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Sample records for atgam lymphocyte immune

  1. T cell immunity using transgenic B lymphocytes

    Science.gov (United States)

    Gerloni, Mara; Rizzi, Marta; Castiglioni, Paola; Zanetti, Maurizio

    2004-03-01

    Adaptive immunity exists in all vertebrates and plays a defense role against microbial pathogens and tumors. T cell responses begin when precursor T cells recognize antigen on specialized antigen-presenting cells and differentiate into effector cells. Currently, dendritic cells are considered the only cells capable of stimulating T lymphocytes. Here, we show that mature naïve B lymphocytes can be genetically programmed by using nonviral DNA and turned into powerful antigen-presenting cells with a dual capacity of synthesis and presentation of antigen to T cells in vivo. A single i.v. injection of transgenic lymphocytes activates T cell responses reproducibly and specifically even at very low cell doses (102). We also demonstrate that T cell priming can occur in the absence of dendritic cells and results in immunological memory with protective effector functions. These findings disclose aspects in the regulation of adaptive immunity and indicate possibilities for vaccination against viruses and cancer in humans.

  2. Lymphocytes and the Adventitial Immune Response in Atherosclerosis

    Science.gov (United States)

    Campbell, Kirsti A.; Lipinski, Michael J.; Doran, Amanda C.; Skaflen, Marcus D.; Fuster, Valentin; McNamara, Coleen A.

    2012-01-01

    Though much of the research on atherosclerosis has focused on the intimal accumulation of lipids and inflammatory cells, there is an increasing amount of interest in the role of the adventitia in coordinating the immune response in atherosclerosis. In this review of the contributions of the adventitia and adventitial lymphocytes to the development of atherosclerosis, we discuss recent research on the formation and structural nature of adventitial immune aggregates, potential mechanisms of crosstalk between the intima, media, and adventitia, specific contributions of B lymphocytes and T lymphocytes, and the role of the vasa vasorum and surrounding perivascular adipose tissue (PVAT). Furthermore, we highlight techniques for the imaging of lymphocytes in the vasculature. PMID:22427326

  3. Lymphocyte GH-axis hormones in immunity.

    Science.gov (United States)

    Weigent, Douglas A

    2013-01-01

    The production and utilization of common ligands and their receptors by cells of the immune and neuroendocrine systems constitutes a biochemical information circuit between and within the immune and neuroendocrine systems. The sharing of ligands and receptors allows the immune system to serve as the sixth sense notifying the nervous system of the presence of foreign entities. Within this framework, it is also clear that immune cell functions can be altered by neuroendocrine hormones and that cells of the immune system have the ability to produce neuroendocrine hormones. This review summarizes a part of this knowledge with particular emphasis on growth hormone (GH). The past two decades have uncovered a lot of detail about the actions of GH, acting through its receptor, at the molecular and cellular level and its influence on the immune system. The production and action of immune cell-derived GH is less well developed although its important role in immunity is also slowly emerging. Here we discuss the production of GH, GH-releasing hormone (GHRH) and insulin-like growth factor-1 (IGF-1) and their cognate receptors on cells of the immune system and their influence via endocrine/autocrine/paracrine and intracrine pathways on immune function. The intracellular mechanisms of action of immune cell-derived GH are still largely unexplored, and it is anticipated that further work in this particular area will establish an important role for this source of GH in normal physiology and in pathologic situations. PMID:24177252

  4. Theoretical implications of cellular immune reactions against helper lymphocytes infected by an immune system retrovirus.

    Science.gov (United States)

    Reibnegger, G; Fuchs, D; Hausen, A; Werner, E R; Dierich, M P; Wachter, H

    1987-01-01

    The breakdown of the immune system induced by the human immunodeficiency virus might be due to the active immune destruction of human immunodeficiency virus-infected helper T lymphocytes expressing viral antigens. By numerical simulation, we have studied possible consequences that a hypothetical immunodeficiency virus (IDV) may have on the cellular immune response by using a mathematical model. In this model, IDV infects CD4+ (helper) T cells and is actively synthesized by the immunologically activated helper T cells. Infected helper T cells synthesizing IDV express antigenic determinants specific for IDV and trigger a cellular immune response against themselves that is mediated by cytotoxic T cells and cytotoxic macrophages. The dynamic evolution of the model in the case of mixed-type infections with IDV and with another pathogen that evokes a cell-mediated immune response shows strong interactions between both simultaneous infections. The model might be of value to elucidate the dynamics leading to opportunistic infections. Furthermore, a pivotal role for immunological stimulation in the progressive exacerbation of the disease can be demonstrated. PMID:2959958

  5. Isolation of Lymphocytes and Their Innate Immune Characterizations from Liver, Intestine, Lung and Uterus

    Institute of Scientific and Technical Information of China (English)

    Jianhong Zhang; Zhongjun Dong; Rongbin Zhou; Deming Luo; Haiming Wei; Zhigang Tian

    2005-01-01

    In steady-state conditions, the number and distribution of lymphocyte populations are under homeostatic control.New lymphocytes are continuously produced in primary and secondary lymphoid organs and then achieve immune-competence within different tissues, and they must challenge with resident cells for survival. The first step in the study of tissue lymphoid cells is their isolation in intact and viable form appropriate for establishment of in vitro culture systems. For reasons of simplicity, cell purity, cell yields and various purposes, lymphocytes obtained from different tissues in different labs were subjected to diverse protocols. To fully elucidate the nature of the local immune system as well as to adequately study the innate role of lymphocytes in liver, intestine, lung and uterus, we briefly reviewed the characterization of resident lymphocytes, and additional information on those cells from non-lymphoid tissues by using the recommended operation procedure was also presented.

  6. Moderate exercise increases the metabolism and immune function of lymphocytes in rats.

    Science.gov (United States)

    Navarro, Francisco; Bacurau, Aline Villa Nova; Pereira, Guilherme Borges; Araújo, Ronaldo Carvalho; Almeida, Sandro Soares; Moraes, Milton Rocha; Uchida, Marco Carlos; Costa Rosa, Luis Fernando Bicudo Pereira; Navalta, James; Prestes, Jonato; Bacurau, Reury Frank Pereira

    2013-05-01

    Exercise modulates both glucose and glutamine metabolism which influences lymphocyte function. We investigated the influence of chronic moderate exercise on glucose and glutamine metabolism in lymphocytes, the associated influence on proliferation, and cytokine and immunoglobulin production. Male Wistar rats (8 weeks old) were placed in an exercise training group (N = 15, 1 h day(-1) at 60 % VO₂max, 5 days week(-1)) for 8 weeks of exercise, or a sedentary control group. Twenty-four hours following the final training session, lymphocytes were separated, and the incorporation of [U-14C]-glucose, [U-14C]-glutamine, and [2-14C]-thymidine from the supernatant was measured. The activity of glucose-6-phosphate dehydrogenase, hexokinase, and glutaminase was measured. Lymphocytes were stimulated with ConA and LPS and incubated with the Mycobacterium bovis bacille Calmette-Guerin (BCG) vaccine and plasma IgG and IgE were measured. Glutamine metabolism increased in both T and B lymphocytes in the trained group. In the trained group, proliferative capacity increased T lymphocytes under ConA stimulation, and increased B lymphocytes with LPS. There was a significant increase in IL-2 production and decrease in IL-4 in the trained group compared with sedentary controls. IL-2R and TNFR increased in trained rats while IL-4R decreased and were more pronounced in T lymphocytes compared with B lymphocytes. In both lymphocyte subsets, exercise training significantly increased the expression of CD54+ and CD30+ cell markers. Exercise training increased plasma IgG compared with the sedentary group. In conclusion, moderate exercise training improves immune function and metabolism in T and B lymphocytes, reflecting an increased ability to respond to immune challenges. PMID:23212119

  7. Lymphocyte-mediated immune cytotoxicity in dogs infected with virulent canine distemper virus.

    OpenAIRE

    Appel, M J; Shek, W R; Summers, B.A.

    1982-01-01

    Immune lymphocyte-mediated cytotoxicity (ILMC) was evaluated in dogs after intranasal exposure to one of the following three virulent strains of canine distemper virus: Cornell A75/17, Ohio R252, and Snyder Hill. Cytotoxicity was tested with peripheral blood lymphocytes as effector cells and primary dog testicle cells that were matched for histocompatibility as target cells. A strong correlation was found between ILMC and the course of the infection. Dogs that succumbed to encephalitis with a...

  8. Effects of therapeutic irradiation on lymphocytes and immunity

    International Nuclear Information System (INIS)

    The lymphocytotoxic effect of therapeutic irradiation may lead to immune depression. The significance of such effects is yet to be determined in many malignancies, especially in light of the persistant immune depression in many ''cured'' patients. The present review examines the effects of age, type of cancer, and stage of disease as well as the results of immune parameters following radiation therapy. Factors to be considered in both the analysis of present day data and in future studies are also reviewed

  9. Preimmunization of donor lymphocytes enhances antitumor immunity of autologous hematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Lymphopenia-induced homeostatic proliferation (HP) of T cells following autologous hematopoietic stem cell transplantation (HSCT) skews the T-cell repertoire by engaging tumor-associated antigens (TAAs), leading to an induction of antitumor immunity. Here, as the tumor-reactive lymphocytes preferentially proliferate during the condition of HP, we examined whether the priming of a donor lymphocytes to TAAs could enhance HP-induced antitumor immunity in autologous HSCT recipients. First, to examine whether the tumor-bearing condition of donor influences the antitumor effect of HSCT, the lymphocytes isolated from CT26 tumor-bearing mice were infused into lethally irradiated mice. The growth of tumors was substantially suppressed in the mice that received HSCT from a tumor-bearing donor compared with a naïve donor, suggesting that a fraction of donor lymphocytes from tumor-bearing mice are primed in response to TAAs and remain responsive upon transplantation. We previously reported that type I interferon (IFN) maturates the dendritic cells and promotes the priming of T cells. We then investigated whether the further priming of donor cells by IFN-α can strengthen the antitumor effect of HSCT. The intratumoral IFN-α gene transfer significantly increased the number of IFN-γ-positive lymphocytes in response to CT26 cells but not the syngeneic lymphocytes in donor mice. The infusion of primed donor lymphocytes markedly suppressed the tumor growth in recipient mice, and cured 64% of the treated mice. Autologous HSCT with the infusion of primed donor lymphocytes is a promising strategy to induce an effective antitumor immunity for solid cancers

  10. EFFECTS OF INTERFERON THERAPY UPON IMMUNE MARKER PROFILE AND ENZYMATIC ACTIVITY IN PERIPHERAL BLOOD LYMPHOCYTES OF PATIENTS WITH RENAL CANCER

    Directory of Open Access Journals (Sweden)

    L. M. Kurtasova

    2014-01-01

    Full Text Available We have observed forty-four patients with metastatic renal cancer before and after interferon therapy. Immune markers of of peripheral blood lymphocytes were determined by flow cytometry. Activity of NAD (P-dependent dehydrogenase in blood lymphocytes was studied by means of bioluminescence technique. Changes of immune marker profiles and enzymatic activities of peripheral blood lymphocytes were found in patients with renal cancer after a course of interferon therapy.

  11. Effect of Excessive Iodine on Immune Function of Lymphocytes and Intervention with Selenium

    Institute of Scientific and Technical Information of China (English)

    CHEN Xiaoyi; LIU Liegang; YAO Ping; YU Dong; HAO Liping; SUN Xiufa

    2007-01-01

    In order to study the effect of excessive iodine on immune function of lymphocytes and the role of selenium supplementation with excessive iodine intake, the changes of T lymphocyte number, ratio of subsets, activity of natural killer (NK) cells and lymphocytes proliferation response were investigated. 150 female BALB/C mice were randomly divided into 5 groups in terms of their body weight (n=30 in each group), and 10 of each group were taken as one batch for test. Mice in the 5 groups were orally administrated with iodine 0 (group Ⅰ ), 1500 (group Ⅱ), 3000 (group Ⅲ),6000 μg/L (group Ⅳ), iodine 6000 μg/L plus selenium 0.3 mg/L (group Ⅴ) respectively for 30 days.Lymphocyte proliferation response, CD4+/CD8+, Th1/Th2 and the activity of NK cells were measured. CD4+/CD8+ was significantly lower, while lymphocyte proliferation response stronger, and Th1/Th2 and the activity of NK cells significantly higher in group Ⅳ than in group Ⅰ (P<0.01).There was no significant difference in all indexes between group Ⅴ and group Ⅰ (P>0.05). It was suggested that excessive iodine as exogenous chemical materials can induce disorders of T lymphocyte immune function in mice. 0.3 mg/L selenium supplementation can protect mice against toxicity induced by 6000 μg/L iodine.

  12. Role of vitamin D in cytotoxic T lymphocyte immunity to pathogens and cancer.

    Science.gov (United States)

    Sarkar, Surojit; Hewison, Martin; Studzinski, George P; Li, Yan Chun; Kalia, Vandana

    2016-04-01

    The discovery of vitamin D receptor (VDR) expression in immune cells has opened up a new area of research into immunoregulation by vitamin D, a niche that is distinct from its classical role in skeletal health. Today, about three decades since this discovery, numerous cellular and molecular targets of vitamin D in the immune system have been delineated. Moreover, strong clinical associations between vitamin D status and the incidence/severity of many immune-regulated disorders (e.g. infectious diseases, cancers and autoimmunity) have prompted the idea of using vitamin D supplementation to manipulate disease outcome. While much is known about the effects of vitamin D on innate immune responses and helper T (TH) cell immunity, there has been relatively limited progress on the frontier of cytotoxic T lymphocyte (CTL) immunity - an arm of host cellular adaptive immunity that is crucial for the control of such intracellular pathogens as human immunodeficiency virus (HIV), tuberculosis (TB), malaria, and hepatitis C virus (HCV). In this review, we discuss the strong historical and clinical link between vitamin D and infectious diseases that involves cytotoxic T lymphocyte (CTL) immunity, present our current understanding as well as critical knowledge gaps in the realm of vitamin D regulation of host CTL responses, and highlight potential regulatory connections between vitamin D and effector and memory CD8 T cell differentiation events during infections. PMID:26479950

  13. T lymphocytes from mice immunized with irradiated sporozoites eliminated malaria from hepatocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hoffman, S.L.; Isenbarger, D.; Long, G.W.; Sedegah, M.; Szarfman, A.

