytic enzymes. These enzymes can be divided into five distinct classes: cysteine-, serine-, aspartic-, threonine-, and metalloproteinases. Despite the differences in their structural properties and activities, members of all of these classes in plants are involved in the processes of regulated cell death - a basic feature of eukaryotic organisms. Regulated cell death in plants is an indispensable mechanism supporting plant development, survival, stress responses, and defense against pathogens. This review summarizes recent advances in studies of plant proteolytic enzymes functioning in the initiation and execution of distinct types of regulated cell death. PMID:26878575

  17. 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.

  18. 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

    Background: Major histocompatibility complex (MHC) class I peptide binding and presentation are essential for antigen-specific activation of cytotoxic T lymphocytes (CTLs) and swine MHC class I molecules, also termed swine leukocyte antigens (SLA), thus play a crucial role in the process that leads...... 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 CD...

  19. Identification and characterization of a tumor infiltrating CD56(+)/CD16 (-) NK cell subset with specificity for pancreatic and prostate cancer cell lines.

    Science.gov (United States)

    Frankel, Timothy L; Burns, William; Riley, John; Morgan, Richard A; Davis, Jeremy L; Hanada, Kenichi; Quezado, Martha; Rosenberg, Steven A; Royal, Richard E

    2010-12-01

    In a recent clinical trial, a patient exhibited regression of several pancreatic cancer metastases following the administration of the immune modulator Ipilimumab (anti-CTLA-4 antibody). We sought to characterize the immune cells responsible for this regression. Tumor infiltrating lymphocytes (TIL-2742) and an autologous tumor line (TC-2742) were expanded from a regressing metastatic lesion excised from this patient. Natural killer (NK) cells predominated in the TIL (92% CD56(+)) with few T cells (12% CD3(+)). A majority (88%) of the NK cells were CD56(bright)CD16(-). TIL-2742 secreted IFN-γ and GM-CSF following co-culture with TC-2742 and major histocompatibility complex mismatched pancreatic tumor lines. After sorting TIL-2742, the purified CD56(+)CD16(-)CD3(-) subset showed reactivity similar to TIL-2742 while the CD56(-)CD16(-)CD3(+) cells exhibited no tumor recognition. In co-culture assays, TIL-2742 and the NK subset expressed high reactivity to several pancreatic and prostate cancer cell lines and could lyse the autologous tumor as well as pancreas and prostate cancer lines. Reactivity was partially abrogated by blockade of TRAIL. We thus identified a unique subset of NK cells (CD56(bright)CD16(dim)) isolated from a regressing metastatic pancreatic cancer in a patient responding to Ipilimumab. This represents the first report of CD56(+)CD16(-) NK cells with apparent specificity for pancreatic and prostate cancer cell lines and associated with tumor regression following the treatment with an immune modulating agent. PMID:20734041

  20. CXCR3 expression defines a novel subset of innate CD8+ T cells that enhance immunity against bacterial infection and cancer upon stimulation with IL-15.

    Science.gov (United States)

    Oghumu, Steve; Terrazas, Cesar A; Varikuti, Sanjay; Kimble, Jennifer; Vadia, Stephen; Yu, Lianbo; Seveau, Stephanie; Satoskar, Abhay R

    2015-03-01

    Innate CD8(+) T cells are a heterogeneous population with developmental pathways distinct from conventional CD8(+) T cells. However, their biology, classification, and functions remain incompletely understood. We recently demonstrated the existence of a novel population of chemokine (C-X-C motif) receptor 3 (CXCR3)-positive innate CD8(+) T cells. Here, we investigated the functional properties of this subset and identified effector molecules and pathways which mediate their function. Adoptive transfer of IL-15 activated CXCR3(+) innate CD8(+) T cells conferred increased protection against Listeria monocytogenes infection in susceptible IFN-γ(-/-) mice compared with similarly activated CXCR3(-) subset. This was associated with enhanced proliferation and IFN-γ production in CXCR3(+) cells. Further, CXCR3(+) innate cells showed enhanced cytotoxicity against a tumor cell line in vitro. In depth analysis of the CXCR3(+) subset showed increased gene expression of Ccl5, Klrc1, CtsW, GP49a, IL-2Rβ, Atp5e, and Ly6c but reduced IFN-γR2 and Art2b. Ingenuity pathway analysis revealed an up-regulation of genes associated with T-cell activation, proliferation, cytotoxicity, and translational initiation in CXCR3(+) populations. Our results demonstrate that CXCR3 expression in innate CD8(+) T cells defines a subset with enhanced cytotoxic potential and protective antibacterial immune functions. Immunotherapeutic approaches against infectious disease and cancer could utilize CXCR3(+) innate CD8(+) T-cell populations as novel clinical intervention strategies. PMID:25466888

  1. 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. PMID:26089205

  2. 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

  3. 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

  4. CD103 marks a subset of human CD34+-derived langerin+ dendritic cells that induce T-regulatory cells via indoleamine 2,3-dioxygenase-1.

    Science.gov (United States)

    Očadlíková, Darina; Trabanelli, Sara; Salvestrini, Valentina; Ciciarello, Marilena; Evangelisti, Cecilia; Lecciso, Mariangela; Sabattini, Elena; Righi, Simona; Piccioli, Milena; Pileri, Stefano A; Lemoli, Roberto M; Curti, Antonio

    2015-04-01

    Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive molecule expressed in some subsets of normal and neoplastic cells. Mature human dendritic cells (DCs) have been shown to express IDO1, but little is known about its expression and function during DC differentiation from bone marrow hematopoietic stem/progenitor cells (HSPCs). Here, we show that during in vitro differentiation along the myeloid DC lineage, CD34(+) HSPCs acquire IDO1 expression, which acts in a tolerogenic manner by inducing a population of fully functional CD4(+)CD25(+) FOXP3(+) T-regulatory cells. Phenotypically, CD1a(+)CD14(-) HPSC-derived DCs expressed IDO1, langerin, CD11b, and CD1c. Cell-sorting experiments demonstrated that IDO1 expression is found in a subset of CD1a(+)CD14(-)langerin(+) cells, expressing CD103, which is capable of inducing T-regulatory cells in an IDO1-dependent manner. In conclusion, DC differentiation from CD34(+) HSPCs results in the expression of a functionally active IDO1 protein in CD1a(+)langerin(+), CD103-expressing DCs. These data point toward IDO1 expression as part of a tolerogenic signature during DC development. PMID:25584868

  5. Langerhans cell histiocytosis with multiple spinal involvement

    OpenAIRE

    Jiang, Liang; Liu, Xiao Guang; Zhong, Wo Quan; Ma, Qing Jun; Wei, Feng; Yuan, Hui Shu; Dang, Geng Ting; Liu, Zhong Jun

    2010-01-01

    To stress the clinical and radiologic presentation and treatment outcome of Langerhans cell histiocytosis (LCH) with multiple spinal involvements. A total of 42 cases with spinal LCH were reviewed in our hospital and 5 had multifocal spinal lesions. Multiple spinal LCH has been reported in 50 cases in the literature. All cases including ours were analyzed concerning age, sex, clinical and radiologic presentation, therapy and outcome. Of our five cases, three had neurological symptom, four sof...

  6. 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.

  7. Clinical significance of determination of changes of serum TNF-α, IFN-γ and T-cell subsets distribution pattern in pediatric patients with aplastic anemia

    International Nuclear Information System (INIS)

    Objective: To explore the changes of serum TNF-α, IFN-γ and T-cell subsets distribution pattern in pediatric patients with aplastic anemia. Methods: Serum TNF-α levels (with RIA), IFN-γ levels (with ELISA), peripheral blood T-cell subsets distribution pattern (with monoclonal antibody technique) were determined in 33 pediatric patients with aplastic anemia, as well as in 35 controls. Results: The serum levels of TNF-α and IFN-γ in the patients with aplastic anemia were significantly higher than those in the controls (P<0.01), while the CD3, CD4 percentages and CD4/CD8 ratio were significantly lower (P<0.01). Conclusion: Detection of changes of serum TNF-α, IFN-γ levels and T-cell subsets ratio was clinically useful for outcome prediction in pediatric patients with aplastic anemia. (authors)

  8. Clinical significance of determination of changes of serum SOD, TNF-α levels and T-cell subsets distribution type after treatment in pediatric patients with acute bronchitis

    International Nuclear Information System (INIS)

    Objective: To study the changes of serum SOD, TNF-α levels and T-cell subsets distribution type after treatment in pediatric patients with acute bronchitis. Methods: Serum SOD, TNF-α levels (with RIA) and T-cell subsets distribution type (with monoclonal antibody technique) were detected both before and after treatment in 39 pediatric patients with acute bronchitis as well as in 35 controls. Results: Before treatment, the serum levels of SOD, CD4/CD8 ratios were significantly lower and serum TNF-α levels significantly higher in the patients than those in the controls (P0.05). Conclusion: Determination of serum SOD, TNF-α levels and T-cell subsets distribution type is clinically meaningful in pediatric patients with acute bronchitis. (authors)

  9. Clinical significance of determination of changes of serum SOD, TNF, CRP levels and T-cell subsets distribution type after treatment in aged patients with chronic bronchitis

    International Nuclear Information System (INIS)

    Objective: To investigate the changes of serum SOD, TNF, CRP levels and T-cell subsets distribution type after treatment in aged patients with chronic bronchitis. Methods: Serum SOD, TNF levels (with RIA), CRP levels (with biochemistry) and T-cell subsets distribution type (with monoclonal antibody) were detected both before and after treatment in 42 aged patients with chronic bronchitis as well as in 35 controls. Results: Before treatment, the serum levels of SOD, CD4/CD8 ratios were significantly lower and serum TNF, CRP levels significantly higher in the patients than those in the controls (P4/CD8 ratios remained significantly higher than those in controls (P <0.05). Conclusion: Determination of serum SOD, TNF, CRP levels and T-cell subsets distribution type is clinically meaningful in aged patients with chronic bronchitis. (authors)

  10. Fingolimod therapy modulates circulating B cell composition, increases B regulatory subsets and production of IL-10 and TGFβ in patients with Multiple Sclerosis.

    Science.gov (United States)

    Blumenfeld, Shiri; Staun-Ram, Elsebeth; Miller, Ariel

    2016-06-01

    Fingolimod, an oral therapeutic agent approved for patients with relapsing-remitting Multiple Sclerosis (MS), has been shown to prevent lymphocyte egress from secondary lymphoid tissues; however the specific drug effect on B cells in fingolimod-treated patients remains to be fully elucidated. We present here a comprehensive analysis on the proportions of B cell subsets in the periphery, and the levels of activation, functional surface markers and cytokine profile of B cells in MS patients, following initiation of fingolimod therapy, using flow cytometry and cytokine bead array. Fingolimod therapy increased the ratio of naïve to memory cells, elevated the percentage of plasma cells and highly increased the proportion of transitional B cells as well as additional regulatory subsets, including: IL10(+), CD25(+) and CD5(+) B cells. The percentage of activated CD69(+) cells was highly elevated in the remaining circulating B cells, which produced increased levels of IL10, TGFβ, IL6, IL4, LTα, TNFα and IFNγ cytokines, with an overall increased ratio of TGFβ to pro-inflammatory cytokines. Furthermore, fingolimod therapy reduced ICAM-1(+) cells, suggesting a possible reduction in antigen-presenting capacity. Phosphorylated-fingolimod was shown in vitro to reduce S1PR1 RNA and protein, to slightly increase viability and to activate anti-apoptotic Bcl2 in transformed B cells of patients with MS. In conclusion, fingolimod therapy modulates significantly the composition of circulating B cells, promoting regulatory subsets and an anti-inflammatory cytokine repertoire. PMID:27055778

  11. 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

  12. 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.

  13. 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.

  14. Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study

    Directory of Open Access Journals (Sweden)

    Dobbs R

    2012-10-01

    Full Text Available Abstract Background Following Helicobacter pylori eradication in idiopathic parkinsonism (IP, hypokinesia improved but flexor-rigidity increased. Small intestinal bacterial-overgrowth (SIBO is a candidate driver of the rigidity: hydrogen-breath-test-positivity is common in IP and case histories suggest that Helicobacter keeps SIBO at bay. Methods In a surveillance study, we explore relationships of IP-facets to peripheral immune/inflammatory-activation, in light of presence/absence of Helicobacter infection (urea-breath- and/or stool-antigen-test: positivity confirmed by gastric-biopsy and hydrogen-breath-test status for SIBO (positivity: >20 ppm increment, 2 consecutive 15-min readings, within 2h of 25G lactulose. We question whether any relationships found between facets and blood leukocyte subset counts stand in patients free from anti-parkinsonian drugs, and are robust enough to defy fluctuations in performance consequent on short t½ therapy. Results Of 51 IP-probands, 36 had current or past Helicobacter infection on entry, 25 having undergone successful eradication (median 3.4 years before. Thirty-four were hydrogen-breath-test-positive initially, 42 at sometime (343 tests during surveillance (2.8 years. Hydrogen-breath-test-positivity was associated inversely with Helicobacter-positivity (OR 0.20 (95% CI 0.04, 0.99, p In 38 patients (untreated (17 or on stable long-t½ IP-medication, the higher the natural-killer count, the shorter stride, slower gait and greater flexor-rigidity (by mean 49 (14, 85 mm, 54 (3, 104 mm.s-1, 89 (2, 177 Nm.10-3, per 100 cells.μl-1 increment, p=0.007, 0.04 & 0.04 respectively, adjusted for patient characteristics. T-helper count was inversely associated with flexor-rigidity before (p=0.01 and after adjustment for natural-killer count (-36(-63, -10 Nm.10-3 per 100 cells.μl-1, p=0.007. Neutrophil count was inversely associated with tremor (visual analogue scale, p=0.01. Effect-sizes were independent of IP

  15. CXCR3 expression defines a novel subset of innate CD8+ T cells that enhance immunity against bacterial infection and cancer upon stimulation with IL-15

    OpenAIRE

    Oghumu, Steve; Terrazas, Cesar A.; Varikuti, Sanjay; Kimble, Jennifer; Vadia, Stephen; Yu, Lianbo; Seveau, Stephanie; Abhay R Satoskar

    2014-01-01

    Innate CD8+ T cells are a heterogeneous population with developmental pathways distinct from conventional CD8+ T cells. However, their biology, classification, and functions remain incompletely understood. We recently demonstrated the existence of a novel population of chemokine (C-X-C motif) receptor 3 (CXCR3)-positive innate CD8+ T cells. Here, we investigated the functional properties of this subset and identified effector molecules and pathways which mediate their function. Adoptive trans...

  16. Immunophenotyping of lymphocyte, monocyte and dendritic cell subsets in normal rhesus macaques by 12-color flow cytometry: Clarification on DC heterogeneity

    OpenAIRE

    Autissier, Patrick; Soulas, Caroline; Burdo, Tricia H.; Williams, Kenneth C.

    2010-01-01

    Monitoring changes in rhesus macaque immune cell populations during infectious disease is crucial. The aim of this work was to simultaneously analyze the phenotype of rhesus macaque lymphocyte, monocyte and dendritic cell (DC) subsets using a single 12-color flow cytometry panel. Blood from healthy non-infected rhesus macaques was labeled with a cocktail of 12 antibodies. Data were compared to three smaller lineage specific panels and absolute and relative percentages of cells were compared. ...

  17. Characterisation of an epigenetically altered CD4+ CD28+ Kir+ T cell subset in autoimmune rheumatic diseases by multiparameter flow cytometry

    Science.gov (United States)

    Strickland, Faith M; Patel, Dipak; Somers, Emily; Robida, Aaron M; Pihalja, Michael; Swartz, Richard; Marder, Wendy; Richardson, Bruce

    2016-01-01

    Objectives Antigen-specific CD4+ T cells epigenetically modified with DNA methylation inhibitors overexpress genes normally suppressed by this mechanism, including CD11a, CD70, CD40L and the KIR gene family. The altered cells become autoreactive, losing restriction for nominal antigen and responding to self-class II major histocompatibility complex (MHC) molecules without added antigen, and are sufficient to cause a lupus-like disease in syngeneic mice. T cells overexpressing the same genes are found in patients with active lupus. Whether these genes are co-overexpressed on the same or different cells is unknown. The goal of this study was to determine whether these genes are overexpressed on the same or different T cells and whether this subset of CD4+ T cells is also present in patients with lupus and other rheumatic diseases. Methods Multicolour flow cytometry was used to compare CD11a, CD70, CD40L and KIR expression on CD3+CD4+CD28+ T cells to their expression on experimentally demethylated CD3+CD4+CD28+ T cells and CD3+CD4+CD28+ T cells from patients with active lupus and other autoimmune diseases. Results Experimentally demethylated CD4+ T cells and T cells from patients with active lupus have a CD3+CD4+CD28+CD11ahiCD70+CD40LhiKIR+ subset, and the subset size is proportional to lupus flare severity. A similar subset is found in patients with other rheumatic diseases including rheumatoid arthritis, systemic sclerosis and Sjögren's syndrome but not retroperitoneal fibrosis. Conclusions Patients with active autoimmune rheumatic diseases have a previously undescribed CD3+CD4+CD28+CD11ahiCD70+CD40LhiKIR+ T cell subset. This subset may play an important role in flares of lupus and related autoimmune rheumatic diseases, provide a biomarker for disease activity and serve as a novel therapeutic target for the treatment of lupus flares. PMID:27099767

  18. 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; Ryder, L P; Platz, P; Lindhardt, B O; Lundgren, Jens Dilling

    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...

  19. 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 be...

  20. Endothelial cells' activation and apoptosis induced by a subset of antibodies against human cytomegalovirus: relevance to the pathogenesis of atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Claudio Lunardi

    Full Text Available BACKGROUND: Human cytomegalovirus (hCMV is involved in the pathogenesis of atherosclerosis. We have previously shown in patients with atherosclerosis that antibodies directed against the hCMV-derived proteins US28 and UL122 are able to induce endothelial cell damage and apoptosis of non-stressed endothelial cells through cross-rection with normally expressed surface molecules. Our aim was to dissect the molecular basis of such interaction and to investigate mechanisms linking innate immunity to atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the gene expression profiles in endothelial cells stimulated with antibodies affinity-purified against either the UL122 or the US28 peptides using the microarray technology. Microarray results were validated by quantitative PCR and by detection of proteins in the medium. Supernatant of endothelial cells incubated with antibodies was analysed also for the presence of Heat Shock Protein (HSP60 and was used to assess stimulation of Toll-Like Receptor-4 (TLR4. Antibodies against UL122 and US28 induced the expression of genes encoding for adhesion molecules, chemokines, growth factors and molecules involved in the apoptotis process together with other genes known to be involved in the initiation and progression of the atherosclerotic process. HSP60 was released in the medium of cells incubated with anti-US28 antibodies and was able to engage TLR4. CONCLUSIONS/SIGNIFICANCE: Antibodies directed against hCMV modulate the expression of genes coding for molecules involved in activation and apoptosis of endothelial cells, processes known to play a pivotal role in the pathogenesis of atherosclerosis. Moreover, endothelial cells exposed to such antibodies express HSP60 on the cell surface and release HSP60 in the medium able to activate TLR4. These data confirm that antibodies directed against hCMV-derived proteins US28 and UL122 purified from patients with coronary artery disease induce endothelial cell

  1. Langerhans cell histiocytosis with multiple spinal involvement.

    Science.gov (United States)

    Jiang, Liang; Liu, Xiao Guang; Zhong, Wo Quan; Ma, Qing Jun; Wei, Feng; Yuan, Hui Shu; Dang, Geng Ting; Liu, Zhong Jun

    2011-11-01

    To stress the clinical and radiologic presentation and treatment outcome of Langerhans cell histiocytosis (LCH) with multiple spinal involvements. A total of 42 cases with spinal LCH were reviewed in our hospital and 5 had multifocal spinal lesions. Multiple spinal LCH has been reported in 50 cases in the literature. All cases including ours were analyzed concerning age, sex, clinical and radiologic presentation, therapy and outcome. Of our five cases, three had neurological symptom, four soft tissue involvement and three had posterior arch extension. Compiling data from the eight largest case series of the spinal LCH reveals that 27.2% multiple vertebrae lesions. In these 55 cases, there were 26 female and 29 male with the mean age of 7.4 years (range 0.2-37). A total of 182 vertebrae were involved including 28.0% in the cervical spine, 47.8% in thoracic and 24.2% in the lumbar spine. Extraspinal LCH lesion was documented in 54.2% cases, visceral involvement in 31.1% and vertebra plana in 50% cases. Paravertebral and epidural extension were not documented in most cases. Pathological diagnosis was achieved in 47 cases including 8 open spine biopsy. The treatment strategy varied depending on different hospitals. One patient died, two had recurrence and the others had no evidence of the disease with an average of 7.2 years (range 1-21) of follow-up. Asymptomatic spinal lesions could be simply observed with or without bracing and chemotherapy is justified for multiple lesions. Surgical decompression should be reserved for the uncommon cases in which neurologic compromise does not respond to radiotherapy or progresses too rapidly for radiotherapy. PMID:20496040

  2. Effects of cytotoxic T lymphocytes on hepatoma cell line SMMC-7721 induced by different subsets of dendritic cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Jia-Xiang Wang; Guang-Hui Liu; Ying-Zhong Fan; Qiu-Liang Liu; Juan Zhou; Dong-Yun Zhang; Yuan-Ming Qi

    2006-01-01

    BACKGROUND:Dendritic cells (DCs) loaded with complex antigen are always used to induce cytotoxic T lymphocytes (CTLs) which have a speciifc anti-tumor activity. However, CTLs can assault autologous cells induced by DCs loaded with autologous antigen. This study aimed to explore how to weaken the autoimmune reaction induced by DC vaccine by combining mature DC (mDC) activating immunity and immature DC (imDC) leading to immune tolerance to make hepatocellular carcinoma (HCC) vaccine in vitro. METHODS: DC progenitors derived from human peripheral blood were assigned to two groups. One was cultured to mDC and pulsed with frozen-thawed antigen (FTA) of human HCC cell line SMMC-7721 cells (mDC group), and the other was cultured to imDC and pulsed with FTA of human liver cell line L-02 cells (imDC group). The morphology of DCs was monitored and cells phenotypes including HLA-DR, CD80, CD1α, CD83 were assayed by lfowcytometry (FCM). The concentrations of interleukin-12 (IL-12) in the supernatant were assayed by ELISA. Methyl thiazolyl tetrazolium (MTT) was used to evaluate T cell proliferation induced by mDC and imDC and the killing rate of CTL induced by mDC and imDC respectively/together on SMMC-7721 and L-02 cells. RESULTS: Compared with the imDC group, the mDC group was characterized by the following: increased secretion of IL-12 (P0.05). CTL induced by mDC and imDC together had a higher killing response to SMMC-7721, but a lower killing rate for L-02 (P CONCLUSIONS:CTL induced by mDC and imDC together has a higher antigen-speciifc killing response in vitro than that induced by mDC alone. This may be of greater clinical value.

  3. Association between gene and miRNA expression profiles and stereotyped subset #4 B-cell receptor in chronic lymphocytic leukemia.

    Science.gov (United States)

    Maura, Francesco; Cutrona, Giovanna; Mosca, Laura; Matis, Serena; Lionetti, Marta; Fabris, Sonia; Agnelli, Luca; Colombo, Monica; Massucco, Carlotta; Ferracin, Manuela; Zagatti, Barbara; Reverberi, Daniele; Gentile, Massimo; Recchia, Anna Grazia; Bossio, Sabrina; Rossi, Davide; Gaidano, Gianluca; Molica, Stefano; Cortelezzi, Agostino; Di Raimondo, Francesco; Negrini, Massimo; Tassone, Pierfrancesco; Morabito, Fortunato; Ferrarini, Manlio; Neri, Antonino

    2015-01-01

    In this study we investigated specific biological and clinical features associated with chronic lymphocytic leukemia (CLL) patients carrying stereotyped BCR subset #4 (IGHV4-34) among a prospective cohort of 462 CLL/MBL patients in early stage (Binet A). All subset #4 patients (n = 16) were characterized by the IGHV mutated gene configuration, and absence of unfavorable cytogenetic lesions, NOTCH1 or SF3B1 mutations. Gene and miRNA expression profiling evidenced that the leukemic cells of subset #4 cases showed significant downregulation of WDFY4, MF2A and upregulation of PDGFA, FGFR1 and TFEC gene transcripts, as well as the upregulation of miR-497 and miR-29c. The transfection of miR-497 mimic in primary leukemic CLL cells induced a downregulation of BCL2, a known validated target of this miRNA. Our data identify biological characteristics associated with subset #4 patients, providing further evidence for the putative role of BCR in shaping the features of the tumor cells in CLL. PMID:25860243

  4. Clinical significance of determination of changes of TGF-β1 levels and T-cell subset distribution type in patients with hepatic cirrhosis

    International Nuclear Information System (INIS)

    Objective: To explore the changes of serum TGF-β1 levels and T-cell subset distribution types in patients with hepatic cirrhosis. Methods: Serum TGF-β1 levels was measured with RIA and T-cell subset distribution type was studied with monoclonal antibody technique in 64 patients with hepatic cirrhosis and 35 controls. Results: In the patients the serum TGF-β1 and CD8 levels were significantly higher than those in controls (P1 levels were significantly negatively correlated with those of CD4 cells and CD4/CD8 ratio, but significantly positively correlated with those of CD8 cells. Conclusion: Serum TGF-β1 levels increased significantly in patients with hepatic cirrhoses. With cellular immune function decreased, TGF-β1 may restrain cellular immunity, which may be one of the causes of hypo-function of cellular immune system in patients with hepatic cirrhosis. (authors)

  5. 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.

  6. IL-1β regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function

    OpenAIRE

    Elkabets, Moshe; Ribeiro, Vera S. G.; Dinarello, Charles A.; Ostrand-Rosenberg, Suzanne; Di Santo, James P; Apte, Ron N.; Vosshenrich, Christian A J

    2010-01-01

    Chronic inflammation is associated with promotion of malignancy and tumor progression. Many tumors enhance the accumulation of myeloid-derived suppressor cells (MDSC), which contribute to tumor progression and growth by suppressing anti-tumor immune responses. Tumor-derived IL-1β secreted into the tumor microenvironment has been shown to induce the accumulation of MDSC possessing an enhanced capacity to suppress T cells. In this study, we found that the enhanced suppressive potential of IL-1β...