    1990-01-01

    When mice are immunized with radiation-attenuated sporozoites they are solidly protected against sporozoite challenge by an immune response that has been shown to require CD8+ lymphocytes in several strains of mice. The target of this CD8+ T-cell-dependent immunity has not been established. Immune BALB/c mice were shown to develop malaria-specific. CD8+ T-cell-dependent inflammatory infiltrates in their livers after challenge with Plasmodium berghei sporozoites. Spleen cells from immune BALB/c and C57BL/6 mice eliminated hepatocytes infected with the liver stage of P. berghei in vitro. The activity against infected hepatocytes is not inhibited by antibodies to interferon-y and is not present in culture supernatants. It is generally restricted, an indication that malaria antigens on the hepatocyte surface are recognized by immune T-effector cells.

  14. An Act of Balance Between Adaptive and Maladaptive Immunity in Depression: a Role for T Lymphocytes.

    Science.gov (United States)

    Toben, Catherine; Baune, Bernhard T

    2015-12-01

    Historically the monoaminergic neurotransmitter system, in particular the serotonergic system, was seen as being responsible for the pathophysiology of major depressive disorder (MDD). With the advent of psychoneuroimmunology an important role of the immune system in the interface between the central nervous systems (CNS) and peripheral organ systems has emerged. In addition to the well-characterised neurobiological activities of cytokines, T cell function in the context of depression has been neglected so far. In this review we will investigate the biological roles of T cells in depression. Originally it was thought that the adaptive immune arm including T lymphocytes was excluded from the CNS. It is now clear that peripheral naïve T cells not only carry out continuous surveillance within the brain but also maintain neural plasticity. Furthermore animal studies demonstrate that regulatory T lymphocytes can provide protection against maladaptive behavioural responses associated with depression. Psychogenic stress as a major inducer of depression can lead to transient trafficking of T lymphocytes into the brain stimulating the secretion of certain neurotrophic factors and cytokines. The separate and combined mechanism of CD4 and CD8 T cell activation is likely to determine the response pattern of CNS specific neurokines and neurotrophins. Under chronic stress-induced neuroinflammatory conditions associated with depression, T cell responses may become maladaptive and can be involved in neurodegeneration. Additionally, intracellular adhesion and MHC molecule expression as well as glucocorticoid receptor expression within the brain may play a role in determining T lymphocyte functionality in depression. Taken together, T lymphocyte mechanisms, which confer susceptibility or resilience to MDD, are not yet fully understood. Further insight into the cellular and molecular mechanisms which balance the adaptive and maladaptive roles of T lymphocytes may provide a better

  15. Regulatory T Cells and IL-10 Independently Counterregulate Cytotoxic T Lymphocyte Responses Induced by Transcutaneous Immunization

    OpenAIRE

    Pamela Stein; Michael Weber; Steve Prüfer; Beate Schmid; Edgar Schmitt; Hans-Christian Probst; Ari Waisman; Peter Langguth; Hansjörg Schild; Markus P Radsak

    2011-01-01

    BACKGROUND: The imidazoquinoline derivate imiquimod induces inflammatory responses and protection against transplanted tumors when applied to the skin in combination with a cognate peptide epitope (transcutaneous immunization, TCI). Here we investigated the role of regulatory T cells (T(reg)) and the suppressive cytokine IL-10 in restricting TCI-induced cytotoxic T lymphocyte (CTL) responses. METHODOLOGY/PRINCIPAL FINDINGS: TCI was performed with an ointment containing the TLR7 agonist imiqui...

  16. CD8αα innate-type lymphocytes in the intestinal epithelium mediate mucosal immunity

    OpenAIRE

    Kaer, Luc Van; Scott Algood, Holly M.; Singh, Kshipra; Parekh, Vrajesh V.; Greer, Michael J.; Piazuelo, M. Blanca; Weitkamp, Jörn-Hendrik; Matta, Pranathi; Chaturvedi, Rupesh; Wilson, Keith T.; Olivares-Villagómez, Danyvid

    2014-01-01

    Innate immune responses are critical for mucosal immunity. Here we describe an innate lymphocyte population, iCD8α cells, characterized by expression of CD8α homodimers. iCD8α cells exhibit innate functional characteristics such as the capacity to engulf and kill bacteria. Development of iCD8α cells depends on expression of interleukin-2 receptor γ chain (IL-2Rγc), IL-15, and the major histocompatibility complex (MHC) class Ib protein H2-T3, also known as the thymus leukemia antigen or TL. Wh...

  17. Tumor-Infiltrating Lymphocytes in Triple Negative Breast Cancer: The Future of Immune Targeting

    Science.gov (United States)

    García-Teijido, Paula; Cabal, María Luque; Fernández, Ignacio Peláez; Pérez, Yolanda Fernández

    2016-01-01

    Triple negative breast cancer (TNBC) is a highly heterogeneous tumor. There is increasing evidence of the role of tumor lymphocytic immune infiltrates in this subtype of breast cancer. Robust levels of tumor infiltrating lymphocytes (TILs) have been associated with improved disease-free and overall survival rates in TNBC patients with and without any treatment. Recent efforts have been made to develop a standardized methodology for evaluating TILs. The presence of TILs in the breast tumor microenvironment can also predict responses not only to neoadjuvant but also to adjuvant chemotherapy treatments. High numbers of TILs correlate with increased pathological complete responses (pCR) in TNBC. TILs are prognostic and predictive of response to standard therapies; thus, the immune system appears to play an active role in a subgroup of breast cancer. There is an increasing interest in directly targeting the immune system as part of breast cancer therapy, mainly in patients with TNBC. New immune modulatory agents, including immune checkpoints inhibitors, have shown promising activity in a subgroup of metastatic TNBC. Increased programmed cell death protein 1 ligand (PD-L1) expression on the surface of TNBC provides the rationale for implementing therapeutic strategies targeting the PD-1/PD-L1 axis in TNBC. The programmed cell death protein 1 (PD-1) inhibitor pembrolizumab, and the PD-L1 inhibitor atezolizumab have shown promising results in clinical trials. PMID:27081325

  18. Cell-mediated immune response of synovial fluid lymphocytes to ureaplasma antigen in Reiter's syndrome

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    Pavlica Ljiljana

    2003-01-01

    Full Text Available INTRODUCTION Reiter's syndrome (RS is an seronegative arthritis that occurs after urogenital or enteric infection which in addition with occular and/or mucocutaneous manifestations presents complete form of disease. According to previous understanding arthritis in the RS is the reactive one, which means that it is impossible to isolate its causative agent. However, there are the more and more authors suggesting that arthritis in the urogenital form of disease is caused by the infective agent in the affected joint. This suggestion is based on numerous studies on the presence of Chlmaydia trachomatis and Ureaplasma urealyticum in the inflamed joint by using new diagnostic methods in molecular biology published in the recent literature [1-3]. Besides, numerous studies of the humoral and cell-mediated immune response to "triggering" bacteria in the affected joint have supported previous suggestions [4-7]. Aim of the study was to determine whether synovial fluid T-cells specifically recognize the "triggering" bacteria presumably responsible for the Reiter's syndrome. METHOD The 3H-thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial fluid (SF and from peripheral blood (PB [8]. Ureaplasma antigen and mitogen PHA stimulated lymphocytes in 24 RS patients (24 PB samples, 9 SF samples and the results were compared with those found in 10 patients with rheumatoid arthritis (RA (10 PB samples, 5 SF samples. Preparation of ureaplasma antigen. Ureaplasma was cultured on cell-free liquid medium [9]. Sample of 8 ml was heat-inactivated for 15 minutes at 601C and permanently stirred with magnetic mixer. The sample was centrifuged at 2000 x g for 40 minutes and than deposits carefully carried to other sterile glass tubes (Corex and recentrifuged at 9000 x g for 30 minutes. The deposit was washed 3 times in sterile 0.9% NaCl, and final sediment was resuspended in 1.2 ml sterile 0.9% Na

  19. Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection.

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    Cabral-Piccin, M P; Guillermo, L V C; Vellozo, N S; Filardy, A A; Pereira-Marques, S T; Rigoni, T S; Pereira-Manfro, W F; DosReis, G A; Lopes, M F

    2016-01-01

    Chagas disease is caused by infection with the protozoan Trypanosoma cruzi. CD8 T-lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells affects M1 and M2 macrophage phenotypes. First, we found that CD8 T-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute T. cruzi infection. We show that treatment with anti-Fas ligand (FasL) prevents lymphocyte apoptosis, upregulates type-1 responses to parasite antigens, and reduces infection in macrophages cocultured with activated CD8 T cells. Anti-FasL skews mixed M1/M2 macrophage profiles into polarized M1 phenotype, both in vitro and following injection in infected mice. Moreover, inhibition of T-cell apoptosis induces a broad reprogramming of cytokine responses and improves macrophage-mediated immunity to T. cruzi. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence. PMID:27195678

  20. Effect of lead exposure on the immune function of lymphocytes and erythrocytes in preschool children

    Institute of Scientific and Technical Information of China (English)

    赵正言; 李荣; 孙鹂; 历志玉; 杨茹莱

    2004-01-01

    Objective: To investigate the influence of lead exposure on the immune function of lymphocytes and erythrocytes in preschool children. Materials and methods: A group of 217 children three to six years of age from a rural area were given a thorough physical examination and the concentration of lead in blood samples taken from each subject was determined. The indices of lymphocyte immunity (CD+3CD+4, CD+3CD+8, CD+4CD+8, CD-3CD+19) and erythrocyte immunity (RBC-C3b, RBC-IC, RFER, RFIR, CD35 and its average fluorescence intensity) of 40 children with blood lead levels above 0.483 μmol/L were measured and compared with a control group. Results: The blood lead levels of the 217 children ranged from 0.11 μmol/L to 2.11 μmol/L. The CD+3CD+4and CD+4CD+8 cells were lower (P<0.01) and the CD+3CD+8 cells were higher in the lead-poisoned subjects than those in the control group (P<0.05). CD+3 and CD-3CD+19 did not show significant differences. Although the RBC-C3b rosette forming rate was lower and the RBC-IC rosette forming rate was higher in the lead-poisoned group, this difference could not be shown to be statistically significant (P>0.05). RFIR was found to be lower in the lead-poisoned group (P<0.01). Compared with the control group, the positive rate of CD35 was not found to be significantly different in a group of 25 lead-poisoned children (P>0.05), while the average fluorescence intensity was lower in the lead-poisoned group (P<0.05). Conclusion: Lead exposure can result in impaired immune function of T lymphocytes and erythrocytes in preschool children.

  1. Killer B Lymphocytes and their Fas Ligand Positive Exosomes as Inducers of Immune Tolerance

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    Steven Karl Lundy

    2015-03-01

    Full Text Available Induction of immune tolerance is a key process by which the immune system is educated to modulate reactions against benign stimuli such as self-antigens and commensal microbes. Understanding and harnessing the natural mechanisms of immune tolerance may become an increasingly useful strategy for treating many types of allergic and autoimmune diseases, as well as for improving the acceptance of solid organ transplants. Our laboratory and others have been interested in the natural ability of some B lymphocytes to express the death-inducing molecule Fas ligand (FasL, and their ability to kill T helper (TH lymphocytes. We have recently shown that experimental transformation of human B cells by a non-replicative variant of Epstein-Barr virus (EBV consistently resulted in high expression of functional FasL protein. The production and release of FasL+ exosomes that co-expressed MHC Class II molecules and had the capacity to kill antigen-specific TH cells was also observed. Several lines of evidence indicate that FasL+ B cells and FasL+MHCII+ exosomes have important roles in natural immune tolerance and have a great deal of therapeutic potential. Taken together, these findings suggest that EBV-immortalized human B lymphoblastoid cell lines could be used as cellular factories for FasL+ exosomes, which would be employed to therapeutically establish and/or regain immune tolerance toward specific antigens. The goals of this review are to summarize current knowledge of the roles of FasL+ B cells and exosomes in immune regulation, and to suggest methods of manipulating killer B cells and FasL+ exosomes for clinical purposes.

  2. The effects of ionizing radiation on the B lymphocyte immune system

    International Nuclear Information System (INIS)

    Much of the experimental work concerning the effects of ionizing radiation on the immune system was performed prior to the current developments in immunology. Most of the experiments must be repeated in order to study the radiation effects on defined populations of cells or cooperative immune mechanisms. Nevertheless, it is possible at the present time to conclude that: I) The humoral responses are generally more radiosensitive than the cellular immune responses; II) correspondingly, B lymphocytes are quite radiosensitive and probably are subject to interphase as well as mitotic death following irradiation; III) Conversely, activated B cells such as B lymphoblasts or plasmablasts are radioresistant while non-dividing antibody-synthesizing cells are highly radioresistant. The consequences of the ionizing radiation exposure to the humoral immune system are clearly important. The nature of the alterations or damages caused to the infection related immunity can be measured at two levels: 1) a decrease of specific antibody synthesis and as a consequence, 2) a diminution of all antibody dependent cytotoxicity which can include, directly or indirectly, macrophages, eosinophils, basophils, polymorphonuclear leukocytes, etc. Further studies on all presently evoked aspects are clearly required. (orig./MG)

  3. Effect of cholinomimetics and adrenomimetics on proliferation of mouse B lymphocytes during primary immune response to protein antigen

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    Ado, A.D.; Dontsov, V.I.; Gol' dshtein, M.M.