  7. Involvement and prognosis value of CD8(+) T cells in giant cell arteritis.

    Science.gov (United States)

    Samson, Maxime; Ly, Kim Heang; Tournier, Benjamin; Janikashvili, Nona; Trad, Malika; Ciudad, Marion; Gautheron, Alexandrine; Devilliers, Hervé; Quipourt, Valérie; Maurier, François; Meaux-Ruault, Nadine; Magy-Bertrand, Nadine; Manckoundia, Patrick; Ornetti, Paul; Maillefert, Jean-Francis; Besancenot, Jean-François; Ferrand, Christophe; Mesturoux, Laura; Labrousse, François; Fauchais, Anne-Laure; Saas, Philippe; Martin, Laurent; Audia, Sylvain; Bonnotte, Bernard

    2016-08-01

    CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vβ families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed. Among total CD8(+) T cells, percentages of circulating cytotoxic CD8 T lymphocytes (CTL, CD3(+)CD8(+)perforin(+)granzymeB(+)), Tc17 (CD3(+)CD8(+)IL-17(+)), CD63(+)CD8(+) T cells and levels of soluble granzymes A and B were higher in patients than in controls, whereas the percentage of Tc1 cells (CD3(+)CD8(+)IFN-γ(+)) was similar. Moreover, CD8(+) T cells displayed a restricted TCR repertoire in GCA patients. Percentages of circulating CTL, Tc17 and soluble levels of granzymes A and B decreased after treatment. CXCR3 expression on CD8(+) T cells and its serum ligands (CXCL9, -10, -11) were higher in patients. Analyses of TAB revealed high expression of CXCL9 and -10 associated with infiltration by CXCR3(+)CD8(+) T cells expressing granzyme B and TiA1. The intensity of the CD8 T-cell infiltrate in TAB was predictive of the severity of the disease. This study demonstrates the implication and the prognostic value of CD8(+) T-cells in GCA and suggests that CD8(+) T-cells are recruited within the vascular wall through an interaction between CXCR3 and its ligands. PMID:27236507

  8. 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.

  9. Circulating and in situ lymphocyte subsets and Langerhans cells in patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity during treatment with azathioprine

    Energy Technology Data Exchange (ETDEWEB)

    Baadsgaard, O.

    1986-04-01

    Circulating and in situ lymphocyte subsets and Langerhans cells in four patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity before and during treatment with azathioprine were estimated. It was found that the number of Leu 6+ Langerhans cells decreased during therapy. This decrease was accompanied by a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, DR+, and Leu M2+ cells in the blood and a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, and DR+ cells in the skin. Concomitantly with the changes in the number of immunocompetent cells, the eczema cleared.

  10. Circulating and in situ lymphocyte subsets and Langerhans cells in patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity during treatment with azathioprine

    International Nuclear Information System (INIS)

    Circulating and in situ lymphocyte subsets and Langerhans cells in four patients with compositae oleoresin dermatitis and increased ultraviolet A sensitivity before and during treatment with azathioprine were estimated. It was found that the number of Leu 6+ Langerhans cells decreased during therapy. This decrease was accompanied by a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, DR+, and Leu M2+ cells in the blood and a reduction in the number of Leu 2a+, Leu 3a+, Leu 4+, and DR+ cells in the skin. Concomitantly with the changes in the number of immunocompetent cells, the eczema cleared

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

    Science.gov (United States)

    Andrews, T. Daniel; Jeelall, Yogesh; Talaulikar, Dipti; Goodnow, Christopher C.

    2016-01-01

    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 artefactual sequence

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

    Science.gov (United States)

    Andrews, T Daniel; Jeelall, Yogesh; Talaulikar, Dipti; Goodnow, Christopher C; Field, Matthew A

    2016-01-01

    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 artefactual sequence

  13. Cutting edge: identification of the thymic stromal lymphopoietin-responsive dendritic cell subset critical for initiation of type 2 contact hypersensitivity.

    Science.gov (United States)

    Kitajima, Masayuki; Ziegler, Steven F

    2013-11-15

    The cytokine thymic stromal lymphopoietin (TSLP) has been implicated in the initiation and progression of allergic inflammation through its ability to activate dendritic cells (DCs). However, the identity of the DC subset that responds to TSLP is not known. In this study we use a CCL17 reporter strain to identify the TSLP-responsive DC subset. In vitro, TSLP induced CD11b(high) DCs to express CCL17, to increase CCR7-mediated migration activity, and to drive Th2 differentiation of naive CD4 T cells. In vivo, following skin sensitization, we found that a subset of Ag-bearing CCL17(+)CD11b(high) migratory DCs, but not Ag-bearing CCL17(-) migratory DCs, in skin lymph nodes were capable of driving Th2 differentiation and were dramatically reduced in TSLPR-deficient mice. Taken together, these results demonstrate that TSLP activated a subset of CD11b(+) DCs in the skin to produce CCL17, upregulate CCR7, and migrate to the draining lymph node to initiate Th2 differentiation. PMID:24123684

  14. 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.

  15. Cranial involvement in sickle cell disease

    International Nuclear Information System (INIS)

    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.

  16. 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.

  17. 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.

  18. 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; Plesner, T

    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...... "autologous" mixed lymphocyte reaction. In addition, the immunoadsorbent method very efficiently selects Tcr/CD-3- variants from mutagenized Jurkat cell populations incubated with anti-CD3 mAb. The described method is easy and quick and can fractionate large numbers of cells; it is the "poor-man's cell sorter...... 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, and the...

  19. Are hematopoietic stem cells involved in hepatocarcinogenesis?

    OpenAIRE

    Facciorusso, Antonio; Antonino, Matteo; Del Prete, Valentina; Neve, Viviana; Scavo, Maria Principia; Barone, Michele

    2014-01-01

    The liver has three cell lineages able to proliferate after a hepatic injury: the mature hepatocyte, the ductular “bipolar” progenitor cell termed “oval cell” and the putative periductular stem cell. Hepatocytes can only produce other hepatocytes whereas ductular progenitor cells are considerate bipolar since they can give rise to biliary cells or hepatocytes. Periductular stem cells are rare in the liver, have a very long proliferation potential and may be multipotent, being this aspect stil...

  20. 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.

  1. Clinical significance of determination of changes of serum TGF-β1 levels and t-cell subset distribution type in patients with gastric ulcer

    International Nuclear Information System (INIS)

    Objective: To study the changes of serum TGF-β1 levels and T-cell subset distribution type in patients with gastric ulcer. Methods: Serum TGF-β1 levels were measured with RIA and T-cell subset distribution type was studied with monoclonal antibody technique in 32 patients with gastric ulcer and 35 controls. Results: In the patients,the serum TGF-β1 levels and CD8 percentage were significantly higher than those in controls (P1 levels were significantly negatively correlated with CD4 percentage and CD4/CD8 ratio, but significantly positively correlated with CD8 percentage. Conclusion: Serum TGF-β1 may inhibit cellular immunity, which may be one of the causes of reduced cellular immuno-function in patients with gastric ulcer. (authors)

  2. 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.

  3. 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.

    Science.gov (United States)

    Goudin, Nicolas; Chappert, Pascal; Mégret, Jérome; Gross, David-Alexandre; Rocha, Benedita; Azogui, Orly

    2016-01-01

    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. PMID:27341421

  4. 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.

  5. 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

  6. Signaling involved in stem cell reprogramming and differentiation

    OpenAIRE

    Tanabe, Shihori

    2015-01-01

    Stem cell differentiation is regulated by multiple signaling events. Recent technical advances have revealed that differentiated cells can be reprogrammed into stem cells. The signals involved in stem cell programming 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 s...

  7. 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.

  8. A functional family-wide screening of SP/KLF proteins identifies a subset of suppressors of KRAS-mediated cell growth.

    Science.gov (United States)

    Fernandez-Zapico, Martin E; Lomberk, Gwen A; Tsuji, Shoichiro; DeMars, Cathrine J; Bardsley, Michael R; Lin, Yi-Hui; Almada, Luciana L; Han, Jing-Jing; Mukhopadhyay, Debabrata; Ordog, Tamas; Buttar, Navtej S; Urrutia, Raul

    2011-04-15

    SP/KLF (Specificity protein/Krüppel-like factor) transcription factors comprise an emerging group of proteins that may behave as tumour suppressors. Incidentally, many cancers that display alterations in certain KLF proteins are also associated with a high incidence of KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homologue) mutations. Therefore in the present paper we investigate whether SP/KLF proteins suppress KRAS-mediated cell growth, and more importantly, the potential mechanisms underlying these effects. Using a comprehensive family-wide screening of the 24 SP/KLF members, we discovered that SP5, SP8, KLF2, KLF3, KLF4, KLF11, KLF13, KLF14, KLF15 and KLF16 inhibit cellular growth and suppress transformation mediated by oncogenic KRAS. Each protein in this subset of SP/KLF members individually inhibits BrdU (5-bromo-2-deoxyuridine) incorporation in KRAS oncogenic-mutant cancer cells. SP5, KLF3, KLF11, KLF13, KLF14 and KLF16 also increase apoptosis in these cells. Using KLF11 as a representative model for mechanistic studies, we demonstrate that this protein inhibits the ability of cancer cells to form both colonies in soft agar and tumour growth in vivo. Molecular studies demonstrate that these effects of KLF11 are mediated, at least in part, through silencing cyclin A via binding to its promoter and leading to cell-cycle arrest in S-phase. Interestingly, similar to KLF11, KLF14 and KLF16 mechanistically share the ability to modulate the expression of cyclin A. Collectively, the present study stringently defines a distinct subset of SP/KLF proteins that impairs KRAS-mediated cell growth, and that mechanistically some members of this subset accomplish this, at least in part, through regulation of the cyclin A promoter. PMID:21171965

  9. A novel subset of mouse NKT cells bearing the IL-17 receptor B responds to IL-25 and contributes to airway hyperreactivity

    OpenAIRE

    Terashima, Asuka; Watarai, Hiroshi; Inoue, Sayo; Sekine, Etsuko; Nakagawa, Ryusuke; Hase, Koji; Iwamura, Chiaki; Nakajima, Hiroshi; Nakayama, Toshinori; Taniguchi, Masaru

    2008-01-01

    Airway hypersensitive reaction (AHR) is an animal model for asthma, which is caused or enhanced by environmental factors such as allergen exposure. However, the precise mechanisms that drive AHR remain unclear. We identified a novel subset of natural killer T (NKT) cells that expresses the interleukin 17 receptor B (IL-17RB) for IL-25 (also known as IL-17E) and is essential for the induction of AHR. IL-17RB is preferentially expressed on a fraction of CD4+ NKT cells but not on other splenic l...

  10. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane: correlation with transcriptome profiling of neutrophil precursors.

    Science.gov (United States)

    Rørvig, Sara; Østergaard, Ole; Heegaard, Niels H H; Borregaard, Niels

    2013-10-01

    Neutrophils are indispensable in the innate immune defense against invading microorganisms. Neutrophils contain SVs and several subsets of granules that are essential for their function. Proteins present in neutrophil SVs and granules are synthesized during terminal granulopoiesis in the bone marrow. The heterogeneity of granules, as determined by marker proteins characteristic of each granule subset, is thought to result from differences in the biosynthetic windows of major classes of granule proteins, a process referred to as targeting by timing. Qualitative proteomic analysis of neutrophil 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-gel-digested with trypsin. The resulting peptides were analyzed using LTQ Orbitrap XL tandem MS. A total of 1292 unique proteins were identified and grouped, according to the neutrophil fraction, in which they displayed maximal expression. In addition to various known neutrophil proteins, several uncharacterized proteins were found, as well as proteins not described previously in neutrophils. To study the correlation between mRNA expression in neutrophil precursors and the localization of their cognate proteins, the distribution of 126 identified proteins was compared with their mRNA expression profiles. The neutrophil subcellular proteome profiles presented here may be used as a database in combination with the mRNA array database to predict and test the presence and localization of proteins in neutrophil granules and membranes. PMID:23650620

  11. Myosin is involved in postmitotic cell spreading

    OpenAIRE

    1995-01-01

    We have investigated a role for myosin in postmitotic Potoroo tridactylis kidney (PtK2) cell spreading by inhibitor studies, time- lapse video microscopy, and immunofluorescence. We have also determined the spatial organization and polarity of actin filaments in postmitotic spreading cells. We show that butanedione monoxime (BDM), a known inhibitor of muscle myosin II, inhibits nonmuscle myosin II and myosin V adenosine triphosphatases. BDM reversibly inhibits PtK2 postmitotic cell spreading....

  12. Spleen-resident CD4+ and CD4- CD8α- dendritic cell subsets differ in their ability to prime invariant natural killer T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Emilie Bialecki

    Full Text Available One important function of conventional dendritic cells (cDC is their high capacity to capture, process and present Ag to T lymphocytes. Mouse splenic cDC subtypes, including CD8α(+ and CD8α(- cDC, are not identical in their Ag presenting and T cell priming functions. Surprisingly, few studies have reported functional differences between CD4(- and CD4(+ CD8α(- cDC subsets. We show that, when loaded in vitro with OVA peptide or whole protein, and in steady-state conditions, splenic CD4(- and CD4(+ cDC are equivalent in their capacity to prime and direct CD4(+ and CD8(+ T cell differentiation. In contrast, in response to α-galactosylceramide (α-GalCer, CD4(- and CD4(+ cDC differentially activate invariant Natural Killer T (iNKT cells, a population of lipid-reactive non-conventional T lymphocytes. Both cDC subsets equally take up α-GalCer in vitro and in vivo to stimulate the iNKT hybridoma DN32.D3, the activation of which depends solely on TCR triggering. On the other hand, and relative to their CD4(+ counterparts, CD4(- cDC more efficiently stimulate primary iNKT cells, a phenomenon likely due to differential production of co-factors (including IL-12 by cDC. Our data reveal a novel functional difference between splenic CD4(+ and CD4(- cDC subsets that may be important in immune responses.

  13. High frequency of circulating ¿d T cells with dominance of the vd1 subset in a healthy population

    DEFF Research Database (Denmark)

    Hviid, L; Akanmori, B D; Loizon, S;

    2000-01-01

    TCR gamma delta(+) cells constitute <5% of all circulating T cells in healthy, adult Caucasians, and V(delta)1(+) cells constitute a minority of these cells. In contrast to TCR alpha beta(+) cells, their repertoire is selected extrathymically by environmental antigens. Although increased frequenc...

  14. Activation-induced cytidine deaminase expression in CD4+ T cells is associated with a unique IL-10-producing subset that increases with age.

    Directory of Open Access Journals (Sweden)

    Hongyan Qin

    Full Text Available Activation-induced cytidine deaminase (AID, produced by the Aicda gene, is essential for the immunoglobulin gene (Ig alterations that form immune memory. Using a Cre-mediated genetic system, we unexpectedly found CD4(+ T cells that had expressed Aicda (exAID cells as well as B cells. ExAID cells increased with age, reaching up to 25% of the CD4(+ and B220(+ cell populations. ExAID B cells remained IgM(+, suggesting that class-switched memory B cells do not accumulate in the spleen. In T cells, AID was expressed in a subset that produced IFN-γ and IL-10 but little IL-4 or IL-17, and showed no evidence of genetic mutation. Interestingly, the endogenous Aicda expression in T cells was enhanced in the absence of B cells, indicating that the process is independent from the germinal center reaction. These results suggest that in addition to its roles in B cells, AID may have previously unappreciated roles in T-cell function or tumorigenesis.

  15. A global look into human T cell subsets before and after cryopreservation using multiparametric flow cytometry and two-dimensional visualization analysis.

    Science.gov (United States)

    Lemieux, Jennifer; Jobin, Christine; Simard, Carl; Néron, Sonia

    2016-07-01

    The cryopreservation of human lymphocytes is an essential step for the achievement of several cellular therapies. Besides, T cells are considered as promising actors in cancer therapy for their cytotoxic and regulatory properties. Consequently, the development of tools to monitor the impact of freezing and thawing processes on their fine distribution may be an asset to achieve quality control in cellular therapy. In this study, the phenotypes of freshly isolated human mononuclear cells were compared to those observed following one cycle of cryopreservation and rest periods 0h, 1h and 24h after thawing but before staining. T cells were scrutinized for their distribution according to naive, memory effector, regulatory and helper subsets. Flow cytometry analyses were done using eight-color antibody panels as proposed by the Human Immunophenotyping Consortium. Data were further analyzed by using conventional directed gating and clustering software, namely SPADE and viSNE. Overall, SPADE and viSNE tools were very efficient to monitor the outcome of PBMC populations and T cell subsets. T cells were more sensitive to cryopreservation than other cells. Our results indicated that submitting the thawed cells to a 1h rest period improved the detection of some cell markers when compared to fresh samples. In contrast, cells submitted to a 24h rest period, or to none, were less representative of fresh sample distribution. The heterogeneity of PBMC, as well as the effects of freeze-thaw cycle on their distribution, can be easily monitored by using SPADE and viSNE. PMID:27129808

  16. 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

    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...... (CNS). However, as in other tissues, neuroinflammation can have beneficial as well as pathological outcomes. The complex role of encephalitogenic T cells in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE) may derive from heterogeneity of the myeloid cells with...... three populations of myeloid cells: CD11c(+) microglia, CD11c(-) microglia, and CD11c(+) blood-derived cells in terms of their pathological versus protective functions in the CNS of mice with EAE. Our data show that CNS-resident microglia include functionally distinct subsets that can be distinguished...

  17. Activation, Immune Polarization, and Graft-versus-Leukemia Activity of Donor T-cells are Regulated by Specific Subsets of Donor Bone Marrow Antigen-Presenting Cells in Allogeneic Hematopoietic Stem Cell Transplantation1

    OpenAIRE

    Li, Jian-Ming; Southerland, Lauren T.; Lu, Ying; Darlak, Kataryna A.; Giver, Cynthia R.; McMillin, Douglas W.; Harris, Wayne A.C.; Jaye, David L.; Waller, Edmund K.

    2009-01-01

    We investigated the roles of specific subsets of donor APCs purified from bone marrow in donor T cell activation and graft-vs-leukemia (GvL) activity in murine models of hemopoietic stem cell transplantation. Lineage−CD11c+ APC precursors were separated from donor bone marrow based on expression of CD11b. Transplanting lineage−CD11c+CD11b− APC (CD11b− APC) in combination with c-kit+Sca-1+lineage− hemopoietic stem cells (HSC) and congenic donor T cells led to increased donor CD4+ and CD8+ T ce...

  18. Pancreatic involvement in small cell lung cancer

    International Nuclear Information System (INIS)

    Few data are available concerning incidence, clinical picture, and prognosis for pancreatic metastases of small cell lung carcinoma. In this paper we review the related literature available in English language. Although pancreatic metastases are generally asymptomatic, they can rarely produce clinical symptoms or functional abnormalities. The widespread use of multi-detector computerised tomography (CT) in contemporary medical practice has led to an increased detection of pancreatic metastases in oncology patients. Tissue diagnosis is imperative because radiological techniques alone are incapable of differentiating them from primary pancreatic tumours. Pancreatic metastases occur in the relative end stage of small cell lung cancer. The main complications of these lesions, although rare, are acute pancreatitis and obstructive jaundice. Early chemotherapy can provide a survival benefit even in patients with mild acute pancreatitis or extrahepatic biliary obstruction

  19. Pancreatic involvement in small cell lung cancer

    OpenAIRE

    Gonlugur, Ugur; Mirici, Arzu; Karaayvaz, Muammer

    2014-01-01

    Background Few data are available concerning incidence, clinical picture, and prognosis for pancreatic metastases of small cell lung carcinoma. In this paper we review the related literature available in English language. Conclusions Although pancreatic metastases are generally asymptomatic, they can rarely produce clinical symptoms or functional abnormalities. The widespread use of multi-detector computerised tomography (CT) in contemporary medical practice has led to an increased detection ...

  20. HIV/AIDS患者外周血T淋巴细胞亚群的研究%Study on T cell subsets in HIV/AIDS patients

    Institute of Scientific and Technical Information of China (English)

    李海英; 曹振环; 计云霞; 吴昊; 陈新月

    2008-01-01

    Objective Analyze Naive and Mermory T cell subsets in HIV/AIDS patients and investigate their relationship with disease development. Methods T cell subsets from 15 normal control subjects, 79 HIV/AIDS patients were detected by FCM. Results With diesase progression, CD4+ Naive cell counts and ratio wasboth decreased obviously(P500组17例.外周血淋巴细胞中T细胞各亚群绝对数及百分比.结果随着疾病进展,CD4+ 初始细胞(Naive)计数和比例均逐渐减少(P0.05).结论 HIV感染者外周血T淋巴细胞亚群发生显著变化,幼稚型T淋巴细胞数目逐渐减少,功能型T淋巴细胞数目增加.本研究有助于对HIV致病机制的研究及疾病进展的监测.

  1. The beta2 integrin CD11c distinguishes a subset of cytotoxic pulmonary T cells with potent antiviral effects in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Koerner-Rettberg Cordula

    2005-07-01

    Full Text Available Abstract Background The integrin CD11c is known as a marker for dendritic cells and has recently been described on T cells following lymphotropic choriomeningitis virus infection, a systemic infection affecting a multitude of organs. Here, we characterise CD11c bearing T cells in a murine model of localised pulmonary infection with respiratory syncytial virus (RSV. Methods Mice were infected intranasally with RSV and expression of β2 integrins and T lymphocyte activation markers were monitored by flow cytometry. On day 8 post RSV infection CD11c+ CD8+ and CD11c- CD8+ T cells were assessed for cytokine production, cytotoxic activity and migration. Expression of CD11c mRNA in CD8+ T cells was assessed by quantitative PCR. Results Following RSV infection CD11c+ CD8+ T cells were detectable in the lung from day 4 onwards and accounted for 45.9 ± 4.8% of CD8+ T cells on day 8 post infection, while only few such cells were present in mediastinal lymph nodes, spleen and blood. While CD11c was virtually absent from CD8+ T cells in the absence of RSV infection, its mRNA was expressed in CD8+ T cells of both naïve and RSV infected mice. CD11c+, but not CD11c-, CD8+ T cells showed signs of recent activation, including up-regulation of CD11a and expression of CD11b and CD69 and were recruited preferentially to the lung. In addition, CD11c+ CD8+ T cells were the major subset responsible for IFNγ production, induction of target cell apoptosis in vitro and reduction of viral titres in vivo. Conclusion CD11c is a useful marker for detection and isolation of pulmonary antiviral cytotoxic T cells following RSV infection. It identifies a subset of activated, virus-specific, cytotoxic T cells that exhibit potent antiviral effects in vivo.

  2. Factoring groups into subsets

    CERN Document Server

    Szabo, Sandor

    2009-01-01

    Decomposing an abelian group into a direct sum of its subsets leads to results that can be applied to a variety of areas, such as number theory, geometry of tilings, coding theory, cryptography, graph theory, and Fourier analysis. Focusing mainly on cyclic groups, Factoring Groups into Subsets explores the factorization theory of abelian groups. The book first shows how to construct new factorizations from old ones. The authors then discuss nonperiodic and periodic factorizations, quasiperiodicity, and the factoring of periodic subsets. They also examine how tiling plays an important role in n

  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

    OpenAIRE

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

    2014-01-01

    ABSTRACT 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...

  4. Effects of spray-dried porcine plasma and plant extracts on intestinal morphology and on leukocyte cell subsets of weaned pigs.

    Science.gov (United States)

    Nofrarías, M; Manzanilla, E G; Pujols, J; Gibert, X; Majó, N; Segalés, J; Gasa, J

    2006-10-01

    We evaluated the effects of a 6% spray-dried porcine plasma (SDPP) and a plant extracts mixture (XT; 5% carvacrol, 3% cinnamaldehyde, and 2% capsicum oleoresin) on the productive performance, intestinal morphology, and leukocyte cell subsets of early-weaned pigs compared with a control group. Morphometry of the jejunum, ileum, and colon, and immune cell analysis of blood, ileocolic lymph node (LN), and ileal Peyer's patches were done in 24 weaned pigs (20 +/- 2 d) at 19 or 21 d postweaning. Although SDPP and XT treatments did not increase ADG or ADFI, SDPP improved the G:F ratio (P = 0.024) compared with the control group. Dietary SDPP reduced the percentages of blood monocytes (P = 0.006) and macrophages in ileal Peyer's patches and LN (P = 0.04), of B lymphocytes (P = 0.04) and gammadelta+ T cells in LN (P = 0.009), and of intraepithelial lymphocytes (P = 0.026) as well as the density of lamina propria cells in the colon (P < 0.01). Dietary XT reduced intraepithelial lymphocyte numbers in jejunum (P = 0.034) and the percentages of blood cytotoxic cells (P = 0.07) and B lymphocytes in LN (P = 0.03); however, XT increased blood monocytes (P = 0.038) and the density of lamina propria lymphocytes in the colon (P = 0.003). These results indicate that dietary SDPP and plant extracts can affect intestinal morphology and immune cell subsets of gut tissues and blood in weaned pigs. Furthermore, the effects of SDPP suggest lower activation of the immune system of the piglets. PMID:16971575

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

    International Nuclear Information System (INIS)

    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.)

  6. 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.

  7. Vicia villosa agglutinin separates freshly isolated Peyer's Patch T cells into interleukin 5- or interleukin 2-producing subsets

    OpenAIRE

    1989-01-01

    Murine L3T4 T cells freshly isolated from Peyer's Patch were fractionated based on differential adherence to Vicia villosa agglutinin (VVA). VVA adherent cells secreted IL-5, but not IL-2, after stimulation with Con A and IL-1. In striking contrast, VVA nonadherent PP L3T4 T cells secreted IL-2, but not IL-5, under the same conditions. In addition, supernatants from VVA adherent, but not from VVA nonadherent cells cultures, enhanced IgA secretion by LPS-stimulated splenic B cells to the same ...