    1985-12-01

    The aim of this investigation was to study the effect of neurotransmitters on proliferation of B lymphocytes induced by specific antigen. Experiments were carried out on female mice. To estimate proliferative activity, lymphocytes enriched with B cells were incubated in medium 199 for 2 h at 37 degrees C in a dose of 2.10/sup 6/-5.10/sup 6/ cells with 2 microCi of /sup 3/H-(methyl)-thymidine. The effect of acetylcholine on incorporation of /sup 3/H-thymidine into B lymphocytes of mice immunized with different doses of antigen during culture is shown. Discordance of effects of adrenalin and acetylcholine on incorporation of /sup 3/H-thymidine into B lymphocytes of mice immunized with different doses of ovalbumin is also shown.

  4. Serologic markers of effective tumor immunity against chronic lymphocytic leukemia include non-mutated B cell antigens

    OpenAIRE

    Marina, Ovidiu; Hainz, Ursula; Biernacki, Melinda A.; Zhang, Wandi; Cai, Ann; Duke-Cohan, Jonathan S.; Liu, Fenglong; Brusic, Vladimir; Neuberg, Donna; Kutok, Jeffery L.; Alyea, Edwin P.; Canning, Christine M.; Soiffer, Robert J.; Ritz, Jerome; Wu, Catherine J.

    2010-01-01

    Patients with chronic lymphocytic leukemia (CLL) who relapse after allogeneic transplant may achieve durable remission following donor lymphocytes infusion (DLI), demonstrating the potency of donor-derived immunity in eradicating tumor. We sought to elucidate the antigenic basis of the effective graft-versus-leukemia (GvL) responses associated with DLI for the treatment of CLL by analyzing the specificity of plasma antibody responses developing in two DLI-treated patients who achieved long-te...

  5. Surface markers of swine lymphocyte: application to the study of local immune system of mammary and transplanted gut

    International Nuclear Information System (INIS)

    Swine lymphocytes are subdivided into four subsets by means of surface markers: T cells by sheep red blood cell receptors, B cells by C3b receptors, L cells by Fc γ receptors and null cells without receptors. Their distribution, development, function and tissue origin were studied in mammary gland and gut as components of the local immune system from 80 to 113 days of pregnancy. There was a colonization of mammary epithelium by T, B and L lymphocytes with few null cells; during lactation, null cells reappeared and the four lymphocyte subsets were similar in proportion to those seen in blood. Dual origin of mammary lymphocytes from mesenteric (MLN) and inguinal lymph nodes (ILN) was shown after labelling each node by fluorescein or rhodamine, respectively, suggesting that local immune response may not depend solely on oral immunization. Swine treated with cyclosporin A were able to tolerate total gut graft transplantation from semihistocompatible pigs. Labelling of recipient MLN or SLA typing showed that gut grafts were colonized by lymphocytes from the recipient. In addition, there were no detectable changes in lymphocyte subset distribution and function, ie, ability to respond to mitogenic stimulation and to synthetize IL-2

  6. The effect of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide on lymphocyte subsets and humoral immune response in SRBC-immunized mice.

    Science.gov (United States)

    Drynda, Angelika; Obmińska-Mrukowicz, Bożena; Mączyński, Marcin; Ryng, Stanisław

    2015-04-01

    5-Amino-3-methyl-4-isoxazolecarboxylic acid hydrazide is a non-cytotoxic synthetic isoxazole derivative with considerable immunomodulatory properties demonstrated in in vitro experiments. The aim of this study was to investigate the influence of this compound, depending on the dosage and schedule of treatment, on lymphocyte subsets in non-immunized mice and humoral immune response in SRBC (sheep red blood cells)-immunized mice. An analysis of lymphocyte subsets was carried out by flow cytometry, using specific monoclonal antibodies stained with fluorescein isothiocyanate (FITC) or phycoerythrin (PE). In the SRBC-immunized mice, the influence of the compound on the humoral response was determined, depending on the time of administration relative to the antigen. The number of plaque forming cells (PFC) was determined by a local hemolysis technique in an agar gel. Total and 2-mercaptoethanol resistant serum agglutination titers were defined by active hemagglutination test carried out on microplates. The investigated hydrazide was able to modulate the percentage and absolute number of T lymphocyte subsets in the thymus, and T and B lymphocytes in the peripheral lymphatic organs. It also enhanced humoral immune response in SRBC-immunized mice by increasing the number of cells producing hemolytic anti-SRBC antibodies (PFC) and by augmenting the level of total and 2-mercaptoethanol resistant hemagglutinin. The present study showed modulatory effects of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide on lymphocyte subsets and humoral immune response in mice. This compound could be potentially useful for the treatment of autoimmune diseases, infections or as an adjuvant for boosting the efficacy of vaccines. PMID:25572572

  7. Lymphocyte phenotypes in wild-caught rats suggest potential mechanisms underlying increased immune sensitivity in post-industrial environments

    OpenAIRE

    Trama, Ashley M.; Holzknecht, Zoie E.; Thomas, Anitra D.; Su, Kuei-Ying; Lee, Sean M; Foltz, Emily E; Perkins, Sarah E; Lin, Shu S.; Parker, William

    2012-01-01

    The immune systems of wild rats and of laboratory rats can been utilized as models of the human immune system in pre-industrial and post-industrial societies, respectively. In this study, lymphocyte phenotypes in wild rats were broadly characterized, and the results were compared to those obtained by us and by others using cells derived from various strains of laboratory rats. Although not expected, the production of regulatory T cells was not apparently different in wild rats compared to lab...

  8. Immune competence of splenic lymphocytes following graft-vs-host disease in mouse allogeneic radiation chimeras

    International Nuclear Information System (INIS)

    The abnormal immune response of long-term mouse allogeneic chimeras is reflected by qualitative deficiencies in either T or B lymphocytes. The present study was undertaken to determine if a relationship existed between the severity of graft-vs-host disease (GVHD) that these animals had experienced and a functional defect in either the T or B cell population. The in vitro PFC response of chimera spleen cells to sheep red blood cells (SRBC) was evaluated in the presence of normal T or B lymphocytes 4 to 8 months after marrow transplantation and well beyond the GVHD period. In an analysis of several different allogeneic radiation chimeras, our results showed no relationship between the severity of GVHD experienced and the immunologic capacity of either T or B cells. Thus, different chimera combinations showing similar degrees of GVHD were functionally deficient in one or the other of these two cells types or both with no apparent predilection for abnormality in either population. In examining the quantitative in vitro PFC response to sheep RBC by spleen cells from individual chimeras, we found that the number of PFC formed was related to the severity of GVHD experienced by that animal. A general relationship between severity of GVHD and PFC capacity may also exist between chimeras of different genetic combinations. However, this relationship is not precise since gross exceptions occur. Our results, although documenting further the qualitative abnormalities in T and/or B lymphocytes of radiation chimeras, do not reveal the factor or mechanisms by which these cells are made unresponsive. It is suggested that the tolerance-inducing mechanism of these animals, whether it be humoral blocking factors or suppressor cells, is in some way interfering with the collaboration of T and B cells for antibody production

  9. B-lymphocyte differentiation in lethally irradiated and reconstituted mice. II. Recovery of humoral immune responsiveness

    International Nuclear Information System (INIS)

    The recovery of humoral immune responsiveness was studied in lethally irradiated, fetal liver-reconstituted mice. By means of both membrane fluorescence and antibody formation to sheep red blood cells (SRBC) as a functional assay, the rate of recovery of the compartments of B and T lymphocytes was determined in various lymphoid organs. The recovery of the immunoglobulin-positive (B) cell compartment after irradiation and reconstitution started in the spleen. This organ was also found to be the first in which the recovery of the B-cell population was completed. The interval between the recovery of the B-cell population in the spleen and that in the other organs tested was found to increase when the irradiated mice were reconstituted with spleen colony cells instead of fetal liver cells. This proved to be caused by the number and nature of the reconstituting hemopoietic stem cells. The immunoglobulin-positive (B) cells were found to appear before SRBC-reactive B cells could be demonstrated in spleen, lymph nodes, and Peyer's patches. The appearance of T lymphocytes in the various lymphoid organs required even more time. By means of cell transfer experiments, a sequential appearance of the precursors of anti-SRBC IgM-, IgG-, and IgA-plaque-forming cells could be demonstrated in spleen, bone marrow, lymph nodes, and Peyer's patches

  10. CD4+CD25+ T lymphocytes and regulation of the immune system: perspectives for a pathophysiological understanding of sepsis.

    Science.gov (United States)

    Siqueira-Batista, Rodrigo; Gomes, Andréia Patrícia; Azevedo, Sarah Fumian Milward; Vitorino, Rodrigo Roger; Mendonça, Eduardo Gomes de; Sousa, Flávio Oliveira de; Oliveira, Alcione de Paiva; Cerqueira, Fábio Ribeiro; Paula, Sérgio Oliveira de; Oliveira, Maria Goreti de Almeida

    2012-09-01

    The systemic inflammatory response represents the core pathogenic event of sepsis, underlying clinical manifestations and laboratory findings in patients. Numerous studies have shown that CD4+CD25+ T lymphocytes, also known as regulatory T lymphocytes (Treg), participate in the development of sepsis due to their ability to suppress the immune response. The present article discusses the role of Treg lymphocytes in sepsis based on a specific search strategy (Latin American and Caribbean Health Sciences / Literatura Latino-americana e do Caribe em Ciências da Saúde - LILACS, PubMed, and Scientific Electronic Library Online - SciELO) focusing on two main topics: the participation of Treg cells in inflammation and immunity as well as perspectives in the computational physiological investigation of sepsis. PMID:23917832

  11. Antigen-specific lymphocyte proliferation as a marker of immune response in guinea pigs with sustained Helicobacter pylori infection.

    Science.gov (United States)

    Miszczyk, Eliza; Walencka, Maria; Rudnicka, Karolina; Matusiak, Agnieszka; Rudnicka, Wiesława; Chmiela, Magdalena

    2014-01-01

    Helicobacter pylori (H. pylori) bacteria are human pathogens causing symptomatic gastritis, peptic ulcer or gastric cancer. Little is known about the kinetics of immune responses in H. pylori infected patients because the initial moment of infection has not been identified. Various animal models are used to investigate the immune processes related to H. pylori infection. In this study we checked whether H. pylori infection in guinea pigs, mimicking natural H. pylori infection in humans, resulted in the development of specific immune responses to H. pylori antigens by measuring the proliferation of lymphocytes localized in mesenteric lymph nodes, spleen and peripheral blood. The maturity of macrophages and cytokines, delivered by monocyte-macrophage lineage or lymphocytes, were considered as mediators, which might influence the lymphocyte blastogenic response. The obtained results showed the activation of T cells localized in mesenteric lymph nodes by H. pylori antigens in H. pylori infected guinea pigs four weeks postinfection. The blastogenic activity of lymphocytes was shaped by their interaction with antigen presenting cells, which were present in the cell cultures during the whole culture period. Moreover, the balance between cytokines derived from adherent leukocytes including interleukin 8--IL-8 as well as interferon gamma--IFN-γ, and transforming growth factor beta--TGF-β delivered by lymphocytes, was probably important for the successful proliferation of lymphocytes. The H. pylori specific lymphocytes were not propagated in peripheral blood and spleen of H. pylori infected animals. The modulation of immunocompetent cells by H. pylori antigens or their different distribution cannot be excluded. PMID:24918491

  12. Altered Innate and Lymphocytic Immune Responses in Mouse Splenocytes Post-Flight

    Science.gov (United States)

    Hwang, ShenAn; Crucian, Brian E.; Sams, Clarence F.; Actor, Jeffrey K.

    2011-01-01

    Space flight is known to affect immune responses of astronauts and animals, decreasing lymphocytic responses to mitogenic stimuli, delayed typed hypersensitivity reactions, and T-cell activation. Despite changes in immune suppression, there are no reports of consistent adverse clinical events post flight. To further investigate the spectrum of affected immune responses, murine splenocytes were stimulated immediately post-shuttle flight (14 days on STS-135) with T-cell stimulators or toll-like receptor agonists. Comparisons were made to ground control splenocytes from age-matched mice. Cell phenotypes were assessed, as well as activation markers and associated cytokine production. The CD4+ population decreased with no concurrent decrease in CD8+ cells from shuttle mice post flight compared to ground controls. Regarding antigen presenting cell populations, the number of CD11c+ cells were slightly elevated post flight, compared to ground controls, with increased MHC Class I expression (I-A(sup b)) and no change in Class II expression (H-2K(sup b)). CD86+ populations were also significantly diminished. However, the decreased markers did not correlate with activity. Stimulation of splenocytes post flight showed significant increase in bead uptake, increased Class I expression, increased TNF-alpha and IL-6 production in response to TLR-2 (zymosan) and TLR-4 (LPS) agonists. While most activated (ConA or anti-CD3/anti-CD28) CD4+ cells showed markedly diminished responses (reduced IL-2 production), non-specific T cell responses to superantigen (SEA/SEB) increased post flight as determined by expression of early activation markers. Production of additional cytokines was also dysregulated postflight. Overall, persistent immune changes during space flight could represent unique clinical risks for exploration class missions. The consequences of pathogenic encounter remain an important concern that should be addressed.