  8. Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets

    OpenAIRE

    Laurent Muller; Masato Mitsuhashi; Patricia Simms; GOODING, WILLIAM E.; Whiteside, Theresa L.

    2016-01-01

    Tumor cell-derived exosomes (TEX) suppress functions of immune cells. Here, changes in the gene profiles of primary human T lymphocytes exposed in vitro to exosomes were evaluated. CD4+ Tconv, CD8+ T or CD4+ CD39+ Treg were isolated from normal donors’ peripheral blood and co-incubated with TEX or exosomes isolated from supernatants of cultured dendritic cells (DEX). Expression levels of 24–27 immune response-related genes in these T cells were quantified by qRT-PCR. In activated T cells, TEX...

  9. Unsupervised Feature Subset Selection

    DEFF Research Database (Denmark)

    Søndberg-Madsen, Nicolaj; Thomsen, C.; Pena, Jose

    This paper studies filter and hybrid filter-wrapper feature subset selection for unsupervised learning (data clustering). We constrain the search for the best feature subset by scoring the dependence of every feature on the rest of the features, conjecturing that these scores discriminate some...... irrelevant features. We report experimental results on artificial and real data for unsupervised learning of naive Bayes models. Both the filter and hybrid approaches perform satisfactorily....

  10. On best subset regression

    OpenAIRE

    Xiong, Shifeng

    2011-01-01

    In this paper we discuss the variable selection method from \\ell0-norm constrained regression, which is equivalent to the problem of finding the best subset of a fixed size. Our study focuses on two aspects, consistency and computation. We prove that the sparse estimator from such a method can retain all of the important variables asymptotically for even exponentially growing dimensionality under regularity conditions. This indicates that the best subset regression method can efficiently shri...

  11. 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.

  12. 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. PMID:27114212

  13. Identification of keratinocyte proteins that mark subsets of cells in the epidermal stratum basale: comparisons with the intestinal epithelium

    DEFF Research Database (Denmark)

    Dabelsteen, Sally; Troelsen, Jesper T; Olsen, Jorgen

    2003-01-01

    Rapid renewing epithelia such as the epidermis and the intestinal epithelium are maintained by proliferation of undifferentiated stem cells located at specific locations. Recent experiments indicate that stem cells from adult organs might be able to populate tissues other than their tissue of...... origin. Such findings open the possibility that adult stem cells from different tissues might share common markers. We investigated this by two different approaches. In a first approach we compared the expression profiles from epidermal and intestinal epithelial cells at various stages of differentiation....... We found that 108 of 1,176 genes analyzed were expressed above background in either keratinocytes or enterocytes and, among these, only 16 genes were expressed in both cell types. Of these 16 genes expressed in both cell types, only five displayed the same shift in expression level during cellular...

  14. 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.

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

    International Nuclear Information System (INIS)

    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+ 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+, but not Lyb-5- 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+ 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

  16. Murine regulatory T cells contain hyper-proliferative and death-prone subsets with differential ICOS expression

    OpenAIRE

    Chen, Yong; Shen, Shudan; Gorentla, Balachandra; Gao, Jimin; Zhong, Xiao-Ping

    2012-01-01

    Regulatory T cells (Treg) are crucial for self-tolerance. It has been an enigma that Treg exhibit an anergic phenotype reflected by hypo-proliferation in vitro following T cell receptor (TCR) stimulation but undergo vigorous proliferation in vivo. We report here that, different from conventional T cells (Tcon), murine Treg are prone to death but hyper-proliferative in vitro and in vivo. During in vitro culture, most Treg die with or without TCR stimulation, correlated with constitutive activa...

  17. Cellular interactions of human T cell subsets defined by monoclonal antibodies in regulating B cell differentiation: a comparative study in Nocardia water-soluble mitogen- and pokeweed mitogen-stimulated culture systems

    International Nuclear Information System (INIS)

    Two distinct human T cell subsets, OKT4+ cellrich and OKT8+ cellrich populations, were negatively selected with reasonable purity by C-mediated cytolysis with the use of monoclonal OKT4 and OKT8 antibodies. B cells were purified by rigorous depletion of E rosetting cells. Purified B cells responded to pokeweed mitogen (PWM) to yield a negligible number of immunoglobulin-producing cells (lg-PC), which were identified by a direct immunofluorescence method, after 7 days of culture, and to Nocardia water-soluble mitogen (NWSM) with the generation of a few, but a significant number of, lg-PC. Helper function of each T cell subset was measured as the ability of added T cells to restore the generation of lg-PC by B cells after 7 days of culture with NWSM or PWM. Results indicate that although NWSM by itself did not activate suppressor T cells to become effector cells, OKT8+ cells in the NWSM-driven system were able to exert suppressor effect for B cell differentiation only when used in combination with PWM-prestimulated OKT4+ cells. PWM-prestimulated OKT4+ cells had a pivotal role for the expression of suppressor activity by OKT8+ cells in this system, and the ability of these OKT4+ cells to interact with OKT8+ cells appeared to be radiosensitive

  18. 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.

  19. Tc17, a Unique Subset of CD8 T Cells That Can Protect against Lethal Influenza Challenge1

    OpenAIRE

    Hamada, Hiromasa; de la Luz Garcia-Hernandez, Maria; Reome, Joyce B.; Misra, Sara K.; Strutt, Tara M.; McKinstry, Kai K.; Cooper, Andrea M.; Swain, Susan L.; Dutton, Richard W.

    2009-01-01

    We show here that IL-17-secreting CD4 T (Th)17 and CD8 T (Tc)17 effector cells are found in the lung following primary challenge with influenza A and that blocking Ab to IL-17 increases weight loss and reduces survival. Tc17 effectors can be generated in vitro using naive CD8 T cells from OT-I TCR-transgenic mice. T cell numbers expand 20-fold and a majority secretes IL-17, but little IFN-γ. Many of the IL-17-secreting cells also secrete TNF and some secrete IL-2. Tc17 are negative for granzy...

  20. 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

    2016-01-01

    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. PMID:26966045

  1. 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. PMID:26966045

  2. 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.

  3. Rapid Proliferation and Differentiation of a Subset of Circulating IgM Memory B Cells to a CpG/Cytokine Stimulus In Vitro

    Science.gov (United States)

    Vásquez, Camilo; Franco, Manuel A.; Angel, Juana

    2015-01-01

    Circulating human IgM expressing memory B cells have been incompletely characterized. Here, we compared the phenotype and in vitro functional response (capacity to proliferate and differentiate to antibody secreting cells) in response to CpG and a cytokine cocktail (IL-2, IL-6, and IL-10) of sorted naïve B cells, IgM memory B cells and isotype-switched circulating memory B cells. Compared to naïve B cells, IgM memory B cells had lower integrated mean fluorescence intensity (iMFI) of BAFF-R, CD38, CD73, and IL-21R, but higher iMFI of CD95, CD11c, TLR9, PD-1, and CD122. Compared to switched memory B cells, IgM memory B cells had higher iMFI of BAFF-R, PD-1, IL-21R, TLR9, and CD122, but lower iMFI of CD38, CD95, and CD73. Four days after receiving the CpG/cytokine cocktail, higher frequencies of IgM than switched memory B cells—and these in turn greater than naïve cells—proliferated and differentiated to antibody secreting cells. At this time point, a small percentage (median of 7.6%) of stimulated IgM memory B cells changed isotype to IgG. Thus, among the heterogeneous population of human circulating IgM memory B cells a subset is capable of a rapid functional response to a CpG/cytokine stimulus in vitro. PMID:26439739

  4. 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.

  5. CD16(+) monocyte subsets are increased in large abdominal aortic aneurysms and are differentially related with circulating and cell-associated biochemical and inflammatory biomarkers.

    Science.gov (United States)

    Ghigliotti, Giorgio; Barisione, Chiara; Garibaldi, Silvano; Brunelli, Claudio; Palmieri, Daniela; Spinella, Giovanni; Pane, Bianca; Spallarossa, Paolo; Altieri, Paola; Fabbi, Patrizia; Sambuceti, Gianmario; Palombo, Domenico

    2013-01-01

    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 CD14(dim)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(+), CD14(dim)CD16(+) monocytes and monocyte CD143 expression in AAA patients, and their relationship with Ddimer, eGFR and other inflammatory parameters. Blood from 74 AAA patients and 30 healthy controls was analyzed to determine the frequency of CD14(+)CD16(+), CD14(dim)CD16(+) monocytes and the monocyte CD143 expression by means of flow-cytometry. AAA patients had expanded CD16+ subsets (CD14(+)CD16(+): 7.66 ± 0.31% vs 5.42 ± 0.27%; CD14(dim)CD16(+): 7.43 ± 0.48% vs 5.54 ± 0.38%, AAA vs controls, mean ± SE, both p D-dimer and age, and to reduced eGFR. CD14(dim)CD16(+) cells were associated to uric acid, surface CD143, and reduced count of total leukocytes and neutrophils. Within AAA patients, the two CD16(+) subsets and the monocyte CD143 expression display different relationships with D-dimer, parameters of renal function and circulating biochemical and inflammatory biomarkers. PMID:23348634

  6. Increase in a distinct pulmonary macrophage subset possessing an antigen-presenting cell phenotype and in vitro APC activity following silica exposure

    International Nuclear Information System (INIS)

    Silica inhalation results in chronic lung inflammation and fibrosis. While the role of the alveolar macrophage (AM) is considered key to the effects of silica on lung pathology, the etiology is not completely understood. Evidence suggests an increase in antigen presenting cell (APC) activity as a contributing factor to this process, as well as potential roles for both AM and interstitial macrophages (IM) in silicosis. In order to study the effects of crystalline silica on the APC activity of pulmonary macrophages, mice were exposed intranasally and changes in pulmonary macrophage populations were assessed using flow cytometry. Following intranasal instillation of silica, a significant increase in the APC activity of AM was observed, as well as a significant increase in a subset of IM expressing classic APC markers (MHC class II, CD11c). In addition, an in vitro system using bone marrow-derived macrophages (BMDM) was generated to assess the effects of silica on the APC activity of macrophages in vitro. Data using BMDM in the in vitro APC assay demonstrated a significant increase in APC activity following silica exposure, but not following exposure to saline or a control particle (TiO2). Using a combination of in vivo and in vitro experiments, the current study describes a significant increase in an interstitial macrophage subset with an APC phenotype, as well as an increase in the APC activity of both AM and BMDM, as a direct result of exposure to crystalline silica. These studies suggest a specific mechanism, macrophage subset activation, by which crystalline silica exposure results in chronic pulmonary inflammation and, eventually, fibrosis

  7. Th Subset Balance in Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    Katsuhisa Miyake

    2011-01-01

    Full Text Available Lupus nephritis, which has various histological patterns and variable clinical outcomes, is one of the most important complications of systemic lupus nephritis (SLE. This pathogenetic mechanism in each histologically different type of lupus nephritis (LN remains unclear. Although SLE is suggested to be a Th2-driven disease, elevation of both Th1 and Th2 cytokines occurs in both humans and mice, suggesting that SLE is a complex disease driven by different lymphocyte subsets with high heterogeneity of clinical manifestations and organ involvement. Recent findings in LN elucidate an essential role for the Th1, IL-17 producing T cells and Th17 cells in the development of diffuse proliferative lupus nephritis (DPLN, and Th2 cytokine in that of membranous lupus nephritis (MLN. These data support the hypothesis that individual Th1/Th2 balance is one of the critical determinants for histopathology of LN.

  8. 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

  9. 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...

  10. Response of lymphocyte subsets and cytokines to Shenyang prescription in Sprague-Dawley rats with tongue squamous cell carcinomas induced by 4NQO

    Directory of Open Access Journals (Sweden)

    He Di

    2007-03-01

    Full Text Available Abstract Background The study was designed to investigate immunocompetence in relation to cancer progression in rat and to assess the effect of the traditional Chinese anti-cancer medicine, "Shenyang" prescription, on immunity. Methods 4-Nitroquinoline-1-oxide (4NQO was administered to 80 Sprague-Dawley (SD rats via the drinking water for up to 36 weeks. Tongue squamous cell carcinoma (SCC was confirmed by pathological examination in 61 rats. "Shenyang" prescription was administered to subgroups of these rats, and blood samples were taken before and after treatment. Lymphocyte subsets were determined by flow cytometry. Serum Th1 and Th2-type cytokines were assessed by an enzyme-linked immunosorbent assay. Results As the cancer progressed at the tongue root, the percentage of CD3+CD4+ T lymphocytes and NK cells and the levels of IFN-γ and IL-2 decreased gradually, while the percentage of CD3+CD8+ T lymphocytes and the levels of IL-4 and IL-10 increased. The CD4+/CD8+ ratios were lower in the cancer groups than in the control group. However, after administering "Shenyang" prescription, the levels of CD3+CD4+ T lymphocytes, NK cells, IFN-γ and IL-2 increased, while the CD3+CD8+ T lymphocyte counts and the levels of IL-4 and IL-10 decreased. Conclusion 4NQO-induced lesions were good models for exploring oral cavity carcinogenesis. The rats with 4NQO-induced SCC demonstrated abnormalities in lymphocyte subsets and a shift from Th1-type to Th2-type, which were good models for assessing the effect of anticancer agent on immunity. Oral cancer progression was associated with an aggressive disturbance of immune function. "Shenyang" prescription has the ability to improve the disturbance of immune function.

  11. Response of lymphocyte subsets and cytokines to Shenyang prescription in Sprague-Dawley rats with tongue squamous cell carcinomas induced by 4NQO

    International Nuclear Information System (INIS)

    The study was designed to investigate immunocompetence in relation to cancer progression in rat and to assess the effect of the traditional Chinese anti-cancer medicine, 'Shenyang' prescription, on immunity. 4-Nitroquinoline-1-oxide (4NQO) was administered to 80 Sprague-Dawley (SD) rats via the drinking water for up to 36 weeks. Tongue squamous cell carcinoma (SCC) was confirmed by pathological examination in 61 rats. 'Shenyang' prescription was administered to subgroups of these rats, and blood samples were taken before and after treatment. Lymphocyte subsets were determined by flow cytometry. Serum Th1 and Th2-type cytokines were assessed by an enzyme-linked immunosorbent assay. As the cancer progressed at the tongue root, the percentage of CD3+CD4+ T lymphocytes and NK cells and the levels of IFN-γ and IL-2 decreased gradually, while the percentage of CD3+CD8+ T lymphocytes and the levels of IL-4 and IL-10 increased. The CD4+/CD8+ ratios were lower in the cancer groups than in the control group. However, after administering 'Shenyang' prescription, the levels of CD3+CD4+ T lymphocytes, NK cells, IFN-γ and IL-2 increased, while the CD3+CD8+ T lymphocyte counts and the levels of IL-4 and IL-10 decreased. 4NQO-induced lesions were good models for exploring oral cavity carcinogenesis. The rats with 4NQO-induced SCC demonstrated abnormalities in lymphocyte subsets and a shift from Th1-type to Th2-type, which were good models for assessing the effect of anticancer agent on immunity. Oral cancer progression was associated with an aggressive disturbance of immune function. 'Shenyang' prescription has the ability to improve the disturbance of immune function

  12. 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.

  13. Foxp3-deficient regulatory T cells do not revert into conventional effector CD4+ T cells but constitute a unique cell subset1

    OpenAIRE

    Kuczma, Michal; Podolsky, Robert; Garge, Nikhil; Daniely, Danielle; Pacholczyk, Rafal; Ignatowicz, Leszek; Kraj, Piotr

    2009-01-01

    Homeostasis in the immune system is maintained by specialized regulatory CD4+ T cells (Treg) expressing transcription factor Foxp3. According to the current paradigm, high affinity interactions between T cell receptors (TCRs) and class II MHC/peptide complexes in thymus “instruct” developing thymocytes to upregulate Foxp3 and become Treg cells. However, the loss or downregulation of Foxp3 does not disrupt the development of Treg cells but abrogates their suppressor function. Here we show that...

  14. 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

    OpenAIRE

    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

    2011-01-01

    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 malig...

  15. Adult Langerhans Cell Histiocytosis with Hepatic and Pulmonary Involvement

    OpenAIRE

    Bruno Araujo; Francisco Costa; Joanne Lopes; Ricardo Castro

    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 histiocyt...

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

    International Nuclear Information System (INIS)

    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

  17. 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.

  18. Study on the changes of serum leptin level, peripheral B cell number, T cell subsets distribution type in patients with hepatitis C and the relationship between the changes and liver dysfunction

    International Nuclear Information System (INIS)

    Objective: To investigate the changes of serum leptin level, B cell number, T-cell subsets in patients with hepatitis C and the relationship between the changes and liver function alterations. Methods: Serum leptin levels (with RIA), peripheral B cell number, T cell subsets distribution type (with monoclonal antibody technique), ALT and total bilirubin (with biochemistry) were measured in 65 patients with hepatitis C and 35 controls. Results: The serum leptin level and B cell percentage in the patients were significantly higher than those in controls (P<0.01), while the CD3, CD4 percentage and CD4/CD8 ratio were significantly lower (P<0.Ol). The serum leptin levels were significantly positively correlated with those of ALT and total bilirubin (P <0.01). Conclusion: Serum leptin levels correlated well with those of two major liver function indicators (ALT and total bilirubin), thus, leptin might be used as a part of liver function test battery. Changes in B and T cell subsets demonstrated immuno-disturbances in patients with hepatitis C. (authors)

  19. 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.

  20. 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

    (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...... 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......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...

  1. 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; Marcussen, N; Fisker, R; Jensen, J J; Naredi, P; Hokland, M

    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......-six patients with metastatic renal cell carcinoma were treated with low dose s.c. interleukin-2, interferon-alpha and histamine. A total of 250 blood samples and 62 core needle biopsies from 23 and 19 of these patients, respectively, were analysed. After 2 weeks of treatment, a significant positive correlation...... 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...

  2. Identification of a human HLA-E-restricted CD8+ T cell subset in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine.

    Science.gov (United States)

    Salerno-Gonçalves, Rosângela; Fernandez-Viña, Marcelo; Lewinsohn, David M; Sztein, Marcelo B

    2004-11-01

    Our previous studies in volunteers immunized with Salmonella enterica serovar Typhi (S. Typhi) have suggested an important role for CD8+ T cells in host defense. In this study we describe a novel subset of nonclassical human HLA-E-restricted S. Typhi-specific CD8+ T cells derived from PBMC of Ty21a typhoid vaccinees. CD3+CD8+CD4-CD56- T cells effectively killed S. Typhi-infected targets regardless of whether they share classical HLA class I molecules with them, by a FAS-independent, granule-dependent mechanism, as evidenced by induction of granzyme B release and the blocking effects of concanamycin and strontium ions. The expression of HLA-E Ags, but not CD1-a, -b, or -c, on the membrane of S. Typhi-infected targets rendered them susceptible to lysis. Moreover, anti-HLA-E Abs partially blocked these responses. We also demonstrated that presentation of S. Typhi Ags via HLA-E could stimulate IFN-gamma production. Increases in the net frequency of IFN-gamma spot-forming cells were observed in the presence of targets coated with peptides that contain S. Typhi GroEL HLA-E binding motifs. These results demonstrate that HLA-E binds nonamer peptides derived from bacterial proteins and trigger CD8+-mediated lysis and IFN-gamma production when exposed to infected targets, raising the possibility that this novel effector mechanism might contribute to host defense against intracellular bacterial infections. PMID:15494539

  3. Changes in Leukocyte Subsets And Anti-dsDNA Antibody Levels After B Cell Depletion Therapy in Systemic Lupus Erythematosus

    OpenAIRE

    Lazarus, M. N.

    2015-01-01

    Clinical response to B cell depletion therapy (BCDT) is highly variable in patients with systemic lupus erythematosus (SLE). Reductions in anti-dsDNA antibody levels also vary. It has been shown that early relapse is more likely if anti-dsDNA antibody levels remain high after BCDT. The cellular factors that determine how anti-dsDNA antibodies are produced and whether they are likely to fall after BCDT have not been clarified. This thesis describes two different immunological processes that mi...

  4. A reassessment of IgM memory subsets in humans

    Science.gov (United States)

    Bagnara, Davide; Squillario, Margherita; Kipling, David; Mora, Thierry; Walczak, Aleksandra M.; Da Silva, Lucie; Weller, Sandra; Dunn-Walters, Deborah K.; Weill, Jean-Claude; Reynaud, Claude-Agnès

    2015-01-01

    From paired blood and spleen samples from three adult donors we performed high-throughput V-h sequencing of human B-cell subsets defined by IgD and CD27 expression: IgD+CD27+ (“MZ”), IgD−CD27+(“memory”, including IgM (“IgM-only”), IgG and IgA) and IgD−CD27− cells (“double-negative”, including IgM, IgG and IgA). 91,294 unique sequences clustered in 42,670 clones, revealing major clonal expansions in each of these subsets. Among these clones, we further analyzed those shared sequences from different subsets or tissues for Vh-gene mutation, H-CDR3-length, and Vh/Jh usage, comparing these different characteristics with all sequences from their subset of origin, for which these parameters constitute a distinct signature. The IgM-only repertoire profile differed notably from that of MZ B cells by a higher mutation frequency, and lower Vh4 and higher Jh6 gene usage. Strikingly, IgM sequences from clones shared between the MZ and the memory IgG/IgA compartments showed a mutation and repertoire profile of IgM-only and not of MZ B cells. Similarly, all IgM clonal relationships (between MZ, IgM-only, and double-negative compartments) involved sequences with the characteristics of IgM-only B cells. Finally, clonal relationships between tissues suggested distinct recirculation characteristics between MZ and switched B cells. The “IgM-only” subset (including cells with its repertoire signature but higher IgD or lower CD27 expression levels) thus appear as the only subset showing precursor-product relationships with CD27+ switched memory B cells, indicating that they represent germinal center-derived IgM memory B cells, and that IgM memory and MZ B cells constitute two distinct entities. PMID:26355154

  5. Functional characterization of human Cd33+ And Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines

    Directory of Open Access Journals (Sweden)

    Arger Nicholas

    2011-06-01

    Full Text Available Abstract Background Tumor immune tolerance can derive from the recruitment of suppressor cell populations, including myeloid-derived suppressor cells (MDSC. In cancer patients, MDSC accumulation correlates with increased tumor burden, but the mechanisms of MDSC induction remain poorly understood. Methods This study examined the ability of human tumor cell lines to induce MDSC from healthy donor PBMC using in vitro co-culture methods. These human MDSC were then characterized for morphology, phenotype, gene expression, and function. Results Of over 100 tumor cell lines examined, 45 generated canonical CD33+HLA-DRlowLineage- MDSC, with high frequency of induction by cervical, ovarian, colorectal, renal cell, and head and neck carcinoma cell lines. CD33+ MDSC could be induced by cancer cell lines from all tumor types with the notable exception of those derived from breast cancer (0/9, regardless of hormone and HER2 status. Upon further examination, these and others with infrequent CD33+ MDSC generation were found to induce a second subset characterized as CD11b+CD33lowHLA-DRlowLineage-. Gene and protein expression, antibody neutralization, and cytokine-induction studies determined that the induction of CD33+ MDSC depended upon over-expression of IL-1β, IL-6, TNFα, VEGF, and GM-CSF, while CD11b+ MDSC induction correlated with over-expression of FLT3L and TGFβ. Morphologically, both CD33+ and CD11b+ MDSC subsets appeared as immature myeloid cells and had significantly up-regulated expression of iNOS, NADPH oxidase, and arginase-1 genes. Furthermore, increased expression of transcription factors HIF1α, STAT3, and C/EBPβ distinguished MDSC from normal counterparts. Conclusions These studies demonstrate the universal nature of MDSC induction by human solid tumors and characterize two distinct MDSC subsets: CD33+HLA-DRlowHIF1α+/STAT3+ and CD11b+HLA-DRlowC/EBPβ+, which should enable the development of novel diagnostic and therapeutic reagents for

  6. A combination HIV reporter virus system for measuring post-entry event efficiency and viral outcome in primary CD4+ T cell subsets.

    Science.gov (United States)

    Tilton, Carisa A; Tabler, Caroline O; Lucera, Mark B; Marek, Samantha L; Haqqani, Aiman A; Tilton, John C

    2014-01-01

    Fusion between the viral membrane of human immunodeficiency virus (HIV) and the host cell marks the end of the HIV entry process and the beginning of a series of post-entry events including uncoating, reverse transcription, integration, and viral gene expression. The efficiency of post-entry events can be modulated by cellular factors including viral restriction factors and can lead to several distinct outcomes: productive, latent, or abortive infection. Understanding host and viral proteins impacting post-entry event efficiency and viral outcome is critical for strategies to reduce HIV infectivity and to optimize transduction of HIV-based gene therapy vectors. Here, we report a combination reporter virus system measuring both membrane fusion and viral promoter-driven gene expression. This system enables precise determination of unstimulated primary CD4+ T cell subsets targeted by HIV, the efficiency of post-entry viral events, and viral outcome and is compatible with high-throughput screening and cell-sorting methods. PMID:24025341

  7. Remodeling of B-Cell Subsets in Blood during Pegylated IFNα-2a Therapy in Patients with Chronic Hepatitis B Infection

    Science.gov (United States)

    Jacob, Marie-Christine; Dufeu-Duchesne, Tania; Bertucci, Inga; Pouget, Noelle; Brevot-Lutton, Ophelie; Zoulim, Fabien; Bourliere, Marc; Plumas, Joel; Leroy, Vincent

    2016-01-01

    The ultimate goal of pegylated interferon-alfa-2a (Peg-IFN-α) therapy in chronic hepatitis B (CHB) infection is HBsAg seroconversion. Even though B cells are major mediators of a positive clinical outcome, their modulation during Peg-IFN-α therapy has not yet been described. We investigated here the effects of Peg-IFN-α on eight circulating B-cell subsets thanks to an original multi-gating approach based on CD19, CD27, IgD, CD10, and CD38 markers in patients with CHB treated with nucleos(t)ide analog alone or in combination with Peg-IFN-α. These dynamic changes were analyzed during the 48-weeks of Peg-IFN-α therapy and up to 2 years after the cessation of treatment. The CD19+CD27-IgD+CD10+CD38high transitional B cells and the CD19+CD27+IgD-CD10-CD38high plasmablasts continuously increased, whereas the CD19+CD27-IgD+CD10-CD38low naive, CD19+CD27+IgD+ natural memory, and CD19+CD27+IgD-CD10-CD38low post-germinal center B cells decreased during the course of Peg-IFNα treatment. Such modulations correlated with a sustained increase in sCD30 levels and the decrease in plasma HBsAg. However, no seroconversion occurred and all parameters returned to baseline after the stop of the treatment. Peg-IFN-α therapy mediates a remodeling of B-cell compartmentalization, without clinical relevance. Our study provides new insights into the immunomodulatory effects of Peg-IFN-α on circulating B-cells, and questioned the benefit of the add-on Peg-IFN-α treatment in CHB. PMID:27281019

  8. Remodeling of B-Cell Subsets in Blood during Pegylated IFNα-2a Therapy in Patients with Chronic Hepatitis B Infection.

    Science.gov (United States)

    Aspord, Caroline; Bruder Costa, Juliana; Jacob, Marie-Christine; Dufeu-Duchesne, Tania; Bertucci, Inga; Pouget, Noelle; Brevot-Lutton, Ophelie; Zoulim, Fabien; Bourliere, Marc; Plumas, Joel; Leroy, Vincent

    2016-01-01

    The ultimate goal of pegylated interferon-alfa-2a (Peg-IFN-α) therapy in chronic hepatitis B (CHB) infection is HBsAg seroconversion. Even though B cells are major mediators of a positive clinical outcome, their modulation during Peg-IFN-α therapy has not yet been described. We investigated here the effects of Peg-IFN-α on eight circulating B-cell subsets thanks to an original multi-gating approach based on CD19, CD27, IgD, CD10, and CD38 markers in patients with CHB treated with nucleos(t)ide analog alone or in combination with Peg-IFN-α. These dynamic changes were analyzed during the 48-weeks of Peg-IFN-α therapy and up to 2 years after the cessation of treatment. The CD19+CD27-IgD+CD10+CD38high transitional B cells and the CD19+CD27+IgD-CD10-CD38high plasmablasts continuously increased, whereas the CD19+CD27-IgD+CD10-CD38low naive, CD19+CD27+IgD+ natural memory, and CD19+CD27+IgD-CD10-CD38low post-germinal center B cells decreased during the course of Peg-IFNα treatment. Such modulations correlated with a sustained increase in sCD30 levels and the decrease in plasma HBsAg. However, no seroconversion occurred and all parameters returned to baseline after the stop of the treatment. Peg-IFN-α therapy mediates a remodeling of B-cell compartmentalization, without clinical relevance. Our study provides new insights into the immunomodulatory effects of Peg-IFN-α on circulating B-cells, and questioned the benefit of the add-on Peg-IFN-α treatment in CHB. PMID:27281019

  9. IGF1R Derived PI3K/AKT Signaling Maintains Growth in a Subset of Human T-Cell Acute Lymphoblastic Leukemias.

    Science.gov (United States)

    Gusscott, Samuel; Jenkins, Catherine E; Lam, Sonya H; Giambra, Vincenzo; Pollak, Michael; Weng, Andrew P

    2016-01-01

    Insulin-like growth factor 1 receptor (IGF1R) is a prevalent signaling pathway in human cancer that supports cell growth/survival and thus contributes to aggressive biological behavior. Much work has gone into development of IGF1R inhibitors; however, candidate agents including small molecule tyrosine kinase inhibitors and blocking antibodies have yet to fulfill their promise clinically. Understanding cellular features that define sensitivity versus resistance are important for effective patient selection and anticipation of outgrowth of a resistant clone. We previously identified an important role for IGF signaling in T-cell acute lymphoblastic leukemia (T-ALL) relying primarily upon genetically defined mouse models. We present here an assessment of IGF1R dependence in human T-ALL using a broad panel of 27 established cell lines that capture a spectrum of the genetic variation that might be encountered in clinical practice. We observed that a subset of cell lines are sensitive to IGF1R inhibition and are characterized by high levels of surface IGF1R expression and PTEN positivity. Interestingly, lentiviral expression or knock-down of PTEN in PTEN-negative/positive cell lines, respectively, had limited effects on their response to IGF1R inhibition, suggesting that PTEN contributes to, but does not define IGF dependence. Additionally, we characterize downstream PI3K/AKT signaling as dominant over RAS/RAF/MEK/ERK in mediating growth and/or survival in this context. Finally, we demonstrate that IGF and interleukin-7 (IL-7) fulfill non-overlapping roles in supporting T-ALL growth. These findings are significant in that they reveal cellular features and downstream mechanisms that may determine the response of an individual patient's tumor to IGF1R inhibitor therapy. PMID:27532210

  10. Sirtuin 1 is upregulated in a subset of hepatocellular carcinomas where it is essential for telomere maintenance and tumor cell growth.

    Science.gov (United States)

    Chen, Juan; Zhang, Bin; Wong, Nathalie; Lo, Anthony W I; To, Ka-Fai; Chan, Anthony W H; Ng, Margaret H L; Ho, Cecilia Y S; Cheng, Suk-Hang; Lai, Paul B S; Yu, Jun; Ng, Ho-Keung; Ling, Ming-Tat; Huang, Ai-Long; Cai, Xue-Fei; Ko, Ben C B

    2011-06-15

    Hepatocellular carcinoma (HCC) is a highly malignant tumor with a poor prognosis. Treatment of HCC is complicated by the fact that the disease is often diagnosed at an advanced stage when it is no longer amenable to curative surgery, and current systemic chemotherapeutics are mostly inefficacious. Sirtuin 1 (SIRT1) is a class III histone deacetylase that is implicated in gene regulations and stress resistance. In this study, we found that SIRT1 is essential for the tumorigenesis of HCC. We showed that although SIRT1 was expressed at very low levels in normal livers, it was overexpressed in HCC cell lines and in a subset of HCC. Tissue microarray analysis of HCC and adjacent nontumoral liver tissues revealed a positive correlation between the expression levels of SIRT1 and advancement in tumor grades. Downregulation of SIRT1 consistently suppressed the proliferation of HCC cells via the induction of cellular senescence or apoptosis. SIRT1 silencing also caused telomere dysfunction-induced foci and nuclear abnormality that were clearly associated with reduced expressions of telomerase reverse transcriptase (TERT), and PTOP, which is a member of the shelter in complex. Ectopic expression of either TERT or PTOP in SIRT1-depleted cells significantly restored cell proliferation. There was also a positive correlation between the level of induction of SIRT1 and TERT [corrected] in human HCC. Finally, SIRT1-silencing sensitized HCC cells to doxorubicin treatment. Together, our findings reveal a novel function for SIRT1 in telomere maintenance of HCC, and they rationalize the clinical exploration of SIRT1 inhibitors for HCC therapy. PMID:21527554

  11. 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.

  12. Concomitant nodal involvement by Langerhans cell histiocytosis and Hodgkin's lymphoma.

    Science.gov (United States)

    Geurten, Claire; Thiry, Albert; Jamblin, Paul; Demarche, Martine; Hoyoux, Claire

    2015-12-01

    A 10-year-old girl with a family history of Hodgkin's lymphoma presented with a 2 month history of cervical lymphadenopathy and weight loss. Biopsy indicated concomitant nodal involvement by Langerhans cell histiocytosis and Hodgkin's lymphoma. Such an association is rare, especially so in children, but is not an isolated phenomenon, thereby prompting the question of whether Langerhans cell histiocytosis is a reactive or a neoplastic process. PMID:26556799

  13. KIR2DL4 copy number variation is associated with CD4+ T-cell depletion and function of cytokine-producing NK cell subsets in SIV-infected Mamu-A*01-negative rhesus macaques.

    Science.gov (United States)

    Hellmann, Ina; Letvin, Norman L; Schmitz, Jörn E

    2013-05-01

    Here, we demonstrate that KIR2DL4 copy number variation (CNV) is associated with CD4(+) T-cell decline and functionality of cytokine-producing NK cells during primary simian immunodeficiency virus (SIV) infection in Mamu-A*01(-) Indian-origin rhesus macaques, with higher KIR2DL4 copy numbers being associated with a better preservation of CD4(+) T cells and an increased gamma interferon (IFN-γ) production from stimulated cytokine-producing NK cell subsets during acute SIVmac251 infection. These findings underscore the crucial role of activating killer-cell immunoglobulin-like receptors (KIRs) in NK cell-mediated SIV responses during early SIV infection. PMID:23449795

  14. 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.

  15. 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

  16. 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......” compartments in the human cell - where most cellular energy is produced. The findings may ultimately explain the cause of certain diseases with relation to the mitochondria.......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...

  17. 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.

  18. Langerhans' cell histiocytosis: pathology, imaging and treatment of skeletal involvement

    International Nuclear Information System (INIS)

    Langerhans' cell histiocytosis (LCH) is manifested in a variety of ways, the most common being the eosinophilic granuloma, a localized, often solitary bone lesion that occurs predominantly in the pediatric age group. The hallmark of LCH is the proliferation and accumulation of a specific histiocyte: the Langerhans' cell. In bone this may cause pain and adjacent soft-tissue swelling, but some lesions are asymptomatic. LCH can involve any bone, but most lesions occur in the skull (especially the calvarium and temporal bones), the pelvis, spine, mandible, ribs, and tubular bones. Imaging diagnosis of the disease in bone is first based on the plain radiographic appearance, which is usually a central destructive, aggressive-looking lesion. In the skull, the lesions develop in the diploic space, are lytic, and their edges may be beveled, scalloped or confluent (geographic), or show a ''button sequestrum.'' Vertebral body involvement usually causes collapse, resulting in vertebra plana. With significant recent improvements in the quality of gamma cameras, imaging techniques, and in studying children, bone scintigraphy at diagnosis and on follow-up usually reveals the sites of active disease, especially when the involvement is polyostotic. CT and MR imaging are very useful in providing detailed cross-sectional anatomic detail of the involved bone, including the bone marrow and the adjacent soft tissues. CT is better suited for demonstrating bone detail and MR imaging for bone marrow and soft-tissue involvement. (orig.)

  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. Prediction based on mean subset

    DEFF Research Database (Denmark)

    Øjelund, Henrik; Brown, P. J.; Madsen, Henrik;

    2002-01-01

    the coefficient vectors from each subset should be weighted. It is not computationally feasible to calculate the mean subset coefficient vector for larger problems, and thus we suggest an algorithm to find an approximation to the mean subset coefficient vector. In a comprehensive Monte Carlo simulation study...

  1. 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

  2. Expansion of CD8+ T cells lacking Sema4D/CD100 during HIV-1 infection identifies a subset of T cells with decreased functional capacity

    OpenAIRE

    Eriksson, Emily M.; Milush, Jeffrey M.; Ho, Emily L.; Batista, Mariana D.; Holditch, Sara J.; Keh, Chris E.; Norris, Philip J.; Keating, Sheila M.; Deeks, Steven G; Hunt, Peter W.; Martin, Jeffrey N.; Rosenberg, Michael G.; Hecht, Frederick M.; Nixon, Douglas F.

    2012-01-01

    Sema4D, also known as CD100, is a constitutively expressed immune semaphorin on T cells and NK cells. CD100 has important immune regulatory functions that improve antigen-specific priming by antigen-presenting cells, and can also act as a costimulatory molecule on T cells. We investigated the consequence of HIV-1 infection on CD100 expression by T cells, and whether CD100 expression signifies functionally competent effector cells. CD100 expression on T cells from healthy individuals was compa...

  3. Extra-osseous involvement of Langerhans' cell histiocytosis in children

    International Nuclear Information System (INIS)

    The predominant clinical and radiological features of Langerhans' cell histiocytosis (LCH) in children are due to osseous involvement. Extra-osseous disease is far less common, occurring in association with bone disease or in isolation; nearly all anatomical sites may be affected and in very various combinations. The following article is based on a multicentre review of 31 children with extra-osseous LCH. The objective is to summarise the diverse possibilities of organ involvement. The radiological manifestations using different imaging modalities are rarely pathognomonic on their own. Nevertheless, familiarity with the imaging findings, especially in children with systemic disease, may be essential for early diagnosis. (orig.)

  4. Substrates of protein kinases involved in cell signal transduction

    International Nuclear Information System (INIS)

    In this study substrates for protein-tyrosine kinases and protein kinase C are examined to gain a better understanding of the conditions of their phosphorylation, their functions, and their potential involvement in intracellular signaling pathways. The tissue, cell type, and intracellular distributions of two protein-tyrosine kinase substrates, termed p36 and p81, are determined by immunoblotting of murine tissues, indirect immunofluorescence and immunoperoxidase staining of frozen rat tissue sections, and biochemical fractionation and indirect immunofluorescence staining of tissue culture cells. Both p36 and p81 are constitutively phosphorylated to low levels in tissue culture cells. In 32P-labeled A431 cells, pp81 contains both phosphoserine and phosphothreonine. Following brief epidermal growth factor treatment of A431 cells, pp81 is more heavily phosphorylated on threonine and approximately 10% of p81 molecules become phosphorylated on tyrosine. Treatment of A431 cells with the potent tumor promoter and protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA), does not alter the phosphorylation state of p81. However, TPA treatment of A431 cells and certain other cell types leads to augmented serine phosphorylation of p36

  5. CD4CD8αα lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease.

    Science.gov (United States)

    Sarrabayrouse, Guillaume; Bossard, Céline; Chauvin, Joe-Marc; Jarry, Anne; Meurette, Guillaume; Quévrain, Elodie; Bridonneau, Chantal; Preisser, Laurence; Asehnoune, Karim; Labarrière, Nathalie; Altare, Frédéric; Sokol, Harry; Jotereau, Francine

    2014-04-01

    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 and the

  6. 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.

  7. Cerebellar and basal ganglion involvement in Langerhans cell histiocytosis

    International Nuclear Information System (INIS)

    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.)

  8. Unusual cutaneous Langerhans cell sarcoma without extracutaneous involvement

    Directory of Open Access Journals (Sweden)

    Li Yang

    2013-02-01

    Full Text Available Abstract Langerhans cell sarcoma (LCS typically presents as cytologic atypia and clinical aggressiveness and may involve multiple organs during the progression of the disease. Primary skin LCS without any extra-cutaneous site association is extremely rare and only a few such cases have been described in the literature. We present a case of unusual primary LCS in skin occurring in a middle-aged male patient. Physical examination revealed a large ulcerated cutaneous lesion and a smaller nodular lesion were located in the skin of the extensor side of his right knee. There was no regional lymph node or any other extra-cutaneous organ involvement. Histologically, typical large and pleomorphological tumor cells with epithelioid appearance and significantly malignant cytological features were observed to infiltrate in dermis and subcutaneous tissue. By immunohistochemistry, the tumor cells were positive for CD1a, S-100 protein and largerin strongly and diffusely. However, these cells were negative for CD3, CD20, CD21, pan-cytokeratin, HMB-45, Melan-A, and MPO. A diagnosis of primary cutaneous LCS was made. The patient received systemic chemotherapy of CHOP regimen, and was on a regular follow-up period for 12 months. There was no sign of relapse of tumor or any other extra-cutaneous organ involvement by whole body positron emission tomography/computed tomography (PET/CT study. Because LCS is a high-grade malignancy with poor prognosis, it suggests that strict histological analysis and thorough radiographic examination are necessary for accurately diagnosing this tumor even if cutaneous involvement presented only. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/6527428618381393

  9. Ionizing irradiation not only inactivates clonogenic potential in primary normal human diploid lens epithelial cells but also stimulates cell proliferation in a subset of this population.

    Directory of Open Access Journals (Sweden)

    Yuki Fujimichi

    Full Text Available Over the past century, ionizing radiation has been known to induce cataracts in the crystalline lens of the eye, but its mechanistic underpinnings remain incompletely understood. This study is the first to report the clonogenic survival of irradiated primary normal human lens epithelial cells and stimulation of its proliferation. Here we used two primary normal human cell strains: HLEC1 lens epithelial cells and WI-38 lung fibroblasts. Both strains were diploid, and a replicative lifespan was shorter in HLEC1 cells. The colony formation assay demonstrated that the clonogenic survival of both strains decreases similarly with increasing doses of X-rays. A difference in the survival between two strains was actually insignificant, although HLEC1 cells had the lower plating efficiency. This indicates that the same dose inactivates the same fraction of clonogenic cells in both strains. Intriguingly, irradiation enlarged the size of clonogenic colonies arising from HLEC1 cells in marked contrast to those from WI-38 cells. Such enhanced proliferation of clonogenic HLEC1 cells was significant at ≥2 Gy, and manifested as increments of ≤2.6 population doublings besides sham-irradiated controls. These results suggest that irradiation of HLEC1 cells not only inactivates clonogenic potential but also stimulates proliferation of surviving uniactivated clonogenic cells. Given that the lens is a closed system, the stimulated proliferation of lens epithelial cells may not be a homeostatic mechanism to compensate for their cell loss, but rather should be regarded as abnormal. This is because these findings are consistent with the early in vivo evidence documenting that irradiation induces excessive proliferation of rabbit lens epithelial cells and that suppression of lens epithelial cell divisions inhibits radiation cataractogenesis in frogs and rats. Thus, our in vitro model will be useful to evaluate the excessive proliferation of primary normal human lens

  10. CD16+ Monocyte Subsets Are Increased in Large Abdominal Aortic Aneurysms and Are Differentially Related with Circulating and Cell-Associated Biochemical and Inflammatory Biomarkers

    Science.gov (United States)

    Ghigliotti, Giorgio; Barisione, Chiara; Garibaldi, Silvano; Brunelli, Claudio; Palmieri, Daniela; Spinella, Giovanni; Pane, Bianca; Spallarossa, Paolo; Altieri, Paola; Fabbi, Patrizia; Sambuceti, Gianmario; Palombo, Domenico

    2013-01-01

    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 pD-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. PMID:23348634

  11. Ionizing Irradiation Not Only Inactivates Clonogenic Potential in Primary Normal Human Diploid Lens Epithelial Cells but Also Stimulates Cell Proliferation in a Subset of This Population

    OpenAIRE

    Fujimichi, Yuki; Hamada, Nobuyuki

    2014-01-01

    Over the past century, ionizing radiation has been known to induce cataracts in the crystalline lens of the eye, but its mechanistic underpinnings remain incompletely understood. This study is the first to report the clonogenic survival of irradiated primary normal human lens epithelial cells and stimulation of its proliferation. Here we used two primary normal human cell strains: HLEC1 lens epithelial cells and WI-38 lung fibroblasts. Both strains were diploid, and a replicative lifespan was...

  12. Defining origins of malignant B cells: a new circulating normal human IgM(+)D(+) B-cell subset lacking CD27 expression and displaying somatically mutated IGHV genes as a relevant memory population.

    Science.gov (United States)

    Weston-Bell, N; Townsend, M; Di Genova, G; Forconi, F; Sahota, S S

    2009-11-01

    In probing the cell of origin in malignant B cells, an imprint of somatic hypermutation (SHM) in immunoglobulin (Ig) variable (V) region genes delineates antigen encounter, and identifying the precise pathway generating SHM in the normal B-cell counterpart becomes relevant. SHM remains the definitive memory imprint in normal human B cells, but CD27 expression also delineates memory. Recently, dye extrusion adenosine triphosphate-binding transporter assays identified circulating isotype-switched memory B cells that lacked CD27, yet exhibited low levels of SHM. To extend findings, we report a pre-switched CD27(-ve) circulating memory B-cell population in normal blood using comparable assays, and isolated CD19(+)IgM(+)D(+)CD27(-ve) cells (>99% purity) for the analysis of IGHV5/IGHV3-IGHM transcripts. Of these (n=334), approximately 78% were germ line and naive B cell derived. Strikingly, 21.9% of the transcripts were mutated. They showed 3-5 mutations (13.5% of sequences) and >5 mutations (8.4% of sequences) per transcript. Accrual of mutations in a subset of CD19(+)IgM(+)D(+)CD27(-ve) cells define a new circulating pre-switched memory B-cell pool, present in substantial numbers in the population harboring naive B cells. These CD19(+)IgM(+)D(+)CD27(-ve) memory B cells may have a distinct lineage and function, and seem relevant to understanding origins of malignant B cells, in particular those of hairy cell leukemia cells, which display mutated V genes yet lack CD27 expression. PMID:19776762

  13. Cell death is involved in sexual dimorphism during preimplantation development.

    Science.gov (United States)

    Oliveira, C S; Saraiva, N Z; Lima, M R de; Oliveira, L Z; Serapião, R V; Garcia, J M; Borges, C A V; Camargo, L S A

    2016-02-01

    In bovine preimplantation development, female embryos progress at lower rates and originate smaller blastocysts than male counterparts. Although sex-specific gene expression patterns are reported, when and how sex dimorphism is established is not clear. Differences among female and male early development can be useful for human assisted reproductive medicine, when X-linked disorders risk is detected, and for genetic breeding programs, especially in dairy cattle, which requires female animals for milk production. The aim of this study was to characterize the development of female and male embryos, attempting to identify sex effects during preimplantation development and the role of cell death in this process. Using sex-sorted semen from three different bulls for fertilization, we compared kinetics of bovine sex-specific embryos in six time points, and cell death was assessed in viable embryos. For kinetics analysis, we detected an increased population of female embryos arrested at 48 and 120h.p.i., suggesting this time points as delicate stages of development for female embryos that should be considered for testing improvement strategies for assisted reproductive technologies. Assessing viable embryos quality, we found 144h.p.i. is the first time point when viable embryos are phenotypically distinct: cell number is decreased, and apoptosis and cell fragmentation are increased in female embryos at this stage. These new results lead us to propose that sex dimorphism in viable embryos is established during morula-blastocyst transition, and cell death is involved in this process. PMID:26752320

  14. 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.

  15. Subset sum phase transitions and data compression

    CERN Document Server

    Merhav, Neri

    2011-01-01

    We propose a rigorous analysis approach for the subset sum problem in the context of lossless data compression, where the phase transition of the subset sum problem is directly related to the passage between ambiguous and non-ambiguous decompression, for a compression scheme that is based on specifying the sequence composition. The proposed analysis lends itself to straightforward extensions in several directions of interest, including non-binary alphabets, incorporation of side information at the decoder (Slepian-Wolf coding), and coding schemes based on multiple subset sums. It is also demonstrated that the proposed technique can be used to analyze the critical behavior in a more involved situation where the sequence composition is not specified by the encoder.

  16. Subset sums in abelian groups

    OpenAIRE

    Balandraud, Eric; Girard, Benjamin; Griffiths, Simon; Hamidoune, Yahya Ould

    2011-01-01

    Denoting by Sigma(S) the set of subset sums of a subset S of a finite abelian group G, we prove that |Sigma(S)| >= |S|(|S|+2)/4-1 whenever S is symmetric, |G| is odd and Sigma(S) is aperiodic. Up to an additive constant of 2 this result is best possible, and we obtain the stronger (exact best possible) bound in almost all cases. We prove similar results in the case |G| is even. Our proof requires us to extend a theorem of Olson on the number of subset sums of anti-symmetric subsets S from the...

  17. 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

  18. Phagocytosis in Teleosts. Implications of the New Cells Involved

    Directory of Open Access Journals (Sweden)

    María Ángeles Esteban

    2015-12-01

    Full Text Available Phagocytosis is the process by which cells engulf some solid particles to form internal vesicles known as phagosomes. Phagocytosis is in fact a specific form of endocytosis involving the vesicular interiorization of particles. Phagocytosis is essentially a defensive reaction against infection and invasion of the body by foreign substances and, in the immune system, phagocytosis is a major mechanism used to remove pathogens and/or cell debris. For these reasons, phagocytosis in vertebrates has been recognized as a critical component of the innate and adaptive immune responses to pathogens. Furthermore, more recent studies have revealed that phagocytosis is also crucial for tissue homeostasis and remodeling. Professional phagocytes in teleosts are monocyte/macrophages, granulocytes and dendritic cells. Nevertheless, in recent years phagocytic properties have also been attributed to teleost lymphocytes and thrombocytes. The possible implications of such cells on this important biological process, new factors affecting phagocytosis, evasion of phagocytosis or new forms of phagocytosis will be considered and discussed.

  19. A subset of group A-like var genes encodes the malaria parasite ligands for binding to human brain endothelial cells

    DEFF Research Database (Denmark)

    Claessens, Antoine; Adams, Yvonne; Ghumra, Ashfaq;

    2012-01-01

    Cerebral malaria is the most deadly manifestation of infection with Plasmodium falciparum. The pathology of cerebral malaria is characterized by the accumulation of infected erythrocytes (IEs) in the microvasculature of the brain caused by parasite adhesins on the surface of IEs binding to human...... receptors on microvascular endothelial cells. The parasite and host molecules involved in this interaction are unknown. We selected three P. falciparum strains (HB3, 3D7, and IT/FCR3) for binding to a human brain endothelial cell line (HBEC-5i). The whole transcriptome of isogenic pairs of selected and.......029) but not by antibodies from controls with uncomplicated malaria (Mann-Whitney test, P = 0.58). This work describes a binding phenotype for virulence-associated group A P. falciparum erythrocyte membrane protein 1 variants and identifies targets for interventions to treat or prevent cerebral malaria....

  20. Mechanisms involved in alternariol-induced cell cycle arrest

    International Nuclear Information System (INIS)

    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 μM almost completely blocked cell proliferation. Within 30 min treatment, AOH (30 μM) 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 μM 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. 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.

  2. 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.