  13. MAJOR LYMPHOCYTE SUBPOPULATIONS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND THEIR ASSOCIATIONS WITH CELLULAR AND HUMORAL ANTI-ENDOTOXIN IMMUNITY

    Directory of Open Access Journals (Sweden)

    D. V. Shaduro

    2015-01-01

    Full Text Available At the present time, systemic lupus erythematosus (SLE takes the leading place among systemic autoimmune disorders. Despite considerable progress in understanding basic pathogenesis of this disease, many subtle mechanisms of progressive inflammation in SLE are still unknown. It has been discovered that the persistent self-maintenance factors of autoimmune inflammation could be represented by lipopolysaccharides or endotoxins of Gram-negative intestinal bacteria. The objective of this study was to assess the levels of major lymphocyte subpopulations, and their probable relation to specific anti-endotoxin antibodies and endotoxin-neutralizing receptors of granulocytes and monocytes in peripheral blood of SLE patients. The study involved forty-eight patients with SLE. The levels of lymphocyte subpopulations, expression of monocyte and granulocyte anti-endotoxin receptors, amounts of total and endotoxin-specific immunoglobulins were determined by means of, respectively, cytometric analysis and enzyme immunoassay techniques. The results of study have shown an increase in overall numbers of activated and cytotoxic T lymphocytes, a decrease in lymphocytes and NK-cells, diminished levels endotoxin-binding receptors on the monocytes and granulocytes, along with increased anti-endotoxin IgG antibodies. Our study revealed correlations between the levels of the leukocyte endotoxin-binding receptors, and B-lymphocyte contents, like as some associations between anti-endotoxin IgM antibodies, and the levels of B-lymphocytes, and cytotoxic T-lymphocytes. A correlation was also found between anti-endotoxin IgG antibodies and CD4+ lymphocyte levels. Significant alterations of the endotoxin-specific immunity among SLE patients suggest that this imbalance might play an important role in the mechanisms of onset and progression of autoimmune diseases.

  14. Regulatory T cells and IL-10 independently counterregulate cytotoxic T lymphocyte responses induced by transcutaneous immunization.

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    Pamela Stein

    Full Text Available BACKGROUND: The imidazoquinoline derivate imiquimod induces inflammatory responses and protection against transplanted tumors when applied to the skin in combination with a cognate peptide epitope (transcutaneous immunization, TCI. Here we investigated the role of regulatory T cells (T(reg and the suppressive cytokine IL-10 in restricting TCI-induced cytotoxic T lymphocyte (CTL responses. METHODOLOGY/PRINCIPAL FINDINGS: TCI was performed with an ointment containing the TLR7 agonist imiquimod and a CTL epitope was applied to the depilated back skin of C57BL/6 mice. Using specific antibodies and FoxP3-diphteria toxin receptor transgenic (DEREG mice, we interrogated inhibiting factors after TCI: by depleting FoxP3(+ regulatory T cells we found that specific CTL-responses were greatly enhanced. Beyond this, in IL-10 deficient (IL-10(-/- mice or after blocking of IL-10 signalling with an IL-10 receptor specific antibody, the TCI induced CTL response is greatly enhanced indicating an important role for this cytokine in TCI. However, by transfer of T(reg in IL-10(-/- mice and the use of B cell deficient JHT(-/- mice, we can exclude T(reg and B cells as source of IL-10 in the setting of TCI. CONCLUSION/SIGNIFICANCE: We identify T(reg and IL-10 as two important and independently acting suppressors of CTL-responses induced by transcutaneous immunization. Advanced vaccination strategies inhibiting T(reg function and IL-10 release may lead the development of effective vaccination protocols aiming at the induction of T cell responses suitable for the prophylaxis or treatment of persistent infections or tumors.

  15. Spontaneous Immunity Against the Receptor Tyrosine Kinase ROR1 in Patients with Chronic Lymphocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    Mohammad Hojjat-Farsangi

    Full Text Available ROR1 is a receptor tyrosine kinase expressed in chronic lymphocytic leukemia (CLL and several other malignancies but absent in most adult normal tissues. ROR1 is considered an onco-fetal antigen. In the present study we analysed spontaneous humoral and cellular immunity against ROR1 in CLL patients.Antibodies against ROR1 were analysed in 23 patients and 20 healthy donors by ELISA and Western blot. Purified serum IgG from patients was tested for cytotoxicity against CLL cells using the MTT viability assay. A cellular immune response against ROR1 derived HLA-A2 restricted 9 aa and 16 aa long peptides were analysed using peptide loaded dendritic cells co-cultured with autologous T cells from CLL patients (n = 9 and healthy donors (n = 6. IFN-γ, IL-5 and IL-17A-secreting T cells were assessed by ELISPOT and a proliferative response using a H3-thymidine incorporation assay.The majority of CLL patients had antibodies against ROR1. Significantly higher titers of anti-ROR1 antibodies were noted in patients with non-progressive as compared to progressive disease. The extracellular membrane-close ROR1 KNG domain seemed to be an immunodominant epitope. Ten patients with high titers of anti-ROR1 binding antibodies were tested for cytotoxicity. Five of those had cytotoxic anti-ROR1 antibodies against CLL cells. ROR1-specific IFN-γ and IL-17A producing T cells could be detected in CLL patients, preferentially in non-progressive as compared to patients with progressive disease (p<0.05.ROR1 seemed to spontaneously induce a humoral as well as a T cell response in CLL patients. The data support the notion that ROR1 might be a specific neo-antigen and may serve as a target for immunotherapy.

  16. Effects of anti-human T lymphocyte immune globulins in patients: new or old.

    Science.gov (United States)

    Wang, Diane C; Wang, Xiangdong; Chen, Chengshui

    2016-09-01

    Multiple studies demonstrated that anti-human T lymphocyte immune globulins (ATG) can decrease the incidence of acute and chronic graft rejection in cell or organ transplants. However, further in-depth study indicates that different subgroups may benefit from either different regimes or alteration of them. Studies among renal transplant patients indicate that low immunological risk patients may not gain the same amount of benefit and thus tilt the risk versus benefit consideration. This may hold true for low immunological risk patients receiving other organ transplants and would be worth further investigation. The recovery time of T cells and natural killer (NK) cells also bears consideration and the impact that it has on the severity and incidence of opportunistic infections closely correlated with the dosage of ATG. The use of lower doses of ATG in combination with other induction medications may offer a solution. The finding that ATG may lose efficacy in cases of multiple transplants or re-transplants in the case of heart transplants may hold true for other transplantations. This may lead to reconsideration of which induction therapies would be most beneficial in the clinical setting. These studies on ATG done on different patient groups will naturally not be applicable to all, but the evidence accrued from them as a whole may offer us new and different perspectives on how to approach and potentially solve the clinical question of how to best reduce the mortality associated with chronic host-versus-graft disease. PMID:27084794

  17. DNA immunization: ubiquitination of a viral protein enhances cytotoxic T-lymphocyte induction and antiviral protection but abrogates antibody induction.

    OpenAIRE

    Rodriguez, F.; Zhang, J.; Whitton, J L

    1997-01-01

    DNA immunization can induce cytotoxic T lymphocytes (CTL), antibodies, and protection against microbial challenge. The underlying mechanisms remain obscure and must be understood to permit rational manipulation and optimization of the technique. We set out to enhance the intracellular degradation of a viral antigen, with the intent of improving antigen entry into, and presentation by, the class I major histocompatibility complex pathway. We achieved this goal by cotranslational ubiquitination...

  18. The pattern recognition molecule ficolin-1 exhibits differential binding to lymphocyte subsets, providing a novel link between innate and adaptive immunity

    DEFF Research Database (Denmark)

    Genster, Ninette; Ma, Ying Jie; Munthe-Fog, Lea; Garred, Peter

    2014-01-01

    -lymphocyte interaction occurred via the pathogen-recognition domain of ficolin-1 to sialic acid on the cell surface. Thus, the differential binding of ficolin-1 to lymphocyte subsets suggests ficolin-1 as a novel link between innate and adaptive immunity. Our results provide new insight about the recognition properties...

  19. In vitro effects of mesenchymal stem cells on secreting function of T lymphocytes and CD4~+CD25~+T cells from patients with immune thrombo-cytopenia

    Institute of Scientific and Technical Information of China (English)

    赵霞

    2014-01-01

    Objective To analyze in vitro the effect of mesenchymal stem cells(MSCs)on secreting cytokines by T lymphocytes and ratio of CD4+CD25+T cells from patients with immune thrombocytopenia(ITP).Methods Human bone marrow-derived MSCs were isolated by Ficoll Hypaque and cultured for proliferating to passage cells.Allogeneic T lymphocytes

  20. Immune Killing Activity of Lymphocytes on Hela Cells Expressing Interleukin-12 In Vitro

    Institute of Scientific and Technical Information of China (English)

    Huiyan WANG; Suhua CHEN

    2008-01-01

    The killing effects of lymphocytes on Hela cells expressing intedeukin-12 (IL-12) in vitro were explored. By using gene transfection technique, full length IL-12 gene was transfected into Hela cells. The expression of IL-12 in Hela cells was detected quantitatively by ELISA; Changes in killing effects of lymphocytes on Hela cells expressing IL-12 were observed by MTT. It was found that Hela cells could express IL-12 between 24h and 72h after transfection. Killing activity of lymphocytes on Hela cells expressing IL-12 was significantly enhanced. It was concluded by cell transfection technique, Hela cells could express IL-12 and were more easily killed by lymphocytes.

  1. De novo transcriptomic analysis of peripheral blood lymphocytes from the Chinese goose: gene discovery and immune system pathway description.

    Directory of Open Access Journals (Sweden)

    Mansoor Tariq

    Full Text Available The Chinese goose is one of the most economically important poultry birds and is a natural reservoir for many avian viruses. However, the nature and regulation of the innate and adaptive immune systems of this waterfowl species are not completely understood due to limited information on the goose genome. Recently, transcriptome sequencing technology was applied in the genomic studies focused on novel gene discovery. Thus, this study described the transcriptome of the goose peripheral blood lymphocytes to identify immunity relevant genes.De novo transcriptome assembly of the goose peripheral blood lymphocytes was sequenced by Illumina-Solexa technology. In total, 211,198 unigenes were assembled from the 69.36 million cleaned reads. The average length, N50 size and the maximum length of the assembled unigenes were 687 bp, 1,298 bp and 18,992 bp, respectively. A total of 36,854 unigenes showed similarity by BLAST search against the NCBI non-redundant (Nr protein database. For functional classification, 163,161 unigenes were comprised of three Gene Ontology (Go categories and 67 subcategories. A total of 15,334 unigenes were annotated into 25 eukaryotic orthologous groups (KOGs categories. Kyoto Encyclopedia of Genes and Genomes (KEGG database annotated 39,585 unigenes into six biological functional groups and 308 pathways. Among the 2,757 unigenes that participated in the 15 immune system KEGG pathways, 125 of the most important immune relevant genes were summarized and analyzed by STRING analysis to identify gene interactions and relationships. Moreover, 10 genes were confirmed by PCR and analyzed. Of these 125 unigenes, 109 unigenes, approximately 87%, were not previously identified in the goose.This de novo transcriptome analysis could provide important Chinese goose sequence information and highlights the value of new gene discovery, pathways investigation and immune system gene identification, and comparison with other avian species as useful

  2. Laser modulation of human immune system: inhibition of lymphocyte proliferation by a gallium-arsenide laser at low energy

    International Nuclear Information System (INIS)

    Cultured human lymphocytes were subjected to irradiation with a gallium-arsenide laser at energy fluence varying from 2.17 to 651 mJ/cm2, and the cell proliferation was assessed by [3H]thymidine incorporation. Both mitogenic proliferation in response to phytohemagglutinin and spontaneous cell proliferation were markedly inhibited by the laser irradiation at energy fluence as low as 10.85 mJ/cm2. Similarly, the functional response of cells to antigen stimulation in a one-way mixed-lymphocyte reaction was also diminished as a result of laser irradiation. The results indicate that laser irradiation at low energy can interfere with immune system in vitro, and similar modulation could potentially occur in human subjects exposed to laser irradiation in vivo

  3. Pharmacokinetics and modeling of immune cell trafficking: quantifying differential influences of target tissues versus lymphocytes in SJL and lipopolysaccharide-treated mice

    Directory of Open Access Journals (Sweden)

    Banks William A

    2012-10-01

    Full Text Available Abstract Background Immune cell trafficking into the CNS and other tissues plays important roles in health and disease. Rapid quantitative methods are not available that could be used to study many of the dynamic aspects of immune cell-tissue interactions. Methods We used pharmacokinetics and modeling to quantify and characterize the trafficking of radioactively labeled lymphocytes into brain and peripheral tissues. We used variance from two-way ANOVAs with 2 × 2 experimental designs to model the relative influences of lymphocytes and target tissues in trafficking. Results We found that in male CD-1 mice, about 1 in 5,000 intravenously injected lymphocytes entered each gram of brain. Uptake by brain was 2 to 3 times higher in naïve SJL females, but uptake by spleen and clearance from blood was lower, demonstrating a dichotomy in immune cell distribution. Treatment of CD-1 mice with lipopolysaccharide (LPS increased immune cell uptake into brain but decreased uptake by spleen and axillary nodes. Conclusions Differences in brain uptake and in uptake by spleen between SJL and CD-1 mice were primarily determined by lymphocytes, whereas differences in uptake with LPS were primarily determined by lymphocytes for the brain but by the tissues for the spleen and the axillary lymph node. These results show that immune cells normally enter the CNS and that tissues and immune cells interact in ways that can be quantified by pharmacokinetic models.