  3. Are testicular mast cells involved in the regulation of germ cells in man?

    Science.gov (United States)

    Windschüttl, S; Nettersheim, D; Schlatt, S; Huber, A; Welter, H; Schwarzer, J U; Köhn, F M; Schorle, H; Mayerhofer, A

    2014-07-01

    Protease activated receptor-2 (PAR-2) is the receptor for the prototype mast cell product tryptase. PAR-2 expression by cells of the human germinal epithelium was reported, but the exact cellular sites of testicular expression remained unknown. That became of interest, because mast cells, expressing tryptase, were found in the walls of seminiferous tubules of patients suffering from sub- and infertility. This location suggested that mast cells via tryptase might be able to influence PAR-2-expressing cells in the germinal epithelium. To explore these points, we used testicular paraffin-embedded sections for immunohistochemistry. PAR-2-positive cells were mostly basally located cells of the seminiferous epithelium, namely spermatogonia. Some stained for the receptor for GDNF (GFRalpha-1), and possibly represent spermatogonial stem cells (SSCs). As true human SSCs could not be examined, we turned to TCam-2 seminoma cells, expressing PAR-2 and stem cell markers, including GFRalpha-1. TCam-2 cells robustly responded to stimulation with a specific PAR-2 agonist (SLIGKV) by increased intracellular Ca(2+) levels. Recombinant tryptase and trypsin, but not a control peptide (VKGILS) evoked this response, implying functional PAR-2. Video imaging and caspase 3/7 assays showed that SLIGKV and tryptase prevented spontaneous apoptosis and increased proliferation of TCam-2 cells. The expression of the marker of pluripotency OCT3/4 was unchanged upon activation of PAR-2, suggesting that the stem cell-like character is not changed. Furthermore, human germ cell cancers were examined. A subset of seminoma and carcinoma in situ samples expressed PAR-2, indicating that yet unknown subgroups exist. Collectively, the descriptive data obtained in human testicular sections, in germ cell cancers and the functional results in TCam-2 cells imply a trophic role of mast cell-derived tryptase for human germ cells. This may be relevant for subtypes of human germ cell cancers, and possibly SSCs. It

  4. 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 colitis......) activity, reflecting retinoic acid synthesis, in UC colon, both in active disease and remission, were reduced compared to controls and inflamed Crohn’s colon. In contrast, no difference in the frequency of ALDH+ cells among blood precursors was detected between UC patients and non-inflamed controls. This...

  5. Enhanced Inducible Costimulator Ligand (ICOS-L) Expression on Dendritic Cells in Interleukin-10 Deficiency and Its Impact on T-Cell Subsets in Respiratory Tract Infection

    OpenAIRE

    Gao, Xiaoling; Zhao, Lei; Wang, Shuhe; Yang, Jie; Yang, Xi

    2013-01-01

    An association between inducible costimulator ligand (ICOS-L) expression and interleukin (IL)-10 production by dendritic cells (DCs) has been commonly found in infectious disease. DCs with higher ICOS-L expression and IL-10 production are reportedly more efficient in inducing regulatory T cells (Tregs). Here we use the Chlamydia muridarum (Cm) lung infection model in IL-10 knockout (KO) mice to test the relationship between IL-10 production and ICOS-L expression by DCs. We examined ICOS-L exp...

  6. 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.

  7. In Vivo 5FU-Exposed Human Medullary Thyroid Carcinoma Cells Contain a Chemoresistant CD133+Tumor-Initiating Cell Subset

    Czech Academy of Sciences Publication Activity Database

    Kučerová, L.; Feketeová, L.; Kozovská, Z.; Poturnajová, M.; Matusková, M.; Nencka, Radim; Babál, P.

    2014-01-01

    Roč. 24, č. 3 (2014), s. 520-532. ISSN 1050-7256 Institutional support: RVO:61388963 Keywords : cancer stem cells * thymidylate synthase * colorectal cancer Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.493, year: 2014

  8. A subset of human pancreatic beta cells express functional CD14 receptors: a signaling pathway fot beta cell-related glycolipids, sulfatide and beta-galactosylceramide

    Czech Academy of Sciences Publication Activity Database

    Osterbye, T.; Funda, David; Fundová, Petra; Mansson, J.-E.; Tlaskalová-Hogenová, Helena; Buschard, K.

    2010-01-01

    Roč. 26, č. 8 (2010), s. 656-667. E-ISSN 1520-7560 R&D Projects: GA ČR GA303/06/1329; GA ČR GA310/07/0414; GA ČR GA310/09/1640 Institutional research plan: CEZ:AV0Z50200510 Keywords : human beta-cell * cd14 * innate immunity Subject RIV: EE - Microbiology, Virology

  9. Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation

    OpenAIRE

    Maria K Magnusson; Brynjólfsson, Siggeir F; Dige, Anders; Uronen-Hansson, Heli; Börjesson, Lars G.; Bengtsson, Jonas L.; Gudjonsson, Sigurdur; Öhman, Lena; Agnholt, Jørgen; Sjövall, Henrik; Agace, William W; Wick, Mary Jo

    2015-01-01

    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 colitis and ulcerative colitis (UC) as well as mesenteric lymph nodes (MLNs) draining these sites. Increased CD14+DRint MQs characterized inflamed intestinal mucosa while total CD141+ or CD1c+ DCs numbers w...

  10. Efficient Feature Subset Selection and Subset Size Optimization

    Czech Academy of Sciences Publication Activity Database

    Somol, Petr; Novovičová, Jana; Pudil, Pavel

    Vukovar, Croatia: In-Teh, 2010 - (Herout, A.), s. 75-98 ISBN 978-953-7619-90-9 R&D Projects: GA MŠk 1M0572; GA ČR GA102/08/0593; GA ČR GA102/07/1594 Grant ostatní: GA MŠk(CZ) 2C06019 Institutional research plan: CEZ:AV0Z10750506 Keywords : dimensionality reduction * pattern recognition * machine learning * feature selection * optimization * subset search * classification Subject RIV: BD - Theory of Information http://library.utia.cas.cz/separaty/2010/RO/somol-efficient feature subset selection and subset size optimization.pdf

  11. Effect of Transcatheter Arterial Chemoembolization Combined with Argon-Helium Cryosurgery System on the Changes of NK Cells and T Cell Subsets in Peripheral Blood of Hepatocellular Carcinoma Patients.

    Science.gov (United States)

    Huang, Manping; Wang, Xiaoyi; Bin, Huang

    2015-12-01

    Hepatocellular carcinoma (HCC) is one of the most aggressive tumors in humans. T lymphocytes and natural killer (NK) cells are the body's first line of defense to prevent tumor cell growth. Previous studies have demonstrated that transcatheter arterial chemoembolization (TACE) combined with argon-helium cryosurgery system (AHCS) can effectively treat liver cancer. However, the mechanism of the treatment is unclear yet. In the current study, we investigated the effects of TACE combined with AHCS on the changes of T cell subsets and NK cells in peripheral blood of HCC. Our data show that alpha-fetoprotein (AFP) levels in peripheral blood were significantly up-regulated in HCC patients before treatment when compared with healthy people and reduced after TACE combined with AHCS treatment (P < 0.01). In addition, we found that CD4+ cells and NK cells decreased (P < 0.05) and CD8+ cells increased (P < 0.05) in HCC patients when compared with healthy people. After treatment, the CD4+ cells, CD4+/CD8+ ratio, and NK cells were dramatically increased in HCC patients (P < 0.05). In contrast, CD8+ cells were significantly decreased (P < 0.05). TACE combined with AHCS treatment significantly prolonged 1-year survival rate of HCC patients and did not show significant side effects. Taken together, our data indicate that TACE combined with AHCS treatment improves patients' immune system. It is a feasible and effective therapeutic method for HCC patients. PMID:27259326

  12. CD16+ Monocyte Subsets Are Increased in Large Abdominal Aortic Aneurysms and Are Differentially Related with Circulating and Cell-Associated Biochemical and Inflammatory Biomarkers

    OpenAIRE

    Giorgio Ghigliotti; Chiara Barisione; Silvano Garibaldi; Claudio Brunelli; Daniela Palmieri; Giovanni Spinella; Bianca Pane; Paolo Spallarossa; Paola Altieri; Patrizia Fabbi; Gianmario Sambuceti; Domenico Palombo

    2013-01-01

    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-inflamma...

  13. Absolute count of T and B lymphocyte subsets is decreased in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Gambichler T

    2010-01-01

    Full Text Available Abstract Background Previous reports on lymphocyte subpopulations in systemic sclerosis (SSc are conflicting. Therefore, we aimed to investigate the lymphocyte subsets in SSc patients who were not on immunosuppressive therapy. Methods Lymphocyte subsets were assessed in the peripheral blood of SSc patients (n = 29 and healthy controls (n = 29 using the four colour flow cytometry method. Correlation studies were also performed in order to assess the relationship between lymphocyte subsets and clinical parameters. Results The absolute count of lymphocytes (P = 0.0042, CD3+ (P = 0.0014, CD4+ (P = 0.0070, CD8+ (P = 0.021, and CD19+ cells (P = 0.024 was significantly decreased in SSc patients when compared to healthy controls. CD4+/CD8+ ratio and the absolute count of CD56+ cells observed in SSc patients did not significantly differ from controls (P = 0.165; P = 0.632, respectively. There was no substantial relationship between the lymphocyte subset levels and clinical features (i.e., SSc subtype, autoantibody profiles, organ involvement, except for a significant inverse correlation of CD19+ cells and the modified Rodnan skin score (r = -0.43, P = 0.020. Conclusion Our data support previous reports indicating that subsets of T lymphocytes as well as B lymphocytes play a role in the pathogenesis of SSc.

  14. Analysis of changes in the percentage of B (CD19) and T (CD3) lymphocytes, nk cells, subsets CD4, CD8 in differentiated thyroid cancer patients treated with iodine-131

    International Nuclear Information System (INIS)

    Objective: To evaluate the changes in the percentage of B (CD19) and T (CD3) lymphocytes, NK cells, subsets CD4, CD8 in patients with differentiated thyroid carcinoma (DTC) who received iodine-131 for therapeutic purposes. Methods: In this study, 102 DTC patients were divided into three groups. Group A, 8 cases received 1850 MBq of iodine-131 for the remnant thyroid ablation. Group B, 43 cases received 3700 MBq of iodine-131 for the treatment of cervical lymph node metastasis. Group C, 51 cases received 7400 MBq of iodine-131 for remote metastasis. All patients were in a hypothyroid state at the time of administration of iodine-131 and resumed L-thyroxine (2μg/Kg/day) 5 days after iodine-131 administration. The percentage of B and T lymphocytes, NK cells, subsets CD4, CD8 in peripheral blood were serially analyzed at baseline and at days 7, 30 and 90 after iodine-131 administration using a Coulter EPICS XL cytometer. Ten healthy individuals were used as a control group for lymphocyte subset values. Results: Comparing the basal lymphocyte subset levels in groups A, B and C with the control group, only NK cells showed significantly higher levels in patients than in controls (P=0.043). In group A, only the percentage of NK cells (P=0.031) and B cells (P =0.024) were reduced at day 7. In group B, a decrease in the percentage of NK cells at days 7(P=0.005), 30 (P=0.021) was observed, while a significant decrease in the percentage of B cells was only observed at day 7(P=0.006). Among T cells, only CD4+ was obviously affected, resulting in a reduction in the CD4+/CD8+ ratio at day 30 (P=0.034). In group C, patients showed a decrease in the percentage of NK cells at days 7 (P=0.023), 30 (P=0.006). A decrease in the percentage of both B and T lymphocytes was observed at days 7(P=0.020, 0.018 respectively), 30(P=0.041, 0.025 respectively). Among T cells, a decrease in the percentage of CD4+ and an increase in the percentage of CD8+ were observed, resulting in a marked

  15. Folliculo-stellate cells of "true dendritic" type are involved in the inflammatory microenvironment of tumor immunosurveillance of pituitary adenomas

    Directory of Open Access Journals (Sweden)

    Kappeler Andreas

    2007-06-01

    Full Text Available Abstract Folliculo-stellate cells are a nonendocrine, sustentacular-like complementary population of the anterior pituitary. They currently are considered as functionally and phenotypically heterogeneous, with one subpopulation of folliculo-stellate cells possibly representing resident adenohypophyseal macrophages. We took advantage of a limited T-cell mediated inflammatory reaction selectively involving tumor tissue in three cases of pituitary adenoma (2 prolactin cell adenomas, and 1 null cell adenoma to test the hypothesis whether some folliculo-stellate cells within inflammatory foci would also assume monocytic/dendritic properties. Immunohistochemical double labeling for S-100 protein and the class II major histocompatibility antigen HLA-DR indeed showed several arborized cells to coexpress both epitopes. These were distributed both amidst adenomatous acini and along intratumoral vessels, and were morphologically undistinguishable from conventional folliculo-stellate cells. On the other hand, markers of follicular dendritic cells (CD21 and Langerhans' cells (CD1a tested negative. Furthermore, no S-100/HLA-DR coexpressing folliculo-stellate cells were seen in either peritumoral parenchyma of the cases in point nor in control pituitary adenomas lacking inflammatory reaction. These findings suggest that a subset of folliculo-stellate cells may be induced by an appropriate local inflammatory microenvironment to assume a dendritic cell-like immunophenotype recognizable by their coexpression of S-100 protein and HLA-DR. By analogy with HLA-DR expressing cells in well-established extrapituitary inflammatory constellations, we speculate that folliculo-stellate cells with such immunophenotype may actually perform professional antigen presentation. A distinctly uncommon finding in pituitary adenomas, lymphocytic infiltrates may therefore be read as a manifestation of tumoral immunosurveillance.

  16. 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.

  17. Transitional Cell Carcinoma Involving the Prostate: Transrectal Grayscale

    International Nuclear Information System (INIS)

    We report here on three cases of prostatic transitional cell carcinoma (TCC), two confirmed by transrectal ultrasonography (TRUS)-guided core biopsy and one by transurethral resection of the prostate. TCC was found in the right distal ureter in one case, in the urinary bladder in another, and was confined within the prostate in the third. On gray-scale ultrasonography (GSUS), two cases showed focal, low echoic lesions in the outer gland, and differentiation between the inner and outer glands was difficult. The third case showed no definite focal prostatic lesion. On color Doppler ultrasonography (CDUS), two cases showed diffusely increased blood flow in the entire prostate, and the third showed focally increased blood flow in the inner gland. The serum prostatic specific antigen (PSA) levels were normal in all three patients. The GSUS and CDUS findings of TCC involving the prostate were similar to those of prostatic cancer. In the case of normal serum PSA levels, the presence of focal, low echoic lesions and increased blood flow of the prostate in those patients with previous or current TCC in the bladder or upper urinary tract may be the distinguishing manifestations of TCC involving the prostate

  18. Median Selection Subset Aggregation for Parallel Inference

    OpenAIRE

    Wang, Xiangyu; Peng, Peichao; Dunson, David

    2014-01-01

    For massive data sets, efficient computation commonly relies on distributed algorithms that store and process subsets of the data on different machines, minimizing communication costs. Our focus is on regression and classification problems involving many features. A variety of distributed algorithms have been proposed in this context, but challenges arise in defining an algorithm with low communication, theoretical guarantees and excellent practical performance in general settings. We propose...

  19. 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. PMID:26545812

  20. 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...

  1. Syncytin is involved in breast cancer-endothelial cell fusions

    OpenAIRE

    Bjerregaard, Bolette; Holck, S.; Christensen, I. J.; Larsson, Lars-Inge

    2006-01-01

    Cancer cells can fuse spontaneously with normal host cells, including endothelial cells, and such fusions may strongly modulate the biological behaviour of tumors. However, the underlying mechanisms are unknown. We now show that human breast cancer cell lines and 63 out of 165 (38%) breast cancer specimens express syncytin, an endogenous retroviral envelope protein, previously implicated in fusions between placental trophoblast cells. Additionally, endothelial and cancer cells are shown to ex...

  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. Protease activation involved in resistance of human cells to x-ray cell killing

    International Nuclear Information System (INIS)

    Little is known of proteases that play roles in the early steps of X-ray irradiation response. In the present study, we first searched for proteases whose activity is induced in human RSa-R cells after X-ray irradiation. The activity was identified as fibrinolytic, using 125I-labeled fibrin as a substrate. Protease samples were prepared by lysation of cells with a buffer containing MEGA-8. RSa-R cells showed an increased level of protease activity 10 min after X-ray (up to 3 Gy) irradiation. We next examined whether this protease inducibility is causally related with the X-ray susceptibility of cells. Leupeptin, a serine-cysteine protease inhibitor, inhibited the protease activity in samples obtained from X-ray-irradiated RSa-R cells. Treatment of RSa-R cells with the inhibitor before and after X-ray irradiation resulted in an increased susceptibility of the cells to X-ray cell killing. However, the treatment of cells with other inhibitors tested did not modulate the X-ray susceptibility. These results suggest that leupeptin-sensitive proteases are involved in the resistance of human cells to X-ray cell killing. (author)

  4. Human Transcription Factor hTAFII150 (CIF150) Is Involved in Transcriptional Regulation of Cell Cycle Progression

    Science.gov (United States)

    Martin, Jay; Halenbeck, Robert; Kaufmann, Jörg

    1999-01-01

    Here we present evidence that CIF150 (hTAFII150), the human homolog of Drosophila TAFII150, plays an important and selective role in establishing gene expression patterns necessary for progression through the cell cycle. Gel filtration experiments demonstrate that CIF150 (hTAFII150) seems to be less tightly associated with human transcription factor IID than hTAFII130 is associated with hTAFII250. The transient functional knockout of CIF150 (hTAFII150) protein led to cell cycle arrest at the G2/M transition in mammalian cell lines. PCR display analysis with the RNA derived from CIF150-depleted cells indicated that CIF150 (hTAFII150) is required for the transcription of only a subset of RNA polymerase II genes. CIF150 (hTAFII150) directly stimulated cyclin B1 and cyclin A transcription in cotransfection assays and in vitro assays, suggesting that the expression of these genes is dependent on CIF150 (hTAFII150) function. We defined a CIF150 (hTAFII150) consensus binding site and demonstrated that a CIF150-responsive cis element is present in the cyclin B1 core promoter. These results suggest that one function of CIF150 (hTAFII150) is to select specific RNA polymerase II core promoter elements involved in cell cycle progression. PMID:10409744

  5. Involvement of Plant Stem Cells or Stem Cell-Like Cells in Dedifferentiation

    OpenAIRE

    Jiang, Fangwei; Feng, Zhenhua; Liu, Hailiang; Zhu, Jian

    2015-01-01

    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 pro...

  6. Concomitant nodal involvement by Langerhans Cell Histiocytosis and Hodgkin Lymphoma

    OpenAIRE

    Geurten, Claire; Thiry, Albert; Jamblin, Paul; Demarche, Martine; Hoyoux, Claire

    2015-01-01

    Introduction : Langerhans cell histiocytosis is defined as a clonal neoplastic proliferation of myeloid dendritic cells that upon activation migrate from the mucosal to lymph nodes. Definitive diagnosis is made by anatomo-pathological and immunohistochemical analysis. Langerhans cell histiocytosis is rarely, yet not exceptionally, found coexisting with other malignant neoplasms, suggesting it might arise in reaction to the cytokinic secretion of malignant cells. Case : We report the case o...

  7. Characterization of four functionally distinct human B-cell subsets that are defined by the expression of CD21 and CD86

    OpenAIRE

    García Márquez, María Alejandra

    2015-01-01

    It is now recognized that B lymphocytes are phenotypically and functionally heterogeneous. In addition to their essential role as antibody producing B cells, they serve as antigen-presenting cells, contribute to immunoregulation and represent an important source of cytokines and chemokines. Although several subpopulations have been identified, a deeper understanding of the role of B cells in the pathophysiology of human diseases has been hampered by the lack of well-defined functional B-cell ...

  8. The pattern of immune cell infiltration in chromoblastomycosis: involvement of macrophage inflammatory protein-1 alpha/CCL3 and fungi persistence Padrão de infiltração de células do sistema imune na cromomicose: envolvimento de MIP-1 alfa da persistência fúngica

    OpenAIRE

    Vanuza Cristina Sá; Tarcília Aparecida Silva; Carmelia Matos Santiago Reis; Fernando Queiroz Cunha; Florêncio Figueiredo; Anamélia Lorenzetti Bocca

    2007-01-01

    Chromoblastomycosis (CR) is a subcutaneous chronic mycosis characterized by a granulomatous inflammatory response. However, little is known regarding the pattern of leukocyte subsets in CR and the pathways involved in their recruitment. The objective of this study was to assess the cellular subsets, chemokine, chemokine receptors and enzymes in CR. The inflammatory infiltrate was characterized by immunohistochemistry using antibodies against macrophages (CD68), Langerhans'cells (S100), lympho...

  9. Involvement of LSECtin in the hepatic natural killer cell response.

    Science.gov (United States)

    Yang, Juntao; Wang, He; Wang, Min; Liu, Biao; Xu, Hui; Xu, Feng; Zhao, Dianyuan; Hu, Bin; Zhao, Na; Wang, Junyi; Liu, Di; Tang, Li; He, Fuchu

    2016-07-15

    Accumulating evidence has indicated that natural killer cells (NK cells) play an important role in immune responses generated in the liver. However, the underlying molecular basis for local immune regulation is poorly understood. Mice were intraperitoneally injected with polyinosinic-polycytidylic acid (PolyI:C) at a dose of 20 mg/kg body wt. The percentage and absolute number of NK cells in the liver were analysed with flow cytometry. LSECtin knockout mice and LSECtin cDNA plasmids were used for analyze the role of LSECtin in hepatic NK cell regulation in vivo. Here, we show that the C-type lectin LSECtin, a member of the DC-SIGN family, is a novel liver regulator for NK cells. LSECtin could bind to NK cells in a carbohydrate-dependent manner and could regulate the number of hepatic NK cells. In the NK cell-mediated acute liver injury model induced with PolyI:C, the exogenous expression of LSECtin accelerated NK cell-induced liver injury, whereas the absence of LSECtin ameliorated this condition. Our results reveal that LSECtin is a novel, liver-specific NK cell regulator that may be a target for the treatment of inflammatory diseases in the liver. PMID:27184407

  10. Polyarthritis in primary Sjögren's syndrome represents a distinct subset with less pronounced B cell proliferation a Dutch cohort with long-term follow-up.

    Science.gov (United States)

    Ter Borg, E J; Kelder, J C

    2016-03-01

    The primary goal was to investigate the differences in patients with and without polyarthritis (PA) in primary Sjögren's syndrome (pSS) in a clinical-based (real-life) setting, with respect to demographic characteristics, cumulative prevalence of other extra-glandular manifestations (EGM), hypergammaglobulinaemia and serological profile. The secondary goal was to describe the characteristics of polyarthritis in our pSS cohort. Patients diagnosed with pSS and polyarthritis but without rheumatoid arthritis (RA)-like changes on X-rays were followed up prospectively from June 1991 until August 2014, with at least one check-up each year. Patients fulfilling the criteria for concomitant connective tissue disorders were excluded. Data were collected with respect to the prevalence of systemic auto-antibodies (anti-nuclear antibodies (ANA), anti-Sjögren's syndrome-related antigen A (anti-SSA), anti-Sjögren's syndrome type B (anti-SSB) and immunoglobulin M-rheumatoid factor (IgM-RF)) and other EGM related to pSS. A total of 134 patients were included for the final analysis. The median follow-up was 86 months (range 0-368 months). Twenty-two patients (16.4 %) had polyarthritis. The prevalence of systemic auto-antibodies including rheumatoid factor did not differ between the two groups. Anti-cyclic citrullinated peptide (CCP) occurred much more frequently in the polyarthritis-positive (PA+) patients (13.7 vs 0.9 %; p = 0.015). Hypergammaglobulinaemia (p = 0.002) and increased levels of IgG (p = 0.013) occurred much less frequently in the PA+ group compared to the polyarthritis-negative (PA-) group. The mean total number of EGM or of any specific EGM did not differ between the two groups. Most patients had a mild, symmetrical PA predominantly involving the finger joints (proximal interphalangeal joints/metacarpophalangeal joints (PIP/MCP)) and/or wrists and/or metatarsophalangeal (MTP) joints. Significant morning stiffness lasting ≥1 h was found

  11. Peripheral T lymphocyte subset imbalances in children with enterovirus 71-induced hand, foot and mouth disease.

    Science.gov (United States)

    Li, Shuxian; Cai, Chunyan; Feng, Jinyan; Li, Xuejing; Wang, Yingshuo; Yang, Jun; Chen, Zhimin

    2014-02-13

    Inflammatory mediators (i.e. cytokines) play a pivotal role in the regulation of pathophysiological processes during EV71-induced hand, foot and mouth disease (HFMD). Different T cell subsets have distinct cytokine secretion profiles, and alteration in the T cell subsets frequency (imbalance) during infection leads to changed cytokine patterns. However, the effects of EV71 infection on T cell subsets were not clear. The objective of this study was to determine whether EV71-induced HFMD can be explained by the emergence of particular T-cell subsets (Th1, Th2, Tc1, Tc2, Th17, Tc17 and Treg cells) and the cytokine they produced (IFN-γ, IL-4, IL-17A and TGF-β1), as well as distinct responses to EV71 infection. We found that when compared to the control group, the percentage of Th1 and Tc1 cells was significantly higher in mild and severe HFMD group. Similar results were found in the Th1/Th2 ratio and IFN-γ levels. On the other hand, the percentage of Th17 cells and IL-17A levels were the highest in severe HFMD cases, and lowest in controls. Similar trend was also found for the Th17/Treg cell ratio. An optimal cutoff value of 2.15% for Th17 cell and 6.72 pg/ml for IL-17A provided a discriminatory value for differentiating the severity of HFMD cases by receiver operating characteristic curve analyses. These findings reveal that the Th1/Th2 and Th17/Treg imbalance exist in HFMD patients, suggesting their involvement in the pathogenesis of EV71 infection, which may have potential value as biomarkers. PMID:24316007

  12. 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

    2016-01-01

    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. PMID:27436361

  13. Detection of Hepatitis B Virus (HBV) Genomes and HBV Drug Resistant Variants by Deep Sequencing Analysis of HBV Genomes in Immune Cell Subsets of HBV Mono-Infected and/or Human Immunodeficiency Virus Type-1 (HIV-1) and HBV Co-Infected Individuals.