  4. Decreased B and T lymphocyte attenuator in Behcet's disease may trigger abnormal Th17 and Th1 immune responses.

    Science.gov (United States)

    Ye, Zi; Deng, Bolin; Wang, Chaokui; Zhang, Dike; Kijlstra, Aize; Yang, Peizeng

    2016-01-01

    Behcet's disease (BD) is a chronic, systemic and recurrent inflammatory disease associated with hyperactive Th17 and Th1 immune responses. Recent studies have shown that B and T lymphocyte attenuator (BTLA) negatively regulates the immune response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients. BTLA expression in PBMCs and CD4(+) T cells was significantly decreased in active BD patients. Decreased BTLA level was associated with increased Th17 and Th1 responses. Activation of BTLA inhibited the abnormal Th17 and Th1 responses and IL-22 expression in both patients and controls. Addition of an agonistic anti-BTLA antibody remarkably inhibited DC-induced Th17 and Th1 cell responses, resulted in decreased production of the Th17 and Th1-related cytokines IL-1beta, IL-6, IL-23 and IL-12p70 and reduced CD40 expression in DCs. In conclusion, decreased BTLA expression in ocular BD may lead to inappropriate control of the Th17 and Th1 immune responses and DC functions. Therefore, BTLA may be involved in the development and recurrence of this disease. Agonistic agents of BTLA may represent a potential therapeutic approach for the treatment of BD and other inflammatory diseases mediated by abnormal Th17 and Th1 immune responses. PMID:26841832

  5. Immunity to experimental Salmonella typhimurium infections in rats. Transfer of immunity with primed CD4+CD25high and CD4+CD25low T lymphocytes

    DEFF Research Database (Denmark)

    Thygesen, P; Brandt, L; Jørgensen, T;

    1994-01-01

    The protective effect of primed CD4+ T lymphocytes against a lethal dose of 10(8) viable Salmonella typhimurium was studied in Lewis rats. Primed CD4+ T lymphocytes were obtained by inoculating Lewis rats with a non-lethal dose of 10(6) viable S. typhimurium. Four weeks after the infection, spleen...... fluorescence-activated cell sorter. Untreated Lewis rats were injected with 10(4) different primed CD4+ T-cell populations 24 h prior to the lethal dose of 10(8) viable S. typhimurium. Blood samples were drawn from the orbital plexus 1, 2, 3, and 4 weeks after the infection, and analysed for specific IgM and...... levels were not correlated with protection against S. typhimurium infections, although it showed that a higher and more persistent level of specific IgG antibodies was produced in animals receiving the CD4+CD25high fraction. It is concluded that 10(4) primed CD4+ T lymphocytes can induce immunity in...

  6. Astaxanthin, a Carotenoid, Stimulates Immune Responses by Enhancing IFN-γ and IL-2 Secretion in Primary Cultured Lymphocytes in Vitro and ex Vivo

    OpenAIRE

    Kuan-Hung Lin; Kao-Chang Lin; Wan-Jung Lu; Philip-Aloysius Thomas; Thanasekaran Jayakumar; Joen-Rong Sheu

    2015-01-01

    Astaxanthin, a potent antioxidant carotenoid, plays a major role in modulating the immune response. In this study, we examined the immunomodulatory effects of astaxanthin on cytokine production in primary cultured lymphocytes both in vitro and ex vivo. Direct administration of astaxanthin (70–300 nM) did not produce cytotoxicity in lipopolysaccharide (LPS, 100 µg/ mL)- or concanavalin A (Con A, 10 µg/ mL)-activated lymphocytes, whereas astaxanthin alone at 300 nM induced proliferation of sple...

  7. Experimental Salmonella typhimurium infections in rats. III. Transfer of immunity with primed lymphocyte subpopulations

    DEFF Research Database (Denmark)

    Hougen, H P; Jensen, E T

    1990-01-01

    The protective effect of primed lymphocytes against a lethal dose of Salmonella typhimurium was studied in athymic and euthymic LEW rats. Primed lymphocytes were obtained by inoculating euthymic and thymus-grafted animals with a non-lethal dose of Salmonella typhimurium. Four weeks after the...... athymic rats were injected with different doses of primed pan B, pan T, CD4+ and CD8+ T lymphocytes before inoculation with a lethal bacterial dose. Most of the animals treated with pan B, pan T or CD8+ cells died within two weeks. After treatment with primed CD4+ cells, only six of 39 animals died. Doses...... as low as 10(4) cells from both euthymic or thymus-grafted animals were effective, and athymic and euthymic recipients survived equally well. Four weeks after the infection both athymic and euthymic animals housed very few bacteria and had high antibacterial antibody titres. The percentages of...

  8. Immune regulatory cells and IL17-producing lymphocytes in patients with benign and malignant salivary gland tumors.

    Science.gov (United States)

    Haghshenas, Mohammad Reza; Khademi, Bijan; Faghih, Zahra; Ghaderi, Abbas; Erfani, Nasrollah

    2015-04-01

    The relationship between salivary gland tumors and immune system has not been well inspected. We aimed to investigate the distribution of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells, CTLA4(+)CD4(+) lymphocytes, as well asIL-17 producing CD4(+) and CD8(+) (Th17 and Tc17) lymphocytes in peripheral blood of patients with benign and malignant salivary gland tumors and a group of healthy controls. Peripheral blood samples were obtained from 27 patients with salivary gland tumors (19 benign and 8 malignant; mean age of 49.2±18.3), as well as19 age/sex matched healthy donors. Fluorochrome-conjugated antibodies were used to stain the cell surface markers, as well as intracellular molecules following cell-membrane fixation and permeabilization. The stained cells were acquired on a FACSCalibur four-color flowcytometer and analyzed by CellQuest Pro software package. The data were presented as mean percentages±SEM. Results indicated that the patients with malignant salivary gland tumors have increased percentage of Treg cells (7.74±1.1) and intracellular CTLA4 (inCTLA4)-positive CD4(+) lymphocytes (8.18±1.77) in comparison to the patients with benign tumors (4.38±0.56 for Treg cells and 3.83±0.56 for CTLA4(+)CD4(+) cells), as well as control subjects (2.34±0.28 for Treg cells and 2.22±0.25 for CTLA4(+)CD4(+) cells) (p≤0.001). Conversely these patients had reduced percentage of Th17 cells (0.84±0.14) comparing to the patients with benign tumors (2.09±0.31) as well as control subjects (2.31±0.23) (p≤0.001). In addition, the ratio of Th17/Treg lymphocytes was significantly lower in both malignant (0.12±0.03) and benign (0.48±0.09) tumors in comparison to control subjects (1.26±0.23) (pTc17 cells in patients with benign (1.14±0.15) and malignant (0.60±0.13) tumors was nearly similar to those in control subjects (0.83±0.14) but the mean expression intensityofIL-17 by these cells was significantly higher in patients with malignant tumors (11.06±1.26) than

  9. Indicators of allogenic interactions of lymphocytes in spouses as additional diagnostic and prognostic criteria of immune forms of reproductive failures

    Directory of Open Access Journals (Sweden)

    Belenkova O.V.

    2013-12-01

    Full Text Available Research objective: to search new laboratory approaches to the diagnostics of immune forms of reproductive failures. Materials and methods. Retrospective research a case — control of 54 married couples with idiopathic reproductive failures (in the anamnesis — 3 and more spontaneously interrupted pregnancy in the 4-8th weeks and 47 married couples having two and more children has been conducted. Results. It has been revealed that at the immune form of reproductive failures increase of cells of level A- mononuclear cells, expression of HLDR takes place that promotes tolerance cancellation to allogenic germs and to immune interruption of pregnancy. At reproductive failures female au-toserum positively influences activation of T-lymphocyte (CD3 +/HLADR + that may lead to the death of half- allogenic germ. Conclusion. Level of expression of CD3 and HLADR on CD45 + of mixed allogenic mononuclear cells of spouses may serve as a diagnostic significant criterion for revealing immune reasons of reproductive failures.

  10. A flagellin-derived toll-like receptor 5 agonist stimulates cytotoxic lymphocyte-mediated tumor immunity.

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    Nicholas D Leigh

    Full Text Available Toll-like receptor (TLR mediated recognition of pathogen associated molecular patterns allows the immune system to rapidly respond to a pathogenic insult. The "danger context" elicited by TLR agonists allows an initially non-immunogenic antigen to become immunogenic. This ability to alter environment is highly relevant in tumor immunity, since it is inherently difficult for the immune system to recognize host-derived tumors as immunogenic. However, immune cells may have encountered certain TLR ligands associated with tumor development, yet the endogenous stimulation is typically not sufficient to induce spontaneous tumor rejection. Of special interest are TLR5 agonists, because there are no endogenous ligands that bind TLR5. CBLB502 is a pharmacologically optimized TLR5 agonist derived from Salmonella enterica flagellin. We examined the effect of CBLB502 on tumor immunity using two syngeneic lymphoma models, both of which do not express TLR5, and thus do not directly respond to CBLB502. Upon challenge with the T-cell lymphoma RMAS, CBLB502 treatment after tumor inoculation protects C57BL/6 mice from death caused by tumor growth. This protective effect is both natural killer (NK cell- and perforin-dependent. In addition, CBLB502 stimulates clearance of the B-cell lymphoma A20 in BALB/c mice in a CD8(+ T cell-dependent fashion. Analysis on the cellular level via ImageStream flow cytometry reveals that CD11b(+ and CD11c(+ cells, but neither NK nor T cells, directly respond to CBLB502 as determined by NFκB nuclear translocation. Our findings demonstrate that CBLB502 stimulates a robust antitumor response by directly activating TLR5-expressing accessory immune cells, which in turn activate cytotoxic lymphocytes.

  11. Astaxanthin, a Carotenoid, Stimulates Immune Responses by Enhancing IFN-γ and IL-2 Secretion in Primary Cultured Lymphocytes in Vitro and ex Vivo.

    Science.gov (United States)

    Lin, Kuan-Hung; Lin, Kao-Chang; Lu, Wan-Jung; Thomas, Philip-Aloysius; Jayakumar, Thanasekaran; Sheu, Joen-Rong

    2016-01-01

    Astaxanthin, a potent antioxidant carotenoid, plays a major role in modulating the immune response. In this study, we examined the immunomodulatory effects of astaxanthin on cytokine production in primary cultured lymphocytes both in vitro and ex vivo. Direct administration of astaxanthin (70-300 nM) did not produce cytotoxicity in lipopolysaccharide (LPS, 100 µg/ mL)- or concanavalin A (Con A, 10 µg/ mL)-activated lymphocytes, whereas astaxanthin alone at 300 nM induced proliferation of splenic lymphocytes (p astaxanthin, alone or with Con A, had no apparent effect on interferon (INF-γ) and interleukin (IL-2) production in primary cultured lymphocytes, it enhanced LPS-induced INF-γ production. In an ex vivo experiment, oral administration of astaxanthin (0.28, 1.4 and 7 mg/kg/day) for 14 days did not cause alterations in the body or spleen weights of mice and also was not toxic to lymphocyte cells derived from the mice. Moreover, treatment with astaxanthin significantly increased LPS-induced lymphocyte proliferation ex vivo but not Con A-stimulated lymphocyte proliferation ex vivo. Enzyme linked immunosorbent assay (ELISA) analysis revealed that administration of astaxanthin significantly enhanced INF-γ production in response to both LPS and Con A stimulation, whereas IL-2 production increased only in response to Con A stimulation. Also, astaxanthin treatment alone significantly increased IL-2 production in lymphocytes derived from mice, but did not significantly change production of INF-γ. These findings suggest that astaxanthin modulates lymphocytic immune responses in vitro, and that it partly exerts its ex vivo immunomodulatory effects by increasing INF-γ and IL-2 production without inducing cytotoxicity. PMID:26729100

  12. Astaxanthin, a Carotenoid, Stimulates Immune Responses by Enhancing IFN-γ and IL-2 Secretion in Primary Cultured Lymphocytes in Vitro and ex Vivo

    Directory of Open Access Journals (Sweden)

    Kuan-Hung Lin

    2015-12-01

    Full Text Available Astaxanthin, a potent antioxidant carotenoid, plays a major role in modulating the immune response. In this study, we examined the immunomodulatory effects of astaxanthin on cytokine production in primary cultured lymphocytes both in vitro and ex vivo. Direct administration of astaxanthin (70–300 nM did not produce cytotoxicity in lipopolysaccharide (LPS, 100 µg/ mL- or concanavalin A (Con A, 10 µg/ mL-activated lymphocytes, whereas astaxanthin alone at 300 nM induced proliferation of splenic lymphocytes (p < 0.05 in vitro. Although astaxanthin, alone or with Con A, had no apparent effect on interferon (INF-γ and interleukin (IL-2 production in primary cultured lymphocytes, it enhanced LPS-induced INF-γ production. In an ex vivo experiment, oral administration of astaxanthin (0.28, 1.4 and 7 mg/kg/day for 14 days did not cause alterations in the body or spleen weights of mice and also was not toxic to lymphocyte cells derived from the mice. Moreover, treatment with astaxanthin significantly increased LPS-induced lymphocyte proliferation ex vivo but not Con A-stimulated lymphocyte proliferation ex vivo. Enzyme linked immunosorbent assay (ELISA analysis revealed that administration of astaxanthin significantly enhanced INF-γ production in response to both LPS and Con A stimulation, whereas IL-2 production increased only in response to Con A stimulation. Also, astaxanthin treatment alone significantly increased IL-2 production in lymphocytes derived from mice, but did not significantly change production of INF-γ. These findings suggest that astaxanthin modulates lymphocytic immune responses in vitro, and that it partly exerts its ex vivo immunomodulatory effects by increasing INF-γ and IL-2 production without inducing cytotoxicity.

  13. Antibody responses to vaccination and immune function in patients with haematological malignancies - studies in patients with chronic lymphocytic leukaemia autologous stem cell recipients

    OpenAIRE

    Velden, A.M.T. van der

    2007-01-01

    This thesis concerns the antibody responses to vaccination and immune function of patients with several forms of haematological diseases. Antibody responses in patients with chronic lymphocytic leukaemia (CLL) and in autologous stem cell transplant recipients were studied. In the autologous stem cell transplantation (aSCT) group, immune reconstitution after aSCT was analysed in detail during 15 months following transplantation. The first part of the thesis concerns patients with chronic lymph...