    Science.gov (United States)

    Lee, Z; Nishikawa, S; Gao, S; Eksteen, J B; Czub, M; Gill, M J; Osiowy, C; van der Meer, F; van Marle, G; Coffin, C S

    2015-01-01

    The hepatitis B virus (HBV) and the human immunodeficiency virus type 1 (HIV-1) can infect cells of the lymphatic system. It is unknown whether HIV-1 co-infection impacts infection of peripheral blood mononuclear cell (PBMC) subsets by the HBV. Aims To compare the detection of HBV genomes and HBV sequences in unsorted PBMCs and subsets (i.e., CD4+ T, CD8+ T, CD14+ monocytes, CD19+ B, CD56+ NK cells) in HBV mono-infected vs. HBV/HIV-1 co-infected individuals. Methods Total PBMC and subsets isolated from 14 HBV mono-infected (4/14 before and after anti-HBV therapy) and 6 HBV/HIV-1 co-infected individuals (5/6 consistently on dual active anti-HBV/HIV therapy) were tested for HBV genomes, including replication indicative HBV covalently closed circular (ccc)-DNA, by nested PCR/nucleic hybridization and/or quantitative PCR. In CD4+, and/or CD56+ subsets from two HBV monoinfected cases, the HBV polymerase/overlapping surface region was analyzed by next generation sequencing. Results All analyzed whole PBMC from HBV monoinfected and HBV/HIV coinfected individuals were HBV genome positive. Similarly, HBV DNA was detected in all target PBMC subsets regardless of antiviral therapy, but was absent from the CD4+ T cell subset from all HBV/HIV-1 positive cases (P<0.04). In the CD4+ and CD56+ subset of 2 HBV monoinfected cases on tenofovir therapy, mutations at residues associated with drug resistance and/or immune escape (i.e., G145R) were detected in a minor percentage of the population. Summary HBV genomes and drug resistant variants were detectable in PBMC subsets from HBV mono-infected individuals. The HBV replicates in PBMC subsets of HBV/HIV-1 patients except the CD4+ T cell subpopulation. PMID:26390290

  14. Autophagy involved in resveratrol increased radiosensitivity in glioma stem cells

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of Resveratrol combined with X-ray on radiosensitivity in glioma stem cells. Methods: The proliferation inhibition of glioma stem cells induced by X-rays and Resveratrol was assessed with MTT assay. The activation of proapoptotic effect was characterized by Hoechst 33258 stain. MDC stain and Western blot analysis were used to analyze the autophagy mechanism in X-rays-induced death of glioma stem cells. Results: MTT assay indicated that X-rays and Resveratrol decreased the viability of glioma stem cells (P<0.05); we found the proliferative inhibition of glioma stem cells was declined when we used 3-MA to inhibit autophagy(P<0.05). When the cells were treated by the Resveratrol and x-rays, their spherical shape were changed. Apoptosis was induced in glioma stem cells by combined X-rays and Resveratrol as detected by Hoechst 33258 staining. In addition, autophagy was induced in glioma stem cells in the combined treatment group as detected by MDC staining. Western blotting showed that Bcl-2 expression was decreased. in the combined treatment group (P<0.01), and the LC3-Ⅱ expression was increased in the combined treatment group (P<0.01). Conclusion: Resveratrol can increased the radiation sensitivity of glioma stem cells, the apoptosis and autophagy was induced in the glioma stem cells in the combined treatment X-rays and Resveratrol. Our results suggest that autophagy plays an essential role in the regulation of radiosensitization of glioma stem cells. (authors)

  15. Co-expression network analysis identifies Spleen Tyrosine Kinase (SYK) as a candidate oncogenic driver in a subset of small-cell lung cancer

    OpenAIRE

    Udyavar, Akshata R; Hoeksema, Megan D.; Clark, Jonathan E; Zou, Yong; Tang, Zuojian; Li, Zhiguo; Li, Ming; Chen, Heidi; Statnikov, Alexander; Shyr, Yu; Liebler, Daniel C.; Field, John; Eisenberg, Rosana; Estrada, Lourdes; Massion, Pierre P.

    2013-01-01

    Background Oncogenic mechanisms in small-cell lung cancer remain poorly understood leaving this tumor with the worst prognosis among all lung cancers. Unlike other cancer types, sequencing genomic approaches have been of limited success in small-cell lung cancer, i.e., no mutated oncogenes with potential driver characteristics have emerged, as it is the case for activating mutations of epidermal growth factor receptor in non-small-cell lung cancer. Differential gene expression analysis has al...

  16. Glycosytransferases involved in arabinosylation of cell wall extensins

    DEFF Research Database (Denmark)

    Petersen, Bent L; Harholt, Jesper; Jørgensen, Bodil;

    2011-01-01

    Extensins are a group of ancient hydroxyproline rich cell wall glycoproteins that are found in some chlorophyte algae (such as Chlamydomonas), where they constitute the main wall building block, as well as in higher plant cell walls, where they constitute a relatively minor component of particular...

  17. Target cells involved in radiation and radiation leukemia virus leukemogenesis

    International Nuclear Information System (INIS)

    Comparative studies concerned with the induction and early proliferation phases of preleukemic cells in relation to host environments using radiation or radiation leukemia virus as the leukemogenic agents, indicated different developmental pathways. The lack of thymus in mice exposed to fractionated irradiation did not prevent preleukemic cell induction but did interfere with the incidence of RadLV induced preleukemic cells. Thymus removal within several days following RadLV inoculation prevented the establishment of preleukemic cells in the bone marrow. The radiation induced preleukemic cells in the bone marrow. The radiation induced preleukemic cells were not lysed by anti-Thy-1.2 serum treatment and guinea pig complement whereas the RadLV induced ones were lysed to different degrees. Elimination of Thy-1.2 bearing cells from the virus induced preleukemic population reduced the development of overt T leukemias of donor origin. The thymus seemed of essential importance for establishing the proliferation of RadLV induced preleukemic cells but not for those induced by fractionated irradiation

  18. Genes involved in immortalization of human mammary cells

    Energy Technology Data Exchange (ETDEWEB)

    Stampfer, Martha R.; Yaswen, Paul

    2001-09-27

    Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings of this response. Our data indicate: (1) HMEC acquire the ability to maintain growth in the presence of oncogenic Raf not simply as a consequence of overcoming senescence, but as a result of a newly discovered step in the process of immortal transformation uncovered by our lab, termed conversion. Immortal cells that have not undergone conversion (e.g., cells immortalized by exogenous introduction of the immortalizing enzyme, telomerase) remain growth inhibited. (2) Finite lifespan HMEC growth arrest in response to oncogenic Raf using mediators of growth inhibition that are very different from those used in response to oncogenic Raf by rodent cells and certain other human cell types, including the connective tissue cells from the same breast tissue. While many diverse cell types appear to have in common a tumor-suppressive response to this oncogenic signal, they also have developed multiple mechanisms to elicit this response. Understanding how cancer cells acquire the crucial capacity to be immortal and to abrogate normal tumor-suppressive mechanisms may serve both to increase our understanding of breast cancer progression, and to provide new targets for therapeutic intervention. Our results indicate that normal HMEC have novel means of enforcing a Raf

  19. Langerhans cell histiocytosis involving the liver of a male smoker: a case report

    OpenAIRE

    Savva-Bordalo Joana; Freitas-Silva Margarida

    2008-01-01

    Abstract Introduction Langerhans' cell histiocytosis is a proliferative histiocytic disorder of unknown cause originating from dendritic cells. Case presentation The authors report a case of Langerhans' cell histiocytosis in a 48-year-old man with multisystemic disease presentation, including liver involvement. Conclusion Hepatic involvement is an uncommon feature in this rare disease and there is no consensus on the most effective therapeutic approach.

  20. 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...

  1. Involvement of proliferating cell nuclear antigen (cyclin) in DNA replication in living cells.

    OpenAIRE

    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. We 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 replicatio...

  2. 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.

  3. 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...... FCN1 gene expression largely in myelocytes, metamyelocytes, and band cells with a profile quite similar to that of gelatinase. In accordance with this, biosynthesis studies of neutrophils precursor cells showed that ficolin-1 was primarily synthesized in myelocytes, metamyelocytes, and band cells...

  4. Granular cell tumor with orbital involvement in a child

    International Nuclear Information System (INIS)

    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)

  5. 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)

  6. Neurorestorative Role of Stem Cells in Alzheimer's Disease: Astrocyte Involvement.

    Science.gov (United States)

    Choi, Sung S; Lee, Sang-Rae; Lee, Hong J

    2016-01-01

    Neurogenesis is maintained in both neonatal and adult brain, although it is dramatically reduced in aged neurogenic brain region such as the subgranular layer and subventricular zone of the dentate gyrus (DG). Astrocytes play important roles for survival and maintenance of neurons as well as maintenance of neurogenic niche in quiescent state. Aβ can induce astrocyte activation which give rise to produce reactive oxygen species (ROS) and cytotoxic cytokines and chemokines, and subsequently induce neuronal death. Unfortunately, the current therapeutic medicines have been limited to reduce the symptoms and delay the pathogenesis of Alzheimer's disease (AD), but not to cure it. Stem cells enhance neurogenesis and Aβ clearing as well as improved cognitive impairment. Neurotrophins and growth factors which are produced from both stem cells and astrocytes also have neuroprotective effects via neurogenesis. Secreted factors from both astrocytes and neural stem cells also are influenced in neurogenesis and neuron survival in neurodegenerative diseases. Transplanted stem cells overexpressing neurogenic factors may be an effective and therapeutic tool to enhance neurogenesis for AD. PMID:27018261

  7. Host Cell Factors Involved in the Life Cycle of FMDV

    Science.gov (United States)

    Foot-and-Mouth Disease Virus (FMDV), like other RNA viruses, recruits various host cell factors to assist in translation and replication of the virus genome. While FMDV translation has been extensively investigated, much remains unknown regarding replication of the positive-sense RNA genome. In thi...

  8. 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

    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...... of epigenetic modifiers with a focus on jumonji C enzymes in the development of testicular dysgenesis and germ cell cancer in men....

  9. Altered IgG autoantibody levels and CD4+ T cell subsets in lupus-prone Nba2 mice lacking the nuclear progesterone receptor

    OpenAIRE

    Wong, Alan H.; Agrawal, Nalini; Hughes, Grant C.

    2015-01-01

    Important interactions between female reproduction and autoimmunity are suggested by the female-predominance of systemic lupus erythematosus (SLE) and other autoimmune diseases and the amelioration of certain autoimmune diseases during pregnancy. Sexually dimorphic risk of developing SLE involves modulation of genetic risk by environmental factors, sex hormones and non-hormonal factors encoded on the sex chromosomes. In some lupus models, estrogen, via estrogen receptor alpha (ER-α), enhances...

  10. DEXAMETHASONE DIFFERENTIALLY DOWN-REGULATES L-SELECTIN (CD62L) EXPRESSION BY BOVINE LYMPHOCYTE SUBSETS IN VIVO AND DEPLETES THE INTESTINAL MUCOSA OF INTRAEPITHELIAL GAMMA DELTA CELLS

    Science.gov (United States)

    A hallmark of immune modulation by dexamethasone (DEX) is the suppression of lymphocyte proliferation. DEX also alters the expression of adhesion molecules on bovine lymphocytes. Although intraepithelial lymphocytes (IEL) mainly are non-proliferating cells, we hypothesized that DEX treatment of ca...

  11. Chicken C-type lectin-like receptor B-NK, expressed on NK and T cell subsets, binds to a ligand on activated splenocytes

    Czech Academy of Sciences Publication Activity Database

    Viertiboeck, B.C.; Wortmann, A.; Schmitt, R.; Plachý, Jiří; Gobel, T.W.

    2008-01-01

    Roč. 45, č. 5 (2008), s. 1398-1404. ISSN 0161-5890 Institutional research plan: CEZ:AV0Z50520514 Keywords : Chicken NK cell receptor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.555, year: 2008

  12. 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

    The mechanism of action of methotrexate (MTX) in autoimmune diseases (AID) is unclear. A pro-apoptotic effect has been demonstrated in mitogen-stimulated peripheral blood mononuclear cells (PBMC), but studies employing conventional antigens have disputed a pro-apoptotic effect. CD4+ T helper (Th...

  13. 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.

  14. CXCR7 Is Involved in Human Oligodendroglial Precursor Cell Maturation

    Science.gov (United States)

    Göttle, Peter; Kuhlmann, Tanja; Hartung, Hans-Peter; Antel, Jack; Küry, Patrick

    2016-01-01

    Differentiation of oligodendroglial precursor cells (OPCs), a crucial prerequisite for central nervous system (CNS) remyelination in diseases such as Multiple Sclerosis (MS), is modulated by a multitude of extrinsic and intrinsic factors. In a previous study we revealed that the chemokine CXCL12 stimulates rodent OPC differentiation via activation of its receptor CXCR7. We could now demonstrate that CXCR7 is also expressed on NogoA- and Nkx2.2-positive oligodendroglial cells in human MS brains and that stimulation of cultured primary fetal human OPCs with CXCL12 promotes their differentiation as measured by surface marker expression and morphologic complexity. Pharmacological inhibition of CXCR7 effectively blocks these CXCL12-dependent effects. Our findings therefore suggest that a specific activation of CXCR7 could provide a means to promote oligodendroglial differentiation facilitating endogenous remyelination activities. PMID:26741980

  15. Mediastinal germ cell tumour with massive pulmonary involvement

    OpenAIRE

    Kawamukai, Kenji; Di Saverio, Salomone; Antonacci, Filippo; Lacava, Nicola; Boaron, Maurizio

    2011-01-01

    Multimodality treatment, with chemotherapy and surgery, is potentially curative in case of non-seminomatous germ cell tumours. The authors present the case of a primitive mediastinal GTC with bilateral lung metastases. The patient was treated with five cycles of chemotherapy. Restaging showed reduction of the extent and of 18 FDG intake and β-HCG serum levels. The patient underwent two-step surgical excision of the tumours: mediastinal lesion and 35 lung metastases were resected by a right th...

  16. Involvement of the Tyrosine Kinase Fer in Cell Adhesion

    OpenAIRE

    Rosato, Roberto; Veltmaat, Jacqueline M.; Groffen, John; Heisterkamp, Nora

    1998-01-01

    The Fer protein belongs to the fes/fps family of nontransmembrane receptor tyrosine kinases. Lack of success in attempts to establish a permanent cell line overexpressing it at significant levels suggested a strong negative selection against too much Fer protein and pointed to a critical cellular function for Fer. Using a tetracycline-regulatable expression system, overexpression of Fer in embryonic fibroblasts was shown to evoke a massive rounding up, and the subsequent detachment of the cel...

  17. 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

  18. 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.

  19. Exponentially generic subsets of groups

    CERN Document Server

    Gilman, Robert; Osin, Denis

    2010-01-01

    In this paper we study the generic, i.e., typical, behavior of finitely generated subgroups of hyperbolic groups and also the generic behavior of the word problem for amenable groups. We show that a random set of elements of a nonelementary word hyperbolic group is very likely to be a set of free generators for a nicely embedded free subgroup. We also exhibit some finitely presented amenable groups for which the restriction of the word problem is unsolvable on every sufficiently large subset of words.

  20. 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

  1. A combination HIV reporter virus system for measuring post-entry event efficiency and viral outcome in primary CD4+ T cell subsets

    OpenAIRE

    Tilton, Carisa A.; Tabler, Caroline O.; Lucera, Mark B.; Marek, Samantha L.; Haqqani, Aiman A.; Tilton, John C.

    2013-01-01

    Fusion between the viral membrane of human immunodeficiency virus (HIV) and the host cell marks the end of the HIV entry process and the beginning of a series of post-entry events including uncoating, reverse transcription, integration, and viral gene expression. The efficiency of post-entry events can be modulated by cellular factors including viral restriction factors and can lead to several distinct outcomes: productive, latent, or abortive infection. Understanding host and viral proteins ...

  2. IL-12 immunotherapy of minimal residual disease in murine models of HPV16-associated tumours: induction of immune responses, cytokine production and kinetics of immune cell subsets

    Czech Academy of Sciences Publication Activity Database

    Indrová, Marie; Bieblová, Jana; Bubeník, Jan; Reiniš, Milan

    2008-01-01

    Roč. 32, č. 2 (2008), s. 499-507. ISSN 1019-6439 R&D Projects: GA ČR GA301/06/0774 EU Projects: European Commission(XE) 18933 - CLINIGENE Institutional research plan: CEZ:AV0Z50520514 Keywords : HPV 16 * MHC class I-positive and -deficient tumours * immature myeloid cells Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.234, year: 2008

  3. A Functional Family-Wide Screening of SP/KLF Proteins Identifies a Subset of Suppressors of KRAS-Mediated Cell Growth

    OpenAIRE

    Fernandez-Zapico, Martin E.; Lomberk, Gwen A.; Tsuji, Shoichiro; DeMars, Cathrine J.; Bardsley, Michael R.; Lin,Yi-Hui; Almada, Luciana L.; Han, Jing-Jing; Mukhopadhyay, Debabrata; Ordog, Tamas; Buttar, Navtej S; Urrutia, Raul

    2011-01-01

    SP/KLF transcription factors comprise an emerging group of proteins that may behave as tumor suppressors. Incidentally, many cancers displaying alterations in certain KLF proteins are also associated with a high incidence of KRAS mutations. Therefore, we here investigate whether SP/KLF proteins suppress KRAS-mediated cell growth, and more importantly, the potential mechanisms underlying these effects. Using a comprehensive, family-wide screening of the 24 SP/KLF members, we discover that SP5,...

  4. A subset of asialo GM1+ cells play a protective role in the occurrence of graft-versus-host disease in mice

    International Nuclear Information System (INIS)

    In three different murine models of bone marrow (BM) transplantation the capacity of asialo GM1+ cells to suppress graft-vs-host disease (GVHD) was investigated. In a first model, total lymphoid irradiation (TLI)-treated BALB/C mice were given 1 mg of anti-asialo GM1 antibody. This led to the disappearance of functional suppressor cells after TLI. Injections of anti-asialo GM1 into TLI-treated BALB/C mice before infusion of 30 x 10(6) fully allogeneic (C3H) BM cells, led to a significantly decreased survival rate as compared to TLI-treated mice injected with control serum before BM transplantation (survival 29 and 83%, respectively, at 120 days after transplantation, p = 0.0032 log rank). The mortality of the former group was due to GVHD as 1 degree all dying animals showed clinical and histologic signs of GVHD, 2 degrees all animals were chimeric and 3 degrees mice receiving no or syngeneic BALB/C BM had excellent survival rates excluding BM aplasia or increased susceptibility for infections as reason for the mortality of the allogeneic BM recipients. In a second model, asialo GM1+ cells were removed in vitro from the C3H BM inoculum before injection into lethally irradiated (9 Gy) BALB/C recipients. In mice kept in specific pathogen-free conditions, this procedure resulted into a significant mortality (12/12) as compared to mice receiving BM pretreated with control serum (1/12, p = 0.0001 log rank). When kept in conventional housing, GVHD occurred in both groups but much earlier in the group receiving anti-asialo GM1-treated BM (median survival time 6 vs 46 days for the control mice, p = 0.001 log rank). No animal receiving anti-asialo GM1 and treated with syngeneic BM died, thus excluding toxicity, increased susceptibility to infections, or decreased graft take as a cause of mortality

  5. 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...ruch A, Michiel DF, Oppenheim JJ. J Biol Chem. 1995 May 19;270(20):11703-6. (.png) (.svg) (.html) (.csml) Show Signal...s and receptors involved in recruitment of inflammatory cells. PubmedID 7744810 Title Signals and r

  6. 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.

  7. Susceptibility and Response of Human Blood Monocyte Subsets to Primary Dengue Virus Infection

    OpenAIRE

    Wong, Kok Loon; Chen, Weiqiang; Balakrishnan, Thavamalar; Toh, Ying Xiu; Fink, Katja; Wong, Siew-Cheng

    2012-01-01

    Human blood monocytes play a central role in dengue infections and form the majority of virus infected cells in the blood. Human blood monocytes are heterogeneous and divided into CD16− and CD16+ subsets. Monocyte subsets play distinct roles during disease, but it is not currently known if monocyte subsets differentially contribute to dengue protection and pathogenesis. Here, we compared the susceptibility and response of the human CD16− and CD16+ blood monocyte subsets to primary dengue viru...

  8. Lymphocytic subsets and low-dose exposure

    International Nuclear Information System (INIS)

    The present investigations proved the differential radiosensitivity of lymphocytic subpopulations: From in vivo and in vitro irradiations it may be followed that the most sensitive subset are CD8 positive suppressor T cells. CD4/CD8 ratios are increased both in peripheral blood and after mitogen stimulation of lymphocytes of exposed persons. The decrease in B cells is pronounced only at higher radiation doses. Though the rate of DNA synthesis after mitogen stimulation was reduced in some exposed persons, that was no general phenomenon. Especially after tritium exposure, the observed lymphopenia correlated with an increased stimulation by PHA and an increased rate of DNA synthesis in some probands. Thus the present investigations indicate that - despite an inhibition of some immune parameters by radioexposure - the body is able to maintain its immunological homoeostasis. (authors)

  9. Direct observation of catch bonds involving cell-adhesion molecules

    Science.gov (United States)

    Marshall, Bryan T.; Long, Mian; Piper, James W.; Yago, Tadayuki; McEver, Rodger P.; Zhu, Cheng

    2003-05-01

    Bonds between adhesion molecules are often mechanically stressed. A striking example is the tensile force applied to selectin-ligand bonds, which mediate the tethering and rolling of flowing leukocytes on vascular surfaces. It has been suggested that force could either shorten bond lifetimes, because work done by the force could lower the energy barrier between the bound and free states (`slip'), or prolong bond lifetimes by deforming the molecules such that they lock more tightly (`catch'). Whereas slip bonds have been widely observed, catch bonds have not been demonstrated experimentally. Here, using atomic force microscopy and flow-chamber experiments, we show that increasing force first prolonged and then shortened the lifetimes of P-selectin complexes with P-selectin glycoprotein ligand-1, revealing both catch and slip bond behaviour. Transitions between catch and slip bonds might explain why leukocyte rolling on selectins first increases and then decreases as wall shear stress increases. This dual response to force provides a mechanism for regulating cell adhesion under conditions of variable mechanical stress.

  10. 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

  11. 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.

  12. 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

    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...... 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 0.13±0.15% of CD4(+) T cells (P=0.006) following TT-pulsing. Thyroglobulin-stimulated, IL-10-secreting B cells were enriched within CD5(+) and CD24(high) cells. While thyroglobulin-pulsed B cells induced only modest proliferation of CD4(+) T cells, B cells pulsed with TT induced vigorous...

  13. Oxidative stress induces mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines in a well-matched case control cohort.

    Directory of Open Access Journals (Sweden)

    Shannon Rose

    Full Text Available There is increasing recognition that mitochondrial dysfunction is associated with the autism spectrum disorders. However, little attention has been given to the etiology of mitochondrial dysfunction or how mitochondrial abnormalities might interact with other physiological disturbances associated with autism, such as oxidative stress. In the current study we used respirometry to examine reserve capacity, a measure of the mitochondrial ability to respond to physiological stress, in lymphoblastoid cell lines (LCLs derived from children with autistic disorder (AD as well as age and gender-matched control LCLs. We demonstrate, for the first time, that LCLs derived from children with AD have an abnormal mitochondrial reserve capacity before and after exposure to increasingly higher concentrations of 2,3-dimethoxy-1,4-napthoquinone (DMNQ, an agent that increases intracellular reactive oxygen species (ROS. Specifically, the AD LCLs exhibit a higher reserve capacity at baseline and a sharper depletion of reserve capacity when ROS exposure is increased, as compared to control LCLs. Detailed investigation indicated that reserve capacity abnormalities seen in AD LCLs were the result of higher ATP-linked respiration and maximal respiratory capacity at baseline combined with a marked increase in proton leak respiration as ROS was increased. We further demonstrate that these reserve capacity abnormalities are driven by a subgroup of eight (32% of 25 AD LCLs. Additional investigation of this subgroup of AD LCLs with reserve capacity abnormalities revealed that it demonstrated a greater reliance on glycolysis and on uncoupling protein 2 to regulate oxidative stress at the inner mitochondria membrane. This study suggests that a significant subgroup of AD children may have alterations in mitochondrial function which could render them more vulnerable to a pro-oxidant microenvironment derived from intrinsic and extrinsic sources of ROS such as immune activation and

  14. 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.

  15. 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. PMID:26960711

  16. 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.

  17. 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.

  18. 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...

  19. Identification of Host Proteins Involved in Rickettsial Invasion of Tick Cells

    OpenAIRE

    Petchampai, Natthida; Sunyakumthorn, Piyanate; Banajee, Kaikhushroo H.; Verhoeve, Victoria I.; KEARNEY, MICHAEL T.; Macaluso, Kevin R.

    2014-01-01

    Tick-borne spotted fever group (SFG) Rickettsia species are obligate intracellular bacteria capable of infecting both vertebrate and invertebrate host cells, an essential process for subsequent bacterial survival in distinct hosts. The host cell signaling molecules involved in the uptake of Rickettsia into mammalian and Drosophila cells have been identified; however, invasion into tick cells is understudied. Considering the movement of SFG Rickettsia between vertebrate and invertebrate hosts,...

  20. Functional characterization of human Cd33+ And Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines

    OpenAIRE

    Arger Nicholas; Bingham Brigid; Russell Sarah M; Megiel Carolina; Lechner Melissa G; Woo Tammy; Epstein Alan L

    2011-01-01

    Abstract Background Tumor immune tolerance can derive from the recruitment of suppressor cell populations, including myeloid-derived suppressor cells (MDSC). In cancer patients, MDSC accumulation correlates with increased tumor burden, but the mechanisms of MDSC induction remain poorly understood. Methods This study examined the ability of human tumor cell lines to induce MDSC from healthy donor PBMC using in vitro co-culture methods. These human MDSC were then characterized for morphology, p...

  1. In vivo ultraviolet-exposed human epidermal cells activate T suppressor cell pathways that involve CD4+CD45RA+ suppressor-inducer T cells

    International Nuclear Information System (INIS)

    In vivo UV exposure of human epidermis abrogates the function of CD1+DR+ Langerhans cells and induces the appearance of CD1-DR+ Ag-presenting macrophages. Epidermal cells from UV-exposed skin, in contrast to epidermal cells from normal skin, potently activate autologous CD4+ T cells, and, in particular, the CD45RA+ (2H4+) (suppressor-inducer) subset. We therefore determined whether UV-exposure in humans leads to a T cell response in which suppression dominates. Autologous blood T cells were incubated with epidermal cell suspensions from in vivo UV-irradiated skin. After activation, repurified T cells were transferred in graded numbers to autologous mononuclear cells (MNC) stimulated with PWM and the resultant IgG production analyzed by ELISA. Relative to T cells activated by unirradiated control epidermal cells, T cells activated by UV-exposed epidermal cells demonstrated enhanced capacity to suppress IgG production (n = 6; p less than or equal to 0.03). Within the T cell population, CD8+ cells stimulated by UV-exposed epidermal cells could be directly activated to suppress PWM-stimulated MNC Ig production if IL-2 was provided in the reaction mixture. The suppressive activity was also transferable with purified CD4+ T cells stimulated by UV-exposed epidermal cells (n = 10; p less than or equal to 0.01), and was radiosensitive. Suppression was decreased when PWM-stimulated MNC were depleted of CD8+ T cells before mixing with CD4+ T cells activated by UV-exposed epidermal cells, suggesting indirect induction of CD8+ Ts cells contained within the responding MNC populations. Indeed, physical depletion of CD45RA+ cells resulted in total abrogation of the suppressor function contained in the CD4+ T cells. Activation of suppressor function was critically dependent on DR+ APC contained in UV-exposed epidermis

  2. Calcium Channels are Involved in Calcium Oxalate Crystal Formation in Specialized Cells of Pistia stratiotes L.

    OpenAIRE

    VOLK, GAYLE M.; GOSS, LENORA J.; FRANCESCHI, VINCENT R.

    2004-01-01

    • Background and Aims Pistia stratiotes produces large amounts of calcium (Ca) oxalate crystals in specialized cells called crystal idioblasts. The potential involvement of Ca2+ channels in Ca oxalate crystal formation by crystal idioblasts was investigated.

  3. Identification and Characterization of Genes Involved in Embryonic Crystal Cell Formation During Drosophila Hematopoiesis

    OpenAIRE

    Milchanowski, Allison B.; Henkenius, Amy L.; Narayanan, Maya; Hartenstein, Volker; Banerjee, Utpal

    2004-01-01

    Parallels between vertebrate and Drosophila hematopoiesis add to the value of flies as a model organism to gain insights into blood development. The Drosophila hematopoietic system is composed of at least three classes of terminally differentiated blood cells: plasmatocytes, crystal cells, and lamellocytes. Recent studies have identified transcriptional and signaling pathways in Drosophila involving proteins similar to those seen in human blood development. To identify additional genes involv...

  4. 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 ...

  5. Identification and Characterization of Genes Involved in Embryonic Crystal Cell Formation During Drosophila Hematopoiesis

    Science.gov (United States)

    Milchanowski, Allison B.; Henkenius, Amy L.; Narayanan, Maya; Hartenstein, Volker; Banerjee, Utpal

    2004-01-01

    Parallels between vertebrate and Drosophila hematopoiesis add to the value of flies as a model organism to gain insights into blood development. The Drosophila hematopoietic system is composed of at least three classes of terminally differentiated blood cells: plasmatocytes, crystal cells, and lamellocytes. Recent studies have identified transcriptional and signaling pathways in Drosophila involving proteins similar to those seen in human blood development. To identify additional genes involved in Drosophila hematopoiesis, we have conducted a P-element-based genetic screen to isolate mutations that affect embryonic crystal cell development. Using a marker of terminally differentiated crystal cells, we screened 1040 P-element-lethal lines located on the second and third chromosomes and identified 44 individual lines that affect crystal cell development. Identifying novel genes and pathways involved in Drosophila hematopoiesis is likely to provide further insights into mammalian hematopoietic development and disorders. PMID:15454546

  6. Identification of novel genes involved in the commitment of endodermal cells to the thymic epithelial cell fate

    OpenAIRE

    Mathieu, Yves D.

    2006-01-01

    The thymus provides the microenvironment for the maturation and selection of the majority of peripheral T cells. Endodermal cells of the ventral aspect of the third pharyngeal pouch (3rdpp) at 10.5 days of mouse gestation (E10.5) adopt a thymic epithelial cell fate while cells of the dorsal part of the 3rdpp give rise to the parathyroid glands. To identify novel genes potentially involved in the commitment of endodermal cells to the thymic epithelial cell fate, the transcriptome o...

  7. Aggressive Behavior of a Giant Cell Tumor Involving the Metacarpal Bone During Pregnancy: Case Report

    International Nuclear Information System (INIS)

    Giant cell tumors are benign osteolytic tumors with a variable degree of aggressiveness. We report a rare case of a giant cell tumor involving the metacarpal bone, which was detected during pregnancy and showed rapid progression on a follow-up examination.

  8. Interferon-α induces marked alterations in circulating regulatory T cells, NK cell subsets, and dendritic cells in patients with JAK2V617F-positive essential thrombocythemia and polycythemia vera.

    Science.gov (United States)

    Riley, Caroline H; Brimnes, Marie K; Hansen, Morten; Jensen, Morten Krogh; Hasselbalch, Hans C; Kjaer, Lasse; Straten, Per Thor; Svane, Inge Marie

    2016-07-01

    Long-term therapy with IFN-α2 is associated with sustained major molecular remissions in JAK2-positive ET and PV. The efficacy of IFN-α2 may be partly mediated by modulation of immune cells, which was investigated in twenty patients with ET (n = 6) and PV (n = 14). The frequency of CD4(+) CD25(+) Foxp3(+) T cells was significantly increased during IFN-α2 treatment in all patients (P < 0.0001). A significant expansion of the CD56(bright) NK cells (P = 0.0002) and a concomitant decrease in the frequency of CD56(dim) NK cells (P < 0.0001) were also detected. Myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) were studied in nine patients, and decreased frequencies of both cell types were observed during the course of treatment. On both mDCs and pDCs, HLA-ABC expression was upregulated (P = 0.003), but decreasing expression levels of HLA-DR was detected on mDCs. The expression of CD40 (P = 0.002), CD83 (P = 0.03), and CD86 (P = 0.01) increased, but was confined to pDCs. Furthermore, PD-L1 expression was reduced on mDC (P = 0.003) and increased on pDCs (P = 0.02). No significant correlations were found between the changes in immune cells and hematological or molecular responses achieved in our cohort of patients. So forth, it remains to be revealed whether the profound changes in circulating immune cells contribute to the beneficial effects of long-term IFN-α2 treatment in some patients. PMID:26385526

  9. Interferon-α induces marked alterations in circulating regulatory T cells, NK cell subsets and dendritic cells in patients with JAK2(V617F) -positive essential thrombocythemia and polycythemia vera

    DEFF Research Database (Denmark)

    Riley, Caroline H; Brimnes, Marie K; Hansen, Morten;

    2015-01-01

    DCs) were studied in nine patients and decreased frequencies of both cell types were observed during the course of treatment. On both mDCs and pDCs, HLA-ABC expression was upregulated (P=0.003), but decreasing expression levels of HLA-DR was detected on mDCs. The expression of CD40 (P=0.002), CD83 (P=0......Long-term therapy with IFN-α2 is associated with sustained major molecular remissions in JAK2-positive ET and PV. The efficacy of IFN-α2 may be partly mediated by modulation of immune cells, which was investigated in twenty patients with ET (n= 6) and PV (n=14). The frequency of CD4(+) CD25(+) Foxp......3(+) T cells was significantly increased during IFN-α2 treatment in all patients (P<0.0001). A significant expansion of the CD56(bright) NK cells (P=0.0002) and a concomitant decrease in the frequency of CD56(dim) NK cells (P<0.0001) was also detected. Myeloid DCs (mDCs) and plasmacytoid DCs (p...

  10. 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.

  11. 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.

  12. 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.

  13. 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. PMID:26975014

  14. 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

  15. ADP-ribosylation is involved in the integration of foreign DNA into the mammalian cell genome.

    OpenAIRE

    Farzaneh, F.; Panayotou, G N; Bowler, L. D.; Hardas, B D; Broom, T; Walther, C; Shall, S

    1988-01-01

    The most commonly used DNA transfection method, which employs the calcium phosphate co-precipitation of the donor DNA, involves several discrete steps (1,2). These include the uptake of the donor DNA by the recipient cells, the transport of the DNA to the nucleus, transient expression prior to integration into the host cell genome, concatenation and integration of the transfected DNA into the host cell genome and finally the stable expression of the integrated genes (2,3). Both the concatenat...

  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 ...

  17. T-lymphocyte subsets, thymic size and breastfeeding in infancy

    DEFF Research Database (Denmark)

    Jeppesen, Dorthe Lisbeth; Hasselbalch, Helle; Lisse, Ida M;

    2004-01-01

    We followed the changes in concentration of T-lymphocyte subsets (CD4+ and CD8+ cells) in peripheral blood and thymus size during infancy. Previous studies have found increased thymus size in breastfed infants. The present study analyzed the association between breastfeeding and the number of CD4...

  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)

    Su Liaoyuan; Tian Hailin; Xu Yingdong; Geng Yongzhi

    1998-01-01

    Objective: To determine the NK activity of lymphocyte subsets and the effects of low dose radiation.Methods: Lymphocyte subsets were separated by monoclonal antibodies. The NK activity of each subset on tumor cells was detected by radioactive release method.Results: The results showed that besides NK cells, CD4,CD8 and B cells alone can kill tumor cells. But the cellkilling activity of NK cells appeared to be strongest.There was synergistic effect between CD4 and NK cells.The activity of mixed lymphocytes was more than that of only one subset. The effect of low dose radiation (LDR)on NK activity of panlymphocytes or NK cells was different. Conclusion: This paper demonstrated that NK activity of mononuclear cells was called "NK activity of lymphocytes", but it is not true. Only when NK cells were separated by monoclonal antibodies, its killer activity can be called "activity of NK cells".

  1. The generation of CD8+ T-cell population specific for vaccinia virus epitope involved in the antiviral protection against ectromelia virus challenge.

    Science.gov (United States)

    Gierynska, Malgorzata; Szulc-Dabrowska, Lidia; Dzieciatkowski, Tomasz; Golke, Anna; Schollenberger, Ada

    2015-12-01

    Eradication of smallpox has led to cessation of vaccination programs. This has rendered the human population increasingly susceptible not only to variola virus infection but also to infections with other representatives of Poxviridae family that cause zoonotic variola-like diseases. Thus, new approaches for designing improved vaccine against smallpox are required. Discovering that orthopoxviruses, e.g. variola virus, vaccinia virus, ectromelia virus, share common immunodominant antigen, may result in the development of such a vaccine. In our study, the generation of antigen-specific CD8(+) T cells in mice during the acute and memory phase of the immune response was induced using the vaccinia virus immunodominant TSYKFESV epitope and CpG oligodeoxynucleotides as adjuvants. The role of the generated TSYKFESV-specific CD8(+) T cells was evaluated in mice during ectromelia virus infection using systemic and mucosal model. Moreover, the involvement of dendritic cells subsets in the adaptive immune response stimulation was assessed. Our results indicate that the TSYKFESV epitope/TLR9 agonist approach, delivered systemically or mucosally, generated strong CD8(+) T-cell response when measured 10 days after immunization. Furthermore, the TSYKFESV-specific cell population remained functionally active 2 months post-immunization, and gave cross-protection in virally challenged mice, even though the numbers of detectable antigen-specific T cells decreased. PMID:26474845

  2. Signaling pathways involved in PDGF-evoked cellular responses in human RPE cells

    International Nuclear Information System (INIS)

    We examined whether PDGF may directly stimulate the expression of VEGF by retinal pigment epithelial (RPE) cells in vitro, and the involvement of three signal transduction pathways in the regulation of PDGF-evoked cell proliferation, migration, and production of VEGF-A was investigated. PDGF stimulated the gene and protein expression of VEGF-A by RPE cells, and increased cell proliferation and chemotaxis. PDGF activated all signaling pathways investigated, as determined by increased phosphorylation levels of ERK1/2, p38, and Akt proteins. The three signaling pathways were involved in the mediation of PDGF-evoked cell proliferation, while p38 and PI3K mediated cell migration, and PI3K mediated secretion of VEGF-A. In addition to VEGF-A, the cells expressed mRNAs for various members of the VEGF family and for their receptors, including VEGF-B, -C, -D, flt-1, and KDR. The data indicate that PDGF selectively stimulates the expression of VEGF-A in RPE cells. PDGF evokes at least three signal transduction pathways which are differentially involved in various cellular responses

  3. Changed of NK cell and T-lymphocyte subsets in peripheral blood of patients with brucellosis%布鲁菌病患者外周血NK细胞和T淋巴细胞亚群的变化

    Institute of Scientific and Technical Information of China (English)

    贾宇臣; 其其格; 郭菊红; 赵海珍; 乌云; 奥敦托娅

    2014-01-01

    目的:了解布鲁菌病患者性别、年龄、职业分布特征及并发症,外周血NK细胞和T淋巴细胞亚群的变化及意义。方法对101例布鲁菌病患者采用流行病学调查法进行调查,采用流式细胞仪抗体双表法检测38例布鲁菌病和非布鲁菌病发热患者外周血NK细胞(CD16+CD56+)、淋巴细胞绝对值(CD45+)、T淋巴细胞绝对值(CD3+)、T辅助细胞绝对值(CD3+CD4+)、T抑制/细胞毒细胞绝对值(CD3+CD8+)、B淋巴细胞绝对值(CD19+)、CD4/CD8比值,并进行分析。结果布鲁菌病患者以男性居多,中老年患者居多,发病人群主要为农牧民及从事防疫工作者,并发症以肝功能损害最多;布鲁菌病患者外周血NK绝对值显著低于非布鲁菌病发热患者组,具有统计学意义(t =-2.58,P <0.05)。结论布鲁菌病以男性中老年患者居多,以农牧民和防疫员为主,布鲁菌病患者外周血NK细胞常受损伤。%Objective To investigate the characteristics of gender, age, occupation distributions and complication of patients with brucellosis, explore the changes of NK cell and T-lymphocyte subsets, and the related significance. Methods Total of 101 cases of brucellosis were analyzed by descriptive epidemiological study. NK and T/B-lymphocyte subsets were studied in peripheral blood of 38 patients with brucellosis and 35 cases with non-brucellosis fever. Results The majority of cases were male elderly patients, mainly occurred among farmers, herdsmen and stuff engaged in the epidemic prevention. The complication of brucellosis was priority to liver damage. The number of NK cell in patients with brucellosis was below compared with in patients with non-brucellosis fever, with signiifcant differeces (t=-2.58, P<0.05). Conclusions The majority of patients with brucellosis were male elderly person. Outbreak mainly occur in farmers, herdsmen and stuffs engared in epidemic prevention ifeld

  4. Development of a Synchronous Subset of AADL

    DEFF Research Database (Denmark)

    Filali, Mamoun; Lawall, Julia

    2010-01-01

    We study the definition and the mapping of an AADL subset: the so called synchronous subset. We show that the data port protocol used for delayed and immediate connections between periodic threads can be interpreted in a  synchronous way. In this paper, we formalize this interpretation and study...

  5. Isolated cutaneous involvement in a child with nodal anaplastic large cell lymphoma

    Directory of Open Access Journals (Sweden)

    Vibhu Mendiratta

    2016-01-01

    Full Text Available Non-Hodgkin lymphoma is a common childhood T-cell and B-cell neoplasm that originates primarily from lymphoid tissue. Cutaneous involvement can be in the form of a primary extranodal lymphoma, or secondary to metastasis from a non-cutaneous location. The latter is uncommon, and isolated cutaneous involvement is rarely reported. We report a case of isolated secondary cutaneous involvement from nodal anaplastic large cell lymphoma (CD30 + and ALK + in a 7-year-old boy who was on chemotherapy. This case is reported for its unusual clinical presentation as an acute febrile, generalized papulonodular eruption that mimicked deep fungal infection, with the absence of other foci of systemic metastasis.

  6. REST represses a subset of the pancreatic endocrine differentiation program

    DEFF Research Database (Denmark)

    Martin, David; Kim, Yung-Hae; Sever, Dror;

    2015-01-01

    neurons and in endocrine cells, which is necessary for their normal function. During development, REST represses a subset of genes in the neuronal differentiation program and Rest is down-regulated as neurons differentiate. Here, we investigate the role of REST in the differentiation of pancreatic...... REST is active in pancreas progenitors where it gates the activation of part of the beta cell differentiation program....

  7. Heart of Lymphoma: Primary Mediastinal Large B-Cell Lymphoma with Endomyocardial Involvement

    Directory of Open Access Journals (Sweden)

    Elisa Rogowitz

    2013-01-01

    Full Text Available Primary mediastinal B-cell lymphoma (PMBCL is an uncommon aggressive subset of diffuse large B-cell lymphomas. Although PMBCL frequently spreads locally from the thymus into the pleura or pericardium, it rarely invades directly through the heart. Herein, we report a case of a young Mexican female diagnosed with PMBCL with clear infiltration of lymphoma through the cardiac wall and into the right atrium and tricuspid valve leading to tricuspid regurgitation. This was demonstrated by cardiac MRI and transthoracic echocardiogram. In addition, cardiac MRI and CT scan of the chest revealed the large mediastinal mass completely surrounding and eroding into the superior vena cava (SVC wall causing a collar of stokes. The cardiac and SVC infiltration created a significant therapeutic challenge as lymphomas are very responsive to chemotherapy, and treatment could potentially lead to vascular wall rupture and hemorrhage. Despite the lack of conclusive data on chemotherapy-induced hemodynamic compromise in such scenarios, her progressive severe SVC syndrome and respiratory distress necessitated urgent intervention. In addition to the unique presentation of this rare lymphoma, our case report highlights the safety of R-CHOP treatment.

  8. Acute respiratory distress syndrome due to pulmonary involvement by neoplastic plasma cells in multiple myeloma

    OpenAIRE

    Marmor, D B; Farber, J. L.; Gottlieb, J E

    2006-01-01

    Pulmonary involvement with multiple myeloma occurs infrequently and may be difficult to distinguish from more common primary lung tumours, metastatic disease, or other pleural and parenchymal abnormalities. A patient who developed acute respiratory distress syndrome (ARDS) was subsequently found to have multiple myeloma with involvement of lung parenchyma by neoplastic plasma cells. Only one other report of ARDS in association with multiple myeloma was found, and there are no previous reports...

  9. 复方雷公藤颗粒对再障小鼠骨髓T细胞亚群的影响%Effect of Compound Tripterygium Granule on Bone Marrow T Cell Subsets in Mice Aplastic Anemia Model

    Institute of Scientific and Technical Information of China (English)

    邢海燕; 胡春萍; 蔡雪婷; 胡灿红; 霍介格; 曹鹏; 王志刚

    2012-01-01

    group, but there was no significant difference compared with model group. Compared with the model group, amount of CD4 + , CD8 + , CD4 + /CD8 + in high and low dose group of compound Tripterygium granule was increased, which of CD4+ , CD4 + /CD8+ T cells was significantly different from model group and testosterone undecanoate group (P < 0. 05 ) . Conclusion: Compound Tripterygium granule can regulate the abnormal state of bone marrow T cells, restore balance between T cells and T cell subsets, and promote the recovery of bone marrow function.

  10. Involvement of regulatory volume decrease in the migration of nasopharyngeal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Jian Wen MAO; Li Xin CHEN; Li Wei WANG; Tim JACOB; Xue Rong SUN; Hui LI; Lin Yan ZHU; Pan LI; Ping ZHONG; Si Huai NIE

    2005-01-01

    The transwell chamber migration assay and CCD digital camera imaging techniques were used to investigate the relationship between regulatory volume decrease (RVD) and cell migration in nasopharyngeal carcinoma cells (CNE-2Z cells). Both migrated and non-migrated CNE-2Z cells, when swollen by 47% hypotonic solution, exhibited RVD which was inhibited by extracellular application of chloride channel blockers adenosine 5'-triphosphate (ATP), 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) and tamoxifen. However, RVD rate in migrated CNE-2Z cells was bigger than that of non-migrated cells and the sensitivity of migrated cells to NPPB and tamoxifen was higher than that of nonmigrated cells. ATP, NPPB and tamoxifen also inhibited migration of CNE-2Z cells. The inhibition of migration was positively correlated to the blockage of RVD, with a correlation coefficient (r) = 0.99, suggesting a functional relationship between RVD and cell migration. We conclude that RVD is involved in cell migration and RVD may play an important role in migratory process in CNE-2Z cells.

  11. PD-1HIGH Follicular CD4 T Helper Cell Subsets Residing in Lymph Node Germinal Centers Correlate with B Cell Maturation and IgG Production in Rhesus Macaques

    OpenAIRE

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S.

    2014-01-01

    CD4+ T follicular helper (TFH) cells guide development and maturation of B cells and are crucial for effective antibody responses. Here we found rhesus macaque TFH cells, defined as CXCR5+CD4 T cells, contain two major populations: PD-1INT and PD-1HIGH cells. Of these, PD-1HIGHCD4+ T cells highly co-express ICOS but little CCR7, and reside in lymph node germinal centers (GCs), but not in blood. These cells secrete IL-21 and express transcriptional factor Bcl-6 at higher levels than CXCR5+PD-1...

  12. Systemic Sclerosis Patients Present Alterations in the Expression of Molecules Involved in B-Cell Regulation

    Science.gov (United States)

    Soto, Lilian; Ferrier, Ashley; Aravena, Octavio; Fonseca, Elianet; Berendsen, Jorge; Biere, Andrea; Bueno, Daniel; Ramos, Verónica; Aguillón, Juan Carlos; Catalán, Diego

    2015-01-01

    The activation threshold of B cells is tightly regulated by an array of inhibitory and activator receptors in such a way that disturbances in their expression can lead to the appearance of autoimmunity. The aim of this study was to evaluate the expression of activating and inhibitory molecules involved in the modulation of B cell functions in transitional, naive, and memory B-cell subpopulations from systemic sclerosis patients. To achieve this, blood samples were drawn from 31 systemic sclerosis patients and 53 healthy individuals. Surface expression of CD86, MHC II, CD19, CD21, CD40, CD22, Siglec 10, CD35, and FcγRIIB was determined by flow cytometry. IL-10 production was evaluated by intracellular flow cytometry from isolated B cells. Soluble IL-6 and IL-10 levels were measured by ELISA from supernatants of stimulated B cells. Systemic sclerosis patients exhibit an increased frequency of transitional and naive B cells related to memory B cells compared with healthy controls. Transitional and naive B cells from patients express higher levels of CD86 and FcγRIIB than healthy donors. Also, B cells from patients show high expression of CD19 and CD40, whereas memory cells from systemic sclerosis patients show reduced expression of CD35. CD19 and CD35 expression levels associate with different autoantibody profiles. IL-10+ B cells and secreted levels of IL-10 were markedly reduced in patients. In conclusion, systemic sclerosis patients show alterations in the expression of molecules involved in B-cell regulation. These abnormalities may be determinant in the B-cell hyperactivation observed in systemic sclerosis. PMID:26483788

  13. CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Oue, Erika [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Lee, Ji-Won; Sakamoto, Kei [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Iimura, Tadahiro [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Aoki, Kazuhiro [Section of Pharmacology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Kayamori, Kou [Section of Diagnostic Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Department of Pathology, Ome Municipal General Hospital, Ome, Tokyo (Japan); Michi, Yasuyuki; Yamashiro, Masashi; Harada, Kiyoshi; Amagasa, Teruo [Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Oral cancer cells synthesize CXCL2. Black-Right-Pointing-Pointer CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. Black-Right-Pointing-Pointer CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. Black-Right-Pointing-Pointer We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first

  14. CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

    International Nuclear Information System (INIS)

    Highlights: ► Oral cancer cells synthesize CXCL2. ► CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. ► CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. ► We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction.

  15. Bone marrow-derived cells are differentially involved in pathological and physiological retinal angiogenesis in mice

    International Nuclear Information System (INIS)

    Purpose: Bone marrow-derived cells have been shown to play roles in angiogenesis. Although these cells have been shown to promote angiogenesis, it is not yet clear whether these cells affect all types of angiogenesis. This study investigated the involvement of bone marrow-derived cells in pathological and physiological angiogenesis in the murine retina. Materials and methods: The oxygen-induced retinopathy (OIR) model was used as a retinal angiogenesis model in newborn mice. To block the influence of bone marrow-derived cells, the mice were irradiated with a 4-Gy dose of radiation from a 137Cs source. Irradiation was performed in four different conditions with radio dense 2-cm thick lead disks; (1) H group, the head were covered with these discs to protect the eyes from radiation; (2) A group, all of the body was covered with these discs; (3) N group, mice were completely unshielded; (4) C group, mice were put in the irradiator but were not irradiated. On P17, the retinal areas showing pathological and physiological retinal angiogenesis were measured and compared to the retinas of nonirradiated mice. Results: Although irradiation induced leukocyte depletion, it did not affect the number of other cell types or body weight. Retinal nonperfusion areas were significantly larger in irradiated mice than in control mice (P < 0.05), indicating that physiological angiogenesis was impaired. However, the formation of tuft-like angiogenesis processes was more prominent in the irradiated mice (P < 0.05), indicating that pathological angiogenesis was intact. Conclusions: Bone marrow-derived cells seem to be differentially involved in the formation of physiological and pathological retinal vessels. Pathological angiogenesis in the murine retina does not require functional bone marrow-derived cells, but these cells are important for the formation of physiological vessels. Our results add a new insight into the pathology of retinal angiogenesis and bolster the hypothesis that bone

  16. T cell precursor migration towards beta 2-microglobulin is involved in thymus colonization of chicken embryos

    DEFF Research Database (Denmark)

    Dunon, D; Kaufman, J; Salomonsen, J; Skjoedt, K; Vainio, O; Thiery, J P; Imhof, B A

    1990-01-01

    beta 2-microglobulin (beta 2m) attracts hemopoietic precursors from chicken bone marrow cells in vitro. The cell population responding to beta 2m increases during the second period of thymus colonization, which takes place at days 12-14 of incubation. The precursors from 13.5 day old embryos were...... which suggest that beta 2m mediated chemotaxis is involved in the second wave. Udgivelsesdato: 1990-Oct...