  14. Influence of prevaccination immunity on the human B-lymphocyte response to a Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Kristensen, K; Henrichsen, J;

    1991-01-01

    The purpose of this study was to investigate whether preexisting immunity to components of a polysaccharide-protein conjugate influences the B-lymphocyte response to vaccination with the conjugate. Thirty-two healthy adults were vaccinated once or twice with a conjugate (PRP-D) consisting of...... Haemophilus influenzae type b capsular polysaccharide (PRP) and diphtheria toxoid (DT), and the response was related to the prevaccination levels of PRP and DT antibodies. Positive correlations were found between increases in plasma PRP (median, 32.0 micrograms/ml) and DT (1.14 IU/ml) antibodies and numbers...... of circulating PRP and DT antibody-secreting cells (AbSC) (postvaccination days 6 to 9). The B-cell responses (antibody response and AbSC) to both PRP and DT correlated positively with prevaccination levels of anti-DT. DT AbSC appeared earlier (peak, day 7) than PRP AbSC (peak, day 8). Individuals...

  15. Immune-mediated adverse events of anticytotoxic T lymphocyte-associated antigen 4 antibody therapy in metastatic melanoma.

    Science.gov (United States)

    Quirk, Shannon K; Shure, Anna K; Agrawal, Devendra K

    2015-11-01

    Ipilimumab, an antibody that blocks cytotoxic T lymphocyte-associated antigen 4 (CTLA-4; CD152), was approved by the Food and Drug Administration in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular effects, renal effects, neurologic effects, and others. In this article, a critical evaluation of the underlying mechanisms of irAEs associated with anti-CTLA-4 therapy is presented. Additionally, potentially beneficial effects of combinational therapies to alleviate ipilimumab-induced irAEs in malignant melanoma are discussed. Future research is warranted to elucidate the efficacy of such combination therapies and specific biomarkers that would help to predict a clinical response to ipilimumab in patients with malignant melanoma. PMID:26118951

  16. Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity.

    Science.gov (United States)

    Lampson, Benjamin L; Kasar, Siddha N; Matos, Tiago R; Morgan, Elizabeth A; Rassenti, Laura; Davids, Matthew S; Fisher, David C; Freedman, Arnold S; Jacobson, Caron A; Armand, Philippe; Abramson, Jeremy S; Arnason, Jon E; Kipps, Thomas J; Fein, Joshua; Fernandes, Stacey; Hanna, John; Ritz, Jerome; Kim, Haesook T; Brown, Jennifer R

    2016-07-14

    Idelalisib is a small-molecule inhibitor of PI3Kδ with demonstrated efficacy for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as front-line therapy, we enrolled 24 subjects in a phase 2 study consisting of 2 months of idelalisib monotherapy followed by 6 months of combination therapy with idelalisib and the anti-CD20 antibody ofatumumab. After a median follow-up period of 14.7 months, hepatotoxicity was found to be a frequent and often severe adverse event. A total of 19 subjects (79%) experienced either grade ≥1 ALT or AST elevation during the study, and 13 subjects (54%) experienced grade ≥3 transaminitis. The median time to development of transaminitis was 28 days, occurring before ofatumumab introduction. Younger age and mutated immunoglobulin heavy chain status were significant risk factors for the development of hepatotoxicity. Multiple lines of evidence suggest that this hepatotoxicity was immune mediated. A lymphocytic infiltrate was seen on liver biopsy specimens taken from 2 subjects with transaminitis, and levels of the proinflammatory cytokines CCL-3 and CCL-4 were higher in subjects experiencing hepatotoxicity. All cases of transaminitis resolved either by holding the drug, initiating immunosuppressants, or both, and rates of recurrent toxicity were lower in patients taking steroids when idelalisib was reinitiated. A decrease in peripheral blood regulatory T cells was seen in patients experiencing toxicity on therapy, which is consistent with an immune-mediated mechanism. These results suggest that caution should be taken as drugs within this class are developed for CLL, particularly in younger patients who have not received prior disease-specific therapy. This study was registered at www.clinicaltrials.gov as #NCT02135133. PMID:27247136

  17. Immune responses to recombinant hepatitis B virus vaccine in human immunodeficiency virus-1-infected patients with different CD4~+ T-lymphocyte

    Institute of Scientific and Technical Information of China (English)

    蔡琳

    2014-01-01

    Objective.To compare the difference of immune responses to hepatitis B virus(HBV)vaccine in human immunodeficiency virus(HIV)-1-infected patients with different CD4+T-lymphocyte counts.Methods HIV-1 infected patients who visited clinic at the Public Health Clinical Center of Chengdu were enrolled and divided in-+

  18. Native and recombinant herpes simplex virus type 1 envelope proteins induce human immune T-lymphocyte responses.

    Science.gov (United States)

    Torseth, J W; Cohen, G H; Eisenberg, R J; Berman, P W; Lasky, L A; Cerini, C P; Heilman, C J; Kerwar, S; Merigan, T C

    1987-05-01

    The abilities of whole herpes simplex virus type 1 (HSV-1) antigen (HSV-ag) and purified HSV-1 native and recombinant envelope proteins to stimulate in vitro T-lymphocyte responses were compared in patients with recurrent herpes labialis. Immunochemically purified preparations of native glycoproteins B, C, and D (ngB, ngC, ngD) from cultured HSV-1 as well as expressed recombinant plasmid preparations of gD (rgD-1t, rgD-45K) elicited lymphocyte proliferation (LT) and production of gamma interferon (IFN-gamma) and interleukin-2 (IL-2) only in seropositive individuals. The IFN-gamma induced by rgD-1t correlated with the time to the next herpetic lesion in 19 volunteers followed to recurrence (r = 0.69, P less than 0.008), although the magnitude and frequency of LT and IFN-gamma responses were lower with either recombinant or native purified antigens than with the whole-virus antigen. Combinations of ngB plus ngD or ngB plus ngC plus ngD stimulated more IFN-gamma, equivalent to whole-virus-antigen responses. Recombinant-derived human IL-2 also specifically increased LT and IFN-gamma responses in antigen-driven cultures. ngD stimulated IL-2 and LT responses similar to those of whole-virus antigen and higher than those of ngC. HSV-ag and ngB induced significantly higher titers of total IFN than could be accounted for by IFN-gamma; this was not seen for the other antigens, which induced only IFN-gamma. HSV-ag-driven Leu 2a-, plastic-nonadherent blood cells, unlike whole peripheral blood mononuclear cells, showed evidence of an increase and then a decline in the frequency of HSV-responsive cells after a lesion recurrence. These studies suggest that HSV-1 envelope proteins are capable of stimulating an immune T-helper-cell response which is associated with the prevention of human herpes simplex lesion recurrence. Although the whole virus probably contains additional important antigens, increasing concentrations or combinations of certain purified glycoproteins or the

  19. Peptide vaccination induces profound changes in the immune system in patients with B-cell chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Michael Schmitt

    2011-04-01

    Full Text Available Although the immune status of chronic lymphocytic leukemia (CLL patients is mostly characterized by immunosuppression, there is an accumulation of in vivo (graft-versus-leukemia effect and in vitro (spontaneous remissions after infections data that indicates that CLL might be effectively targeted by T-cell based immunotherapy. Recently, we characterized receptor for hyaluronic acid mediated motility (RHAMM as a preferential target for immunotherapy of CLL. We also completed a RHAMM-derived peptide vaccination phase I/II clinical trial in CLL. Here, we present a detailed immunological analysis of six CLL patients vaccinated with HLA-A2 restricted RHAMM-derived epitope R3 (ILSLELMKL. Beside effective induction of R3-specific cytotoxic T-cells, peptide vaccination caused profound changes in different T-cell subsets as well as cytokines. We present longitudinal analyses of Th17, CD8+CD103+, CD8+CD137+ and IL-17 producing CD8+ T cells (CD8+IL- -17+ as well as important cytokines involved in regulation of immune response such as TGF-β, IL-10, IL-2 and TNF throughout the peptide vaccination period. (Folia Histochemica et Cytobiologica 2011, Vol. 49, No. 1, 161–167

  20. Management of granulomatous lymphocytic interstitial lung disease in a patient with common variable immune deficiency.

    Science.gov (United States)

    Pathria, Mohini; Urbine, Daniel; Zumberg, Marc Stuart; Guarderas, Juan

    2016-01-01

    A 61-year-old woman presented with longstanding cough and progressive dyspnoea. She underwent an extensive evaluation and was diagnosed with common variable immunodeficiency (CVID) with granulomatous lymphocytic interstitial lung disease (GLILD). She was initially treated with subcutaneous immunoglobulin therapy, having declined intravenous immunoglobulin (IVIG) therapy. She also declined treatment with oral glucocorticoids. Over several months, she became increasingly symptomatic and developed increased pulmonary infiltrates, pleural effusions, mediastinal adenopathy, splenomegaly, pancytopenia and ascites. An interdisciplinary team composed of an immunologist, pulmonologist and haematologist deliberated over a therapeutic management approach. The patient received a recently reported immunotherapy regimen with azathioprine and rituximab. The therapy led to rapid improvement of her constitutional and respiratory symptoms, with clinical and radiographic improvement in her interstitial lung disease, lymphadenopathy, pleural effusions and ascites. This case report reviews the literature surrounding the diagnosis and management of GLILD. PMID:27335365

  1. Immunization with a single major histocompatibility complex class I-restricted cytotoxic T-lymphocyte recognition epitope of herpes simplex virus type 2 confers protective immunity.

    Science.gov (United States)

    Blaney, J E; Nobusawa, E; Brehm, M A; Bonneau, R H; Mylin, L M; Fu, T M; Kawaoka, Y; Tevethia, S S

    1998-12-01

    We have evaluated the potential of conferring protective immunity to herpes simplex virus type 2 (HSV-2) by selectively inducing an HSV-specific CD8(+) cytotoxic T-lymphocyte (CTL) response directed against a single major histocompatibility complex class I-restricted CTL recognition epitope. We generated a recombinant vaccinia virus (rVV-ES-gB498-505) which expresses the H-2Kb-restricted, HSV-1/2-cross-reactive CTL recognition epitope, HSV glycoprotein B residues 498 to 505 (SSIEFARL) (gB498-505), fused to the adenovirus type 5 E3/19K endoplasmic reticulum insertion sequence (ES). Mucosal immunization of C57BL/6 mice with this recombinant vaccinia virus induced both a primary CTL response in the draining lymph nodes and a splenic memory CTL response directed against HSV gB498-505. To determine the ability of the gB498-505-specific memory CTL response to provide protection from HSV infection, immunized mice were challenged with a lethal dose of HSV-2 strain 186 by the intranasal (i.n.) route. Development of the gB498-505-specific CTL response conferred resistance in 60 to 75% of mice challenged with a lethal dose of HSV-2 and significantly reduced the levels of infectious virus in the brains and trigeminal ganglia of challenged mice. Finally, i.n. immunization of C57BL/6 mice with either a recombinant influenza virus or a recombinant vaccinia virus expressing HSV gB498-505 without the ES was also demonstrated to induce an HSV-specific CTL response and provide protection from HSV infection. This finding confirms that the induction of an HSV-specific CTL response directed against a single epitope is sufficient for conferring protective immunity to HSV. Our findings support the role of CD8(+) T cells in the control of HSV infection of the central nervous system and suggest the potential importance of eliciting HSV-specific mucosal CD8(+) CTL in HSV vaccine design. PMID:9811690

  2. The influence of different micro-injury interventional treatment on the T lymphocyte immune function in patients with primary hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Objective: To investigate the influence of different micro-injury interventional treatments on the T lymphocyte immune function in patients with primary hepatocellular carcinoma (HCC). Methods: A total of 50 patients with pathologically - proved HCC were enrolled in this study. Transcatheter arterial chemoembolization (TACE) was carried out in 31 patients, while radiofrequency ablation (RFA) was performed in 19 patients. According to the tumor's diameter, the patients were divided into small HCC group (≤5 cm) and larger HCC group (>5 cm). Peripheral blood was taken before and one, seven days after the treatment to determine CD3, CD4, CD8 as well as the ratio of CD4/CD8 using flow cytometry, assay. The results were analyzed. Results: One day after either TACE or RFA treatment in small HCC group, T lymphocytes in peripheral blood, including CD3, CD4, CD8 as well as the ratio of CD4/CD8, were kept at the same levels as before. However, seven days after the treatment T lymphocytes (including CD3, CD4, CD8 as well as the ratio of CD4/CD8) were significantly increased in RFA group, while T lymphocytes were obviously decreases in TACE group. One day after either TACE or RFA treatment in larger HCC group, T lymphocytes showed a remarkable decrease in both groups (P<0.05), while seven days after the treatment T lymphocytes and the ratio of CD4/CD8 increased significantly, especially in RFA group. Conclusion: The different micro-injury interventional treatments carry different influences on the T lymphocyte immune function in patients with primary hepatocellular carcinoma, which may be related to the size of tumor. (authors)

  3. Localization of alpha/beta and gamma/delta T lymphocytes in Cryptosporidium parvum-infected tissues in naive and immune calves.

    OpenAIRE

    Abrahamsen, M S; Lancto, C A; Walcheck, B; Layton, W.; Jutila, M A

    1997-01-01

    The nature of the host's T-lymphocyte population within the intestinal villi following Cryptosporidium parvum infection was characterized with a bovine model of cryptosporidiosis. In naive animals, infection with C. parvum resulted in substantial increases in the numbers of alpha/beta T cells, both CD4+ (150%) and CD8+ (60%), and of gamma/delta T cells (70%) present within the intestinal villi of the infected ileum. In immune animals, the host T-lymphocyte response to a challenge infection wi...

  4. Protective CD8+ T lymphocytes in Primates Immunized with Malaria Sporozoites

    OpenAIRE

    Weiss, Walter R.; Jiang, Chengyong George

    2012-01-01

    Live attenuated malaria vaccines are more potent than the recombinant protein, bacterial or viral platform vaccines that have been tested, and an attenuated sporozoite vaccine against falciparum malaria is being developed for humans. In mice, attenuated malaria sporozoite vaccines induce CD8+ T cells that kill parasites developing in the liver. We were curious to know if CD8+ T cells were also important in protecting primates against malaria. We immunized 9 rhesus monkeys with radiation atten...

  5. KIR and HLA Genotypes Implicated in Reduced Killer Lymphocytes Immunity Are Associated with Vogt-Koyanagi-Harada Disease.

    Science.gov (United States)

    Levinson, Ralph D; Yung, Madeline; Meguro, Akira; Ashouri, Elham; Yu, Fei; Mizuki, Nobuhisa; Ohno, Shigeaki; Rajalingam, Raja

    2016-01-01

    Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher's exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral

  6. KIR and HLA Genotypes Implicated in Reduced Killer Lymphocytes Immunity Are Associated with Vogt-Koyanagi-Harada Disease

    Science.gov (United States)

    Levinson, Ralph D.; Yung, Madeline; Meguro, Akira; Ashouri, Elham; Yu, Fei; Mizuki, Nobuhisa; Ohno, Shigeaki

    2016-01-01

    Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are killer lymphocytes that provide defense against viral infections and tumor transformation. Analogous to that of CTL, interactions of killer-cell immunoglobulin-like receptors (KIR) with specific human leukocyte antigen (HLA) class I ligands calibrate NK cell education and response. Gene families encoding KIRs and HLA ligands are located on different chromosomes, and feature variation in the number and type of genes. The independent segregation of KIR and HLA genes results in variable KIR-HLA interactions in individuals, which may impact disease susceptibility. We tested whether KIR-HLA combinations are associated with Vogt-Koyanagi-Harada (VKH) disease, a bilateral granulomatous panuveitis that has strong association with HLA-DR4. We present a case control study of 196 VKH patients and 209 controls from a highly homogeneous native population of Japan. KIR and HLA class I genes were typed using oligonucleotide hybridization method and analyzed using two-tailed Fisher’s exact probabilities. The incidence of Bx-KIR genotypes was decreased in VKH patients (odds ratio [OR] 0.58, P = 0.007), due primarily to a decrease in centromeric B-KIR motif and its associated KIRs 2DS2, 2DL2, 2DS3, and 2DL5B. HLA-B22, implicated in poor immune response, was increased in VKH (OR = 4.25, P = 0.0001). HLA-Bw4, the ligand for KIR3DL1, was decreased in VKH (OR = 0.59, P = 0.01). The KIR-HLA combinations 2DL2+C1/C2 and 3DL1+Bw4, which function in NK education, were also decreased in VKH (OR = 0.49, P = 0.012; OR = 0.59, P = 0.013). Genotypes missing these two inhibitory KIR-HLA combinations in addition to missing activating KIRs 2DS2 and 2DS3 were more common in VKH (OR = 1.90, P = 0.002). These results suggest that synergistic hyporesponsiveness of NK cells (due to poor NK education along with missing of activating KIRs) and CTL (due to HLA-B22 restriction) fail to mount an effective immune response against viral

  7. Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress

    International Nuclear Information System (INIS)

    Highlights: • Sublethal brevetoxin exposure affects manatee immune function. • Plasma brevetoxin levels correlate with oxidative stress in rescued manatees. • Brevetoxin exposure affects lymphocyte proliferation in rescued manatees. • Plasma brevetoxin concentrations ranged from 0 to 19 ng PbTx-3 eq/mL. - Abstract: The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida’s southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (p < 0.05) in lymphocyte proliferation were observed in ConA and PHA stimulated lymphocytes from rescued animals compared to non-exposed animals. Significant correlations were observed between oxidative stress markers (SOD, ROS/RNS) and plasma brevetoxin concentrations. Sublethal exposure to brevetoxins in the

  8. Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Catherine J., E-mail: cjwalsh@mote.org [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Butawan, Matthew, E-mail: mattbutawan@outlook.com [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Yordy, Jennifer, E-mail: jennifer.e.balmer@gmail.com [Marine Immunology Program, Mote Marine Laboratory, 1600 Ken Thompson Parkway, Sarasota, FL 34236 (United States); Ball, Ray, E-mail: Ray.Ball@lowryparkzoo.com [Lowry Park Zoo, 1101 W Sligh Ave, Tampa, FL 33604 (United States); Flewelling, Leanne, E-mail: Leanne.Flewelling@MyFWC.com [Fish and Wildlife Research Institute, Florida Fish and Wildlife Conservation Commission, 100 8th Ave SE, St. Petersburg, FL 33701 (United States); Wit, Martine de, E-mail: Martine.deWit@MyFWC.com [Fish and Wildlife Research Institute, Florida Fish and Wildlife Conservation Commission, 100 8th Ave SE, St. Petersburg, FL 33701 (United States); Bonde, Robert K., E-mail: rbonde@usgs.gov [U.S. Geological Survey, Sirenia Project, 7920 NE 71st Street, Gainesville, FL 32653 (United States)

    2015-04-15

    Highlights: • Sublethal brevetoxin exposure affects manatee immune function. • Plasma brevetoxin levels correlate with oxidative stress in rescued manatees. • Brevetoxin exposure affects lymphocyte proliferation in rescued manatees. • Plasma brevetoxin concentrations ranged from 0 to 19 ng PbTx-3 eq/mL. - Abstract: The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida’s southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (p < 0.05) in lymphocyte proliferation were observed in ConA and PHA stimulated lymphocytes from rescued animals compared to non-exposed animals. Significant correlations were observed between oxidative stress markers (SOD, ROS/RNS) and plasma brevetoxin concentrations. Sublethal exposure to brevetoxins in the

  9. Detailing profiles of Lawsonia intracellularis specific lymphocytes in the immune response to a challenge inoculation after oral vaccination or primary inoculation with virulent bacteria

    DEFF Research Database (Denmark)

    Riber, Ulla; Hvass, Henriette Cordes; Heegaard, Peter M. H.; Ståhl, Marie; Jensen, Tim Kåre; Jungersen, Gregers

    2012-01-01

    not induce measurable primary humoral or cell-mediated immune responses, nor was it able to reduce faecal shedding of bacteria from eight vaccinated pigs compared to seven age-matched naïve challenge-control pigs. Vaccinated pigs did, however, respond to vaccination with an acute phase protein...... IFN-γ producing cells in the vaccinated pigs showed profiles primarily of CD8+(CD4neg) and CD4+CD8+ double positive lymphocytes. Similar profiles of IFN-γ producing cells were found in re-inoculated immune pigs, which experienced a boost in CMI responses. Cellular proliferation was identified in...

  10. Th17/IL-17A might play a protective role in chronic lymphocytic leukemia immunity.

    Directory of Open Access Journals (Sweden)

    Iwona Hus

    Full Text Available Th17 cells, a recently discovered subset of T helper cells that secrete IL-17A, can affect the inflammation process autoimmune and cancer diseases development. The purpose of this study was to evaluate the role of Th17 cells and IL17A in biology of CLL. The study group included 294 untreated CLL patients in different clinical stages. Here, we show that higher Th17 and IL-17A values were associated with less advanced clinical stage of CLL. Th17 cells' percentages in PB were lower in patients who died due to CLL during follow-up due to CLL (as compared to surviving patients and in patients responding to first-line therapy with fludarabine-based regimens (as compared to non-responders. IL-17A inversely correlated with the time from CLL diagnosis to the start of therapy and was lower in patients who required treatment during follow-up. Th-17 and IL-17A values were lower in patients with adverse prognostic factors (17p and 11q deletion, CD38 and ZAP-70 expression. CLL patients with detectable IL-17A mRNA in T cells were in Rai Stage 0 and negative for both ZAP-70 and CD38 expression. Th17 percentages positively correlated with iNKT and adversely with Treg cells. The results of this study suggest that Th17 may play a beneficial role in CLL immunity.

  11. The absolute lymphocyte count accurately estimates CD4 counts in HIV-infected adults with virologic suppression and immune reconstitution

    Directory of Open Access Journals (Sweden)

    Barnaby Young

    2014-11-01

    Full Text Available Introduction: The clinical value of monitoring CD4 counts in immune reconstituted, virologically suppressed HIV-infected patients is limited. We investigated if absolute lymphocyte counts (ALC from an automated blood counting machine could accurately estimate CD4 counts. Materials and Methods: CD4 counts, ALC and HIV viral load (VL were extracted from an electronic laboratory database for all patients in HIV care at the Communicable Diseases Centre, Tan Tock Seng Hospital, Singapore (2008–13. Virologic suppression was defined as consecutive HIV VLs 300 cells/mm3. CD4 counts were estimated using the CD4% from the first value >300 and an ALC 181–540 days later. Results: A total of 1215 periods of virologic suppression were identified from 1183 patients, with 2227 paired CD4-ALCs available for analysis. 98.3% of CD4 estimates were within 50% of the actual value. 83.3% within 25% and 40.5% within 10%. The error pattern was approximately symmetrically distributed around a mean of −6.5%, but significant peaked and with mild positive skew (kurtosis 4.45, skewness 1.07. Causes for these errors were explored. Variability between lymphocyte counts measured by ALC and flow cytometry did not follow an apparent pattern, and contributed to 32% of the total error (median absolute error 5.5%, IQR 2.6–9.3. The CD4% estimate was significantly lower than the actual value (t-test, p<0.0001. The magnitude of this difference was greater for lower values, and above 25%, there was no significant difference. Precision of the CD4 estimate was similar as baseline CD4% increased, however accuracy improved significantly: from a median 16% underestimation to 0% as baseline CD4% increased from 12 to 30. Above a CD4% baseline of 25, estimates of CD4 were within 25% of the actual value 90.2% of the time with a median 2% underestimation. A robust (bisqaure linear regression model was developed to correct for the rise in CD4% with time, when baseline was 14–24

  12. Induction of novel CD8+ T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes

    DEFF Research Database (Denmark)

    Kloverpris, Henrik; Karlsson, Ingrid; Bonde, Jesper;

    2009-01-01

    OBJECTIVE:: To investigate the potential to induce additional cytotoxic T-lymphocyte (CTL) immunity during chronic HIV-1 infection. DESIGN:: We selected infrequently targeted or subdominant but conserved HLA-A*0201-binding epitopes in Gag, Pol, Env, Vpu and Vif. These relatively immune silent epi...... lead to stronger and more durable cellular responses to selected epitopes with the potential to control viral replication and prevent disease in HIV-1-infected individuals.......OBJECTIVE:: To investigate the potential to induce additional cytotoxic T-lymphocyte (CTL) immunity during chronic HIV-1 infection. DESIGN:: We selected infrequently targeted or subdominant but conserved HLA-A*0201-binding epitopes in Gag, Pol, Env, Vpu and Vif. These relatively immune silent...... epitopes were modified as anchor-optimized peptides to improve immunogenicity and delivered on autologous monocyte-derived dendritic cells (MDDCs). METHODS:: Twelve treatment-naïve HLA-A*0201 HIV-1-infected Danish individuals received 1 x 10 MDDCs subcutaneously (s.c.) (weeks 0, 2, 4 and 8), pulsed with...

  13. The potential impact of low dose ionizing γ-radiation on immune response activity up-regulated by Ikaros in IM-9 B lymphocytes

    International Nuclear Information System (INIS)

    The biological effects of low dose ionizing radiation (LDIR) remain insufficiently understood. We examined for the scientific evidence to show the biological effects of LDIR using radiation-sensitive immune cells. We found that Ikaros protein was responded to low dose-dependent effects of gamma radiation in IM-9 B lymphocytes. Ikaros encodes zinc finger transcription factors that is important regulators of a hematopoietic stem cells (HSCs) progression to the B lymphoid lineage development, differentiation and proliferation. In this study, we observed that cell proliferation was enhanced from 10% to 20% by LDIR (0.05 Gy) in IM-9 B lymphocytes. The Ikaros protein was phosphorylated in its serine/threonine (S/T) region and decreased its DNA binding activity in the cells exposed to LDIR. We found that Ikaros phosphorylation was up-regulated by CK2/AKT pathway and the residues of ser-304 and ser-306 in Ikaros was phosphorylated by LDIR. We also observed that Ikaros protein was localized from the nucleus to the cytoplasm after LDIR and bound with Autotaxin (ENPP2, ATX) protein, stimulating proliferation, migration and survival of immune cells. In addition, we found that the lysoPLD activity of ATX was dependent on Ikaros-ATX binding activity. These results indicate that the Ikaros is an important regulator of immune activation. Therefore, we suggest that low dose ionizing radiation can be considered as a beneficial effects, stimulating the activation of immune cells.

  14. Immunization with antigenic peptides complexed with β-glucan induces potent cytotoxic T-lymphocyte activity in combination with CpG-ODNs.

    Science.gov (United States)

    Mochizuki, Shinichi; Morishita, Hiromi; Kobiyama, Kouji; Aoshi, Taiki; Ishii, Ken J; Sakurai, Kazuo

    2015-12-28

    The induction of antigen-specific immune responses requires immunization with not only antigens, but also adjuvants. CpG oligonucleotides (CpG-ODNs) are well-known ligands for Toll-like receptor 9 and a potent adjuvant that induces both Th1-type humoral and cellular immune responses including cytotoxic T-lymphocyte responses. We previously demonstrated that β-glucan schizophyllan (SPG) can form complexes with CpG-ODNs with attached dA40 (CpG-dA/SPG), which can accumulate in macrophages in the draining inguinal lymph nodes and induce strong immune responses by co-administration of antigenic proteins, namely ovalbumin (OVA). Immunization with antigenic peptides, OVA257-264, did not induce these antigen-specific immune responses even in combination with CpG-dA/SPG, indicating that peptides require a carrier to antigen presenting cells. In this study, we prepared conjugates comprising OVA257-264 and dA40, and made complexes with SPG. Immunization with OVA257-264-dA/SPG induced peptide-specific immune responses in combination with CpG-dA regardless of complexation with SPG both in vitro and in vivo. When splenocytes from immunized mice were incubated with E.G7-OVA tumor model cells presenting OVA peptides, the number of cells drastically decreased after 24h. Furthermore, mice pre-immunized with OVA257-264-dA/SPG and CpG-ODNs exhibited a long delay in tumor growth after tumor inoculation. Therefore, these peptide-dA/SPG and CpG-dA/SPG complexes could be used as a potent vaccine for the treatment of cancers and infectious diseases. PMID:26562685

  15. Effects of tumor-like assay conditions, ionizing radiation, and hyperthermia on immune lysis of tumor cells by cytotoxic T-lymphocytes

    International Nuclear Information System (INIS)

    Cytotoxic T-lymphocytes (CTL's) harvested from mixed splenic lymphocyte cultures (DBA/2 + C57BL) were tested for their ability to lyse allogeneic P815 mastocytoma cells under various tumor-like assay conditions, with or without previous exposure to ionizing radiation or hyperthermia (430). There was little or no decrease of immune cytolysis when CTL's were assayed by 51Cr release under tumor-like conditions (plateau-phase target cells, low pH, or anoxia) or after irradiation, but cytolytic activity was greatly reduced when CTL's were exposed to heat; 45 min of hyperthermic treatment decreased activity by greater than or equal to 99 percent while reducing the apparent cell viability (as indicated by trypan blue exclusion) by only 30 percent. When the P815 target cells rather than the CTL's were exposed to heat, their susceptibility to immune lysis was not affected even after treatment times that were lethal to the tumor cells. Despite the dissimilar heat sensitivities of CTL and P815 cells, the dose-response curves for inhibition of protein synthesis by heat, as indicated by [3H]leucine incorporation, were similar for both cell types; neither the depression of protein synthesis in heated CTL's nor the decreased cytolytic ability of these cells was reversed within 3 hr. When irradiated or heated 2815 cells were incubated with CTL's, the resulting survival curves were always additive, indicating that neither irradiation nor heat treatment affected the susceptibility of the tumor cells to immune attack. The extreme heat sensitivity of cytotoxic T-lymphocytes raises important questions about the possible effects of hyperthermic treatment on the immune competence of cancer patients

  16. Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress.

    Science.gov (United States)

    Walsh, Catherine J; Butawan, Matthew; Yordy, Jennifer; Ball, Ray; Flewelling, Leanne; de Wit, Martine; Bonde, Robert K

    2015-04-01

    The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida's southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (p<0.05) in lymphocyte proliferation were observed in ConA and PHA stimulated lymphocytes from rescued animals compared to non-exposed animals. Significant correlations were observed between oxidative stress markers (SOD, ROS/RNS) and plasma brevetoxin concentrations. Sublethal exposure to brevetoxins in the wild impacts some immune function components, and thus, overall health, in the Florida manatee. PMID:25678466

  17. The route of immunization with adenoviral vaccine influences the recruitment of cytotoxic T lymphocytes in the lung that provide potent protection from influenza A virus.

    Science.gov (United States)

    Suda, Tatsuya; Kawano, Masaaki; Nogi, Yasuhisa; Ohno, Naohito; Akatsuka, Toshitaka; Matsui, Masanori

    2011-09-01

    Virus-specific cytotoxic T lymphocytes (CTLs) in the lung are considered to confer protection from respiratory viruses. Several groups demonstrated that the route of priming was likely to have an implication for the trafficking of antigen-specific CTLs. Therefore, we investigated whether the route of immunization with adenoviral vaccine influenced the recruitment of virus-specific CTLs in the lung that should provide potent protection from influenza A virus. Mice were immunized with recombinant adenovirus expressing the matrix (M1) protein of influenza A virus via various immunization routes involving intraperitoneal, intranasal, intramuscular, or intravenous administration as well as subcutaneous administration in the hind hock. We found that the immunization route dramatically impacted the recruitment of M1-specific IFN-γ(+) CD8(+) T cells both in the lung and the spleen. Surprisingly, hock immunization was most effective for the accumulation in the lung of IFN-γ-producing CD8(+) T cells that possessed M1-specific cytolytic activity. Further, antigen-driven IFN-γ(+) CD8(+) T cells in the lung, but not in the spleen, were likely to be correlated with the resistance to challenge with influenza A virus. These results may improve our ability to design vaccines that target virus-specific CTL responses to respiratory viruses such as influenza A virus. PMID:21722671

  18. Decreased B and T lymphocyte attenuator in Behcet’s disease may trigger abnormal Th17 and Th1 immune responses

    Science.gov (United States)

    Ye, Zi; Deng, Bolin; Wang, Chaokui; Zhang, Dike; Kijlstra, Aize; Yang, Peizeng

    2016-01-01

    Behcet’s disease (BD) is a chronic, systemic and recurrent inflammatory disease associated with hyperactive Th17 and Th1 immune responses. Recent studies have shown that B and T lymphocyte attenuator (BTLA) negatively regulates the immune response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients. BTLA expression in PBMCs and CD4+ T cells was significantly decreased in active BD patients. Decreased BTLA level was associated with increased Th17 and Th1 responses. Activation of BTLA inhibited the abnormal Th17 and Th1 responses and IL-22 expression in both patients and controls. Addition of an agonistic anti-BTLA antibody remarkably inhibited DC-induced Th17 and Th1 cell responses, resulted in decreased production of the Th17 and Th1-related cytokines IL-1beta, IL-6, IL-23 and IL-12p70 and reduced CD40 expression in DCs. In conclusion, decreased BTLA expression in ocular BD may lead to inappropriate control of the Th17 and Th1 immune responses and DC functions. Therefore, BTLA may be involved in the development and recurrence of this disease. Agonistic agents of BTLA may represent a potential therapeutic approach for the treatment of BD and other inflammatory diseases mediated by abnormal Th17 and Th1 immune responses. PMID:26841832

  19. Lymphocytes from Enlarged Iliac Lymph Nodes as Fusion Partners for the Production of Monoclonal Antibodies after a Single Tail Base Immunization Attempt

    International Nuclear Information System (INIS)

    A novel method of preparing hybridomas producing mouse monoclonal antibodies was established, called “the mouse iliac lymph node method”. Lymphocytes from enlarged iliac lymph nodes from mice injected intramuscularly at the tail base with an emulsion of antigen and Freund’s adjuvant were used for cell fusion. For the most part, lymph node lymphocytes from two mice were used for a single cell fusion attempt. Ovalbumin was used as the antigen and the results of fusion were compared with the results of a previous report (Cell Struct. Funct. 20; 151–156, 1995). Approximately 100 positive wells producing antibody of interest were identified using this method. By comparison, approximately 10 positive wells were identified using the more conventional mouse spleen method after three immunization injections. The relative proportions of hybridomas producing IgM, IgG1, IgG2a, IgG2b, and IgG3, following fusion using iliac lymph node lymphocytes obtained 14 days after injection were 14.0%, 78.7%, 3.2%, 3.5% and 0.5%, respectively. This method demonstrated the following advantages: (1) a single injection of the antigen emulsion was sufficient, (2) the lymph nodes were ready for use 14 days after injection, and (3) a high yield of positive hybridomas was obtained

  20. Irritable bowel syndrome immune hypothesis: the role of lymphocytes and mast cells Hipótesis inmune del síndrome del intestino irritable: Primera parte: papel de los linfocitos y mastocitos

    OpenAIRE

    M. Ortiz Lucas; P. Saz Peiró; J. J. Sebastián Domingo

    2010-01-01

    Objective: To review the available evidence on the role of T-lymphocytes and mast cells in the etiopathogenesis of Irritable Bowel Syndrome. Methods: Bibliographic retrieval on PubMed including the terms "Irritable Bowel Syndrome, "Immune System", "T-Lymphocytes" and "Mast Cells". Results: Twenty-five case-control studies and one randomized controlled trial were retrieved. Noteworthy in the blood is the increase in activated T cells destined to migrate to the bowel in these patients. A high f...

  1. The effect of sex on immune cells in healthy aging: Elderly women have more robust natural killer lymphocytes than do elderly men.

    Science.gov (United States)

    Al-Attar, Ahmad; Presnell, Steven R; Peterson, Charlotte A; Thomas, D Travis; Lutz, Charles T

    2016-06-01

    Immune gender differences have been reported, but are little studied in elderly humans. We compared monocyte and lymphocyte subsets, along with soluble immune mediators in healthy men and women over the age of 70. We also measured natural killer (NK) lymphocyte cytotoxic granule exocytosis, chemokine synthesis, and cytokine synthesis in response to a variety of stimuli. Elderly women had significantly more circulating B cells than men, whereas men had more CD4 central memory T cells and higher monocyte levels. Plasma adiponectin levels were higher in women, plasma retinol-binding protein 4 levels were higher in men, but there were no significant gender differences in C-reactive protein, IL-15, or sphingosine-1-phosphate. Women had a higher ratio of immature CD56(bright) NK cells to mature CD56(dim) NK cells, indicating a gender difference in NK cell maturation in the elderly. Comparing sexes, female mature NK cells had more vigorous cytotoxic granule responses to K562 leukemia cells and IFN-γ responses to NKp46 crosslinking. Moreover, female NK cells were more likely to produce MIP-1β in response to a variety of stimuli. These data show that gender influences NK cell activity in elderly humans. PMID:27059724

  2. Intestinal dysbacteriosis induces changes of T lymphocyte subpopulations in Peyer’s patches of mice and orients the immune response towards humoral immunity

    OpenAIRE

    Gao Fei; Li Ming; Liu Yinhui; Gao Chuanzhou; Wen Shu; Tang Li

    2012-01-01

    Abstract The large numbers of human intestinal microorganisms have a highly co-evolved relationship with the immune system. Dysbacteriosis of intestinal microbiota induces alterations of immune responses, and is closely related to disease development. Peyer’s patches are immune sensors in intestine which exert essential functions during development of inflammatory disease. However, interactions between commensal bacteria and PPs have been poorly characterized. In this study, changes of lympho...

  3. Lymphocyte Functions in Microgravity

    Science.gov (United States)

    Pellis, Neal R.; Risin, Diane; Sundaresan, A.; Cooper, D.; Dawson, David L. (Technical Monitor)

    1999-01-01

    To understand the mechanism of immunity impairment in space it is important to analyze the direct effects of space-related conditions on different lymphocytes functions. Since 1992, we are investigating the effect of modeled and true microgravity (MG) on numerous lymphocyte functions. We had shown that modeled (MMG) and true microgravity inhibit lymphocyte locomotion through type I collagen. Modeled microgravity also suppresses polyclonal and antigen-specific lymphocyte activation. Polyclonal activation of lymphocytes prior to exposure to MMG abrogates the MG-induced inhibition of lymphocyte locomotion. The relationship between activation deficits and the loss of locomotion in MG was investigated using PKC activation by phorbol ester (PMA) and calcium ionophore (ionomycin). Direct activation of PKC by PMA substantially restored the MMG-inhibited lymphocyte locomotion and PHA-induced lymphocyte activation lonomycin by itself did not restore either locomotion or activation of the lymphocytes, indicating that these changes are not related to the impairment in the calcium flux in MMG. Treatment of lymphocytes with PMA before exposure to MMG prevented the loss of locomotion. It was observed that DNA synthesis is not necessary for restoration of locomotion since mitomicin C treated and untreated cells recovered their locomotion to the same level after PKC activation. Our recent data indicate that microgravity may selectively effect the expression of novel Ca2+ independent isoforms of PKC, in particularly PKC sigma and delta. This provides a new insight in understanding of the mechanisms of MG-sensitive cellular functions.

  4. Features of immune metabolism of lymphocytes in pancreatic lymph nodes during experimental steptozotocin-induced diabetes mellitus and after introduction of metformin

    Directory of Open Access Journals (Sweden)

    Putilin D.A.

    2016-06-01

    Full Text Available Background. Metabolic changes in terms of developing diabetes, especially hyperglycemia, can directly affect immune metabolism of lymphocytes. Objective: The aim was to find out the level of mRNA gene expression of Glut1, mTOR and AMPK1α in pancreatic lymphatic nodes (PLN in rats with experimental streptozotocin-induced diabetes mellitus (ESIDM and after introduction of metformin. Methods. Glut1, mTOR and AMPK1α mRNA expression were analyzed by real-time reverse transcriptase-polymerase chain reaction. Total RNA was extracted from PLN tissue by Trizol RNA Prep 100 (Isogen, Russia, according to the manufacturer's instructions. RNA was re-suspended in RNase free water, quantified and subjected to RT-PCR reaction using RT-PCR kit; RT (Syntol, Russia. To determine the level of Glut1, mTOR and AMPK1α mRNA, RT-PCR was performed in real-time by thermal cycler CFX96 ™ Real-Time PCR Detection Systems (Bio-Rad Laboratories, Inc., USA. The relative level of gene expression were studied with rat reference genes GAPDH by the method ΔΔCt. Statistical analysis were conducted using available software «Bio-Rad SFX Manager 3.1» (Bio-Rad, USA. Results. It was established that hyperglycemia caused the transcript induction of genes of glucose transporter Glut1 (in 9,9-28,9 times, p<0,05 and protein kinase mTOR (in 5.3-3.3 times, p<0.05 in cells of PLN. Introduction of metformin to the diabetic rats resulted in an increased level of mRNA gene of AMPK1αby on 87% (p<0.05 on the 3rd week and 38 fold (p<0.05 on the 5th week of ESIDM development and inhibition of mTOR expression in PLN (in 3-14.7 times, p<0.05. Revealed increase of Glut1 and mTOR mRNA genes level in the PLN cells during diabetes can trigger their differentiation in effective pro-inflammatory subpopulation of Th1- and Th17-lymphocytes. Conclusion. Increased level of AMPK1α mRNA and inhibition of mTOR expression in PLN after metformin introduction to diabetic rats gives evidence about the

  5. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercaria- I. analysis of antibody and T-lymphocyte responses in mouse strains developing differing levels of immunity

    Energy Technology Data Exchange (ETDEWEB)

    James, S.L. (Harvard Medical School, Boston, MA); Labine, M