  17. Involvement of Heme Oxygenase-1 in Orexin-A-induced Angiogenesis in Vascular Endothelial Cells

    OpenAIRE

    Kim, Mi-Kyoung; Park, Hyun-Joo; Kim, Su-Ryun; Choi, Yoon Kyung; Bae, Soo-Kyung; Bae, Moon-Kyoung

    2015-01-01

    The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin...

  18. 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...... on the activity of the caspase-8 inhibitor FLIP. Here we show that the Fas pathway also regulates beta cell secretory function. We observed impaired glucose tolerance in Fas-deficient mice due to a delayed and decreased insulin secretory pattern. Expression of PDX-1, a beta cell......-specific transcription factor regulating insulin gene expression and mitochondrial metabolism, was decreased in Fas-deficient beta cells. As a consequence, insulin and ATP production were severely reduced and only partly compensated for by increased beta cell mass. Up-regulation of FLIP enhanced NF-kappaB activity via...

  19. Identification of the cells involved in auxin transport in maize mesocotyl

    Energy Technology Data Exchange (ETDEWEB)

    Jones, A.M. (Univ. of North Carolina, Chapel Hill (USA))

    1989-04-01

    A study was undertaken to identify by a direct method the cells involved in auxin transport through maize mesocotyl tissue. The auxin photoaffinity labeling agent, 7-({sup 3}H), 5-azidoindole 3-acetic acid (N{sub 3}IAA), was loaded into excised stem tissue from a cut end. Polar transport of this analog was demonstrated over 4 hours by comparing uptake into tissue loaded with N{sub 3}IAA from the apical vs. the basal end. Triiodobenzoic acid, an auxin transport inhibitor, inhibited N{sub 3}IAA uptake into tissue. Tissue which had taken up the photoaffinity labeling agent was photolyzed to covalently fix the radioisotope within cells. This tissue was sectioned and subjected to in situ autoradiography. The outermost cell of epidermal tissue and certain files of cells in vascular tissue were densely labeled indicating that on a per cell basis these two cell types are most actively transporting auxin.

  20. Involvement of MAPKs in ICAM-1 Expression in Glomerular Endothelial Cells in Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Watanabe,Naomi

    2011-08-01

    Full Text Available Inflammatory processes are involved in the pathogenesis of diabetic nephropathy. The aim of this study was to clarify the role of mitogen-activated protein kinase (MAPK pathways for induction of intercellular adhesion molecule-1 (ICAM-1 expression in glomerular endothelial cells under diabetic conditions. We examined the expression of ICAM-1 in the kidneys of experimental diabetic rats. Human glomerular endothelial cells (GE cells were exposed to normal glucose concentration, high glucose concentration (HG, or high mannitol concentration (HM, and then the expression of the ICAM-1 protein and the phosphorylation of the 3 subfamilies of mitogen-activated protein kinase (MAPK were determined using Western blot analysis. Next, to evaluate the involvement of MAPKs in HG- or HM-induced ICAM-1 expression, we preincubated GE cells with the inhibitors for ERK, p38 or JNK 1h prior to the application of glucose or mannitol. Expression of ICAM-1 was increased in the glomeruli of diabetic rats. Both HG and HM induced ICAM-1 expression and phosphorylation of ERK1/2, p38 and JNK in GE cells. Expression of ICAM-1 was significantly attenuated by inhibitors of ERK, p38 and JNK. We conclude that activation of ERK1/2, p38 and JNK cascades may be involved in ICAM-1 expression in glomerular endothelial cells under diabetic conditions.

  1. [Unresolved issues in the evaluation of research projects involving induced pluripotent stem cells (iPS)].

    Science.gov (United States)

    Casado, María; de Lecuona, Itziar

    2013-01-01

    This paper identifies problems and analyzes those conflicts posed by the evaluation of research projects involving the collection and use of human induced pluripotent stem cells (iPS) in Spain. Current legislation is causing problems of interpretation, circular and unnecessary referrals, legal uncertainty and undue delays. Actually, this situation may cause a lack of control and monitoring, and even some paralysis in regenerative medicine and cell therapy research, that is a priority nowadays. The analysis of the current legislation and its bioethical implications, led us to conclude that the review of iPS research projects cannot be assimilated to the evaluation of research projects that involve human embryonic stem cell (hESC). In this context, our proposal is based on the review by the Research Ethics Committees and the checkout by the Spanish Comission of Guarantees for Donation and Use of Human Cells and Tissues (CGDUCTH) of human iPS cells research projects. Moreover, this article claims for a more transparent research system, by effectively articulating the Registry on Research Projects. Finally, a model of verification protocol (checklist) for checking out biomedical research projects involving human iPS cells is suggested. PMID:24868955

  2. Intracellular signaling pathways involved in the relaxin-induced proliferation of rat Sertoli cells.

    Science.gov (United States)

    Nascimento, Aline Rosa; Pimenta, Maristela Taliari; Lucas, Thais F G; Royer, Carine; Porto, Catarina Segreti; Lazari, Maria Fatima Magalhaes

    2012-09-15

    Regulation of Sertoli cell number is a key event to determine normal spermatogenesis. We have previously shown that relaxin and its G-protein coupled receptor RXFP1 are expressed in rat Sertoli cells, and that relaxin stimulates Sertoli cell proliferation. This study examined the mechanisms underlying the mitogenic effect of relaxin in a primary culture of Sertoli cells removed from testes of immature rats. Stimulation with exogenous relaxin increased Sertoli cell number and the expression of the proliferating cell nuclear antigen (PCNA), but did not affect the mRNA level of the differentiation markers cadherins 1 and 2. Relaxin-induced Sertoli cell proliferation was blocked by inhibition of MEK/ERK1/2 or PI3K/AKT pathways, but not by inhibition of PKC or EGFR activity. Relaxin induced a rapid and transient activation of ERK1/2 phosphorylation, which was MEK and SRC-dependent, and involved upstream activation of G(i). AKT activation could be detected 5 min after relaxin stimulation, and was still detected after 24h of stimulation with relaxin. Relaxin-induced AKT phosphorylation was G(i)- but not PKA-dependent, and it was blocked by both PI3K and MEK inhibitors. In conclusion, the mitogenic effect of relaxin in Sertoli cell involves coupling to G(i) and activation of both MEK/ERK1/2 and PI3K/AKT pathways. PMID:22819701

  3. ZFPIP/Zfp462 is involved in P19 cell pluripotency and in their neuronal fate

    Energy Technology Data Exchange (ETDEWEB)

    Masse, Julie [CNRS UMR 6061, Institut de Genetique et Developpement de Rennes (IGDR), Rennes (France); Universite de Rennes 1, 35043 Rennes cedex (France); Piquet-Pellorce, Claire [Universite de Rennes 1, 35043 Rennes cedex, EA 4427 SeRAIC (France); Viet, Justine; Guerrier, Daniel; Pellerin, Isabelle [CNRS UMR 6061, Institut de Genetique et Developpement de Rennes (IGDR), Rennes (France); Universite de Rennes 1, 35043 Rennes cedex (France); Deschamps, Stephane, E-mail: stephane.deschamps@univ-rennes1.fr [CNRS UMR 6061, Institut de Genetique et Developpement de Rennes (IGDR), Rennes (France); Universite de Rennes 1, 35043 Rennes cedex (France)

    2011-08-01

    The nuclear zinc finger protein ZFPIP/Zfp462 is an important factor involved in cell division during the early embryonic development of vertebrates. In pluripotent P19 cells, ZFPIP/Zfp462 takes part in cell proliferation, likely via its role in maintaining chromatin structure. To further define the function of ZFPIP/Zfp462 in the mechanisms of pluripotency and cell differentiation, we constructed a stable P19 cell line in which ZFPIP/Zfp462 knockdown is inducible. We report that ZFPIP/Zfp462 was vital for mitosis and self-renewal in pluripotent P19 cells. Its depletion induced substantial decreases in the expression of the pluripotency genes Nanog, Oct4 and Sox2 and was associated with the transient expression of specific neuronal differentiation markers. We also demonstrated that ZFPIP/Zfp462 expression appears to be unnecessary after neuronal differentiation is induced in P19 cells. Taken together, our results strongly suggest that ZFPIP/Zfp462 is a key chromatin factor involved in maintaining P19 pluripotency and in the early mechanisms of neural differentiation but that it is dispensable in differentiated P19 cells.

  4. ZFPIP/Zfp462 is involved in P19 cell pluripotency and in their neuronal fate

    International Nuclear Information System (INIS)

    The nuclear zinc finger protein ZFPIP/Zfp462 is an important factor involved in cell division during the early embryonic development of vertebrates. In pluripotent P19 cells, ZFPIP/Zfp462 takes part in cell proliferation, likely via its role in maintaining chromatin structure. To further define the function of ZFPIP/Zfp462 in the mechanisms of pluripotency and cell differentiation, we constructed a stable P19 cell line in which ZFPIP/Zfp462 knockdown is inducible. We report that ZFPIP/Zfp462 was vital for mitosis and self-renewal in pluripotent P19 cells. Its depletion induced substantial decreases in the expression of the pluripotency genes Nanog, Oct4 and Sox2 and was associated with the transient expression of specific neuronal differentiation markers. We also demonstrated that ZFPIP/Zfp462 expression appears to be unnecessary after neuronal differentiation is induced in P19 cells. Taken together, our results strongly suggest that ZFPIP/Zfp462 is a key chromatin factor involved in maintaining P19 pluripotency and in the early mechanisms of neural differentiation but that it is dispensable in differentiated P19 cells.

  5. Nuclear genes involved in mitochondria-to-nucleus communication in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Gabrielson Edward

    2002-11-01

    Full Text Available Abstract Background The interaction of nuclear and mitochondrial genes is an essential feature in maintenance of normal cellular function. Of 82 structural subunits that make up the oxidative phosphorylation system in the mitochondria, mitochondrial DNA (mtDNA encodes 13 subunits and rest of the subunits are encoded by nuclear DNA. Mutations in mitochondrial genes encoding the 13 subunits have been reported in a variety of cancers. However, little is known about the nuclear response to impairment of mitochondrial function in human cells. Results We isolated a Rho0 (devoid of mtDNA derivative of a breast cancer cell line. Our study suggests that depletion of mtDNA results in oxidative stress, causing increased lipid peroxidation in breast cancer cells. Using a cDNA microarray we compared differences in the nuclear gene expression profile between a breast cancer cell line (parental Rho+ and its Rho0 derivative impaired in mitochondrial function. Expression of several nuclear genes involved in cell signaling, cell architecture, energy metabolism, cell growth, apoptosis including general transcription factor TFIIH, v-maf, AML1, was induced in Rho0 cells. Expression of several genes was also down regulated. These include phospholipase C, agouti related protein, PKC gamma, protein tyrosine phosphatase C, phosphodiestarase 1A (cell signaling, PIBF1, cytochrome p450, (metabolism and cyclin dependent kinase inhibitor p19, and GAP43 (cell growth and differentiation. Conclusions Mitochondrial impairment in breast cancer cells results in altered expression of nuclear genes involved in signaling, cellular architecture, metabolism, cell growth and differentiation, and apoptosis. These genes may mediate the cross talk between mitochondria and the nucleus.

  6. Activation of PPARγ is not involved in butyrate-induced epithelial cell differentiation

    International Nuclear Information System (INIS)

    Histone deacetylase-inhibitors affect growth and differentiation of intestinal epithelial cells by inducing expression of several transcription factors, e.g. Peroxisome proliferator-activated receptor γ (PPARγ) or vitamin D receptor (VDR). While activation of VDR by butyrate mainly seems to be responsible for cellular differentiation, the activation of PPARγ in intestinal cells remains to be elucidated. The aim of this study was to determine the role of PPARγ in butyrate-induced cell growth inhibition and differentiation induction in Caco-2 cells. Treatment with PPARγ ligands ciglitazone and BADGE (bisphenol A diglycidyl) enhanced butyrate-induced cell growth inhibition in a dose- and time-dependent manner, whereas cell differentiation was unaffected after treatment with PPARγ ligands rosiglitazone and MCC-555. Experiments were further performed in dominant-negative PPARγ mutant cells leading to an increase in cell growth whereas butyrate-induced cell differentiation was again unaffected. The present study clearly demonstrated that PPARγ is involved in butyrate-induced inhibition of cell growth, but seems not to play an essential role in butyrate-induced cell differentiation

  7. Tissue Plasminogen Activator Expression Is Restricted to Subsets of Excitatory Pyramidal Glutamatergic Neurons.

    Science.gov (United States)

    Louessard, Morgane; Lacroix, Alexandre; Martineau, Magalie; Mondielli, Gregoire; Montagne, Axel; Lesept, Flavie; Lambolez, Bertrand; Cauli, Bruno; Mothet, Jean-Pierre; Vivien, Denis; Maubert, Eric

    2016-09-01

    Although the extracellular serine protease tissue plasminogen activator (tPA) is involved in pathophysiological processes such as learning and memory, anxiety, epilepsy, stroke, and Alzheimer's disease, information about its regional, cellular, and subcellular distribution in vivo is lacking. In the present study, we observed, in healthy mice and rats, the presence of tPA in endothelial cells, oligodendrocytes, mastocytes, and ependymocytes, but not in pericytes, microglial cells, and astrocytes. Moreover, blockage of the axo-dendritic transport unmasked tPA expression in neurons of cortical and hippocampal areas. Interestingly, combined electrophysiological recordings, single-cell reverse transcription polymerase chain reaction (RT-PCR), and immunohistological analyses revealed that the presence of tPA is restricted to subsets of excitatory pyramidal glutamatergic neurons. We further evidenced that tPA is stored in synaptobrevin-2-positive glutamatergic synaptic vesicles. Based on all these data, we propose the existence of tPA-ergic neurons in the mature brain. PMID:26377106

  8. Extrinsic Factors Involved in the Differentiation of Stem Cells into Insulin-Producing Cells: An Overview

    OpenAIRE

    Wong, Rebecca S. Y.

    2011-01-01

    Diabetes mellitus is a chronic disease with many debilitating complications. Treatment of diabetes mellitus mainly revolves around conventional oral hypoglycaemic agents and insulin replacement therapy. Recently, scientists have turned their attention to the generation of insulin-producing cells (IPCs) from stem cells of various sources. To date, many types of stem cells of human and animal origins have been successfully turned into IPCs in vitro and have been shown to exert glucose-lowering ...

  9. LAMP3 is involved in tamoxifen resistance in breast cancer cells through the modulation of autophagy

    NARCIS (Netherlands)

    Nagelkerke, A.P.; Sieuwerts, A.M.; Bussink, J.; Sweep, F.C.; Look, M.P.; Foekens, J.A.; Martens, J.W.; Span, P.N.

    2014-01-01

    Lysosome-associated membrane protein 3 (LAMP3) is a member of the LAMP-family of proteins, which are involved in the process of autophagy. Autophagy is induced by tamoxifen in breast cancer cells and may contribute to tamoxifen resistance. In this study, the significance of LAMP3 for tamoxifen resis

  10. LAMP3 is involved in tamoxifen resistance in breast cancer cells through the modulation of autophagy

    NARCIS (Netherlands)

    A. Nagelkerke (Anika); A.M. Sieuwerts (Anieta); J. Bussink (Johan); F.C. Sweep (Fred); M.P. Look (Maxime); J.A. Foekens (John); J.W.M. Martens (John); P.N. Span (Paul)

    2014-01-01

    textabstractLysosome-associated membrane protein 3 (LAMP3) is a member of the LAMP-family of proteins, which are involved in the process of autophagy. Autophagy is induced by tamoxifen in breast cancer cells and may contribute to tamoxifen resistance. In this study, the significance of LAMP3 for tam

  11. NDRG2: a Myc-repressed gene involved in cancer and cell stress

    Institute of Scientific and Technical Information of China (English)

    Libo Yao; Jian Zhang; Xuewu Liu

    2008-01-01

    As a master switch for cell proliferation and differentiation,Myc exerts its biological functions mainly through transcriptional regulation of its target genes,which are involved in cells' interaction and communication with their external environment.The N-Myc downstream-regulated gene (NDRG) family is composed ofNDRG1,NDRG2,NDRG3 and NDRG4,which are important in cell proliferation and differentiation.This review summarizes the recent studies on the structure,tissue distribution and functions of NDRG2 that try to show its significance in studying cancer and its therapeutic potential.

  12. Musashi2 modulates K562 leukemic cell proliferation and apoptosis involving the MAPK pathway

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Huijuan; Tan, Shi; Wang, Juan; Chen, Shana; Quan, Jing; Xian, Jingrong; Zhang, Shuai shuai; He, Jingang; Zhang, Ling, E-mail: lingzhang@cqmu.edu.cn

    2014-01-01

    The RNA-binding protein Musashi2 (Msi2) has been identified as a master regulator within a variety of stem cell populations via the regulation of translational gene expression. A recent study has suggested that Msi2 is strongly expressed in leukemic cells of acute myeloid leukemia patients, and elevated Msi2 is associated with poor prognosis. However, the potential role of Msi2 in leukemogenesis is still not well understood. Here, we investigated the effect of Msi2 knockdown on the biological properties of leukemic cells. High expression of Msi2 was found in K562 and KG-1a leukemic cell lines, and low expression was observed in the U937 cell line. We transduced K562 cells with two independent adenoviral shRNA vectors targeting Msi2 and confirmed knockdown of Msi2 at the mRNA and protein levels. Msi2 silencing inhibited cell growth and caused cell cycle arrest by increasing the expression of p21 and decreasing the expression of cyclin D1 and cdk2. In addition, knockdown of Msi2 promoted cellular apoptosis via the upregulation of Bax and downregulation of Bcl-2 expression. Furthermore, Msi2 knockdown resulted in the inactivation of the ERK/MAPK and p38/MAPK pathways, but no remarkable change in p-AKT was observed. These data provide evidence that Msi2 plays an important role in leukemogenesis involving the MAPK signaling pathway, which indicates that Msi2 may be a novel target for leukemia treatment. - Highlights: • Knockdown of Msi2 inhibited K562 cell growth and arrested cell cycle progression. • Knockdown of Msi2 induced K562 cell apoptosis via the regulation of Bax and Bcl-2. • The MAPK pathway was involved in the process of Msi2-mediated leukemogenesis. • Our data indicate that Msi2 is a potential new target for leukemia treatment.

  13. Involvement of IRF4 dependent dendritic cells in T cell dependent colitis

    DEFF Research Database (Denmark)

    Pool, Lieneke; Rivollier, Aymeric Marie Christian; Agace, William Winston

    genetically susceptible individuals and pathogenic CD4+ T cells, which accumulate in the inflamed mucosa, are believed to be key drivers of the disease. While dendritic cells (DCs) are important in the priming of intestinal adaptive immunity and tolerance their role in the initiation and perpetuation of...

  14. Effect of an Activated Platelet Concentrate on Differentiated Cells Involved in Tissue Healing.

    Science.gov (United States)

    Brini, Anna T; Ceci, Caterina; Taschieri, Silvio; Niada, Stefania; Lolato, Alessandra; Giannasi, Chiara; Mortellaro, Carmen; Del Fabbro, Massimo

    2016-05-01

    Tissue healing is a complex process involving several players such as cells and growth factors released from platelets upon activation. Today, platelet concentrates (PCs) are used in many different medical fields including oral, orthopaedic, and reconstructive surgery since they allow growth factors delivery to the injured site, aiming at enhancing tissue regeneration. The purpose of this in vitro study was to evaluate the effect of the acellular plasma of an activated platelet concentrate obtained using a manual protocol, on the proliferation, and biological activity of differentiated cells involved in tissue healing. Human osteoblasts and dermal fibroblasts were grown in serum-free medium supplemented with PC derived from several donors. Human osteoblast and human dermal fibroblast proliferation was assessed by MTT test after 7 days and cells were count up to 12-day incubation. Human osteoblast osteo-differentiation was tested after 7 and 14-day incubation by alkaline phosphatase assay. The addition of PC to the culture medium caused an increased proliferation with respect to cells grown in standard condition. The results of the present study suggest that PC supports the proliferation of terminally differentiated cells involved in wound healing and tissue regeneration, confirming its beneficial clinical application in regenerative therapies. PMID:27054419

  15. Secondary pancreatic involvement by a diffuse large B-cell lymphoma presenting as acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    M Wasif Saif; Sapna Khubchandani; Marek Walczak

    2007-01-01

    Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. More than 50% of patients have some site of extra-nodal involvement at diagnosis,including the gastrointestinal tract and bone marrow.However, a diffuse large B-cell lymphoma presenting as acute pancreatitis is rare. A 57-year-old female presented with abdominal pain and matted lymph nodes in her axilla. She was admitted with a diagnosis of acute pancreatitis. Abdominal computed tomography (CT) scan showed diffusely enlarged pancreas due to infiltrative neoplasm and peripancreatic lymphadenopathy. Biopsy of the axillary mass revealed a large B-cell lymphoma.The patient was classified as stage Ⅳ, based on the Ann Arbor Classification, and as having a high-risk lymphoma,based on the International Prognostic Index. She was started on chemotherapy with CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone). Within a week after chemotherapy, the patient's abdominal pain resolved. Follow-up CT scan of the abdomen revealed a marked decrease in the size of the pancreas and peripancreatic lymphadenopathy. A literature search revealed only seven cases of primary involvement of the pancreas in B-cell lymphoma presenting as acute pancreatitis. However, only one case of secondary pancreatic involvement by B-cell lymphoma presenting as acute pancreatitis has been published. Our case appears to be the second report of such a manifestation.Both cases responded well to chemotherapy.

  16. Involvement of Hydrogen Peroxide in Safingol-Induced Endonuclease G-Mediated Apoptosis of Squamous Cell Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Masakazu Hamada

    2014-02-01

    Full Text Available Safingol, a L-threo-dihydrosphingosine, induced the nuclear translocation of a mitochondrial apoptogenic mediator—endonuclease G (endo G—and apoptosis of human oral squamous cell carcinoma (SCC cells. Upstream mediators remain largely unknown. The levels of hydrogen peroxide (H2O2 in cultured oral SCC cells were measured. Treatment with safingol increased intracellular H2O2 levels but not extracellular H2O2 levels, indicating the production of H2O2. The cell killing effect of safingol and H2O2 was diminished in the presence of reactive oxygen species (ROS scavenger N-acetyl-L-cysteine (NAC. Dual staining of cells with annexin V and propidium iodide (PI revealed that apoptotic cell death occurred by treatment with H2O2 and safingol. The number of apoptotic cells was reduced in the presence of NAC. In untreated cells, endo G distributed in the cytoplasm and an association of endo G with mitochondria was observed. After treatment with H2O2 and safingol, endo G was distributed to the nucleus and cytoplasm, indicating the nuclear translocation of the mitochondrial factor. NAC prevented the increase of apoptotic cells and the translocation of endo G. Knock down of endo G diminished the cell killing effect of H2O2 and safingol. These results suggest that H2O2 is involved in the endo G-mediated apoptosis of oral SCC cells by safingol.

  17. Implications for the offspring of circulating factors involved in beta cell adaptation in pregnancy

    DEFF Research Database (Denmark)

    Nalla, Amarnadh; Ringholm, Lene; Søstrup, Birgitte;

    2014-01-01

    proliferation of rat beta cells was studied using [3H]thymidine incorporation and 5-ethynyl-2'-deoxyuridine proliferation assays. In addition, serum from pregnant and nonpregnant women was fractionated by gel filtration and high performance liquid chromatography. The fractionated serum was screened for......OBJECTIVE: Several studies have shown an increase in beta cell mass during pregnancy. Somatolactogenic hormones are known to stimulate the proliferation of existing beta cells in rodents whereas the mechanism in humans is still unclear. We hypothesize that in addition to somatolactogenic hormones...... there are other circulating factors involved in beta cell adaptation to pregnancy. This study aimed at screening for potential pregnancy-associated circulating beta cell growth factors. SAMPLES: Serum samples from nonpregnant and pregnant women. METHODS: The effect of serum from pregnant women on the...

  18. CT and MR findings of langerhans cell histiocytois involving the spleen: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Pyun, Hae Wook; Kim, Mee Eun; Kim, Jang Ho [Fatima Hospital, Taegu (Korea, Republic of)

    2002-02-01

    Langerhans cell histiocytosis (LCH) is systemic disease resulting from the proliferation and dissemination of abnormal histiocytic cells of the Langerhans cell system. Common sites of involvement include the skin, bone, bone marrow, lung, lymph nodes and central nervous system, and the condition manifests in variety of ways. We present the CT and MR findings of a case of LCH involving the spleen, an organ invloved relatively rarely. Post-contrast CT revealed multiple hypodense nodules. T1-weighted MR images of the spleen depicted no definitive lesion, but T2-weighted images showed abnormal low signals scattered throughout this organ. In addition, post-contrast, fat-saturated T1-weighted MR images lesions showed multiple, low-signal-intensity lesions.

  19. CT and MR findings of langerhans cell histiocytois involving the spleen: a case report

    International Nuclear Information System (INIS)

    Langerhans cell histiocytosis (LCH) is systemic disease resulting from the proliferation and dissemination of abnormal histiocytic cells of the Langerhans cell system. Common sites of involvement include the skin, bone, bone marrow, lung, lymph nodes and central nervous system, and the condition manifests in variety of ways. We present the CT and MR findings of a case of LCH involving the spleen, an organ invloved relatively rarely. Post-contrast CT revealed multiple hypodense nodules. T1-weighted MR images of the spleen depicted no definitive lesion, but T2-weighted images showed abnormal low signals scattered throughout this organ. In addition, post-contrast, fat-saturated T1-weighted MR images lesions showed multiple, low-signal-intensity lesions

  20. Subsets of configurations and canonical partition functions

    DEFF Research Database (Denmark)

    Bloch, J.; Bruckmann, F.; Kieburg, M.;

    2013-01-01

    We explain the physical nature of the subset solution to the sign problem in chiral random matrix theory: the subset sum over configurations is shown to project out the canonical determinant with zero quark charge from a given configuration. As the grand canonical chiral random matrix partition f...... function is independent of the chemical potential, the zero-quark-charge sector provides the full result. © 2013 American Physical Society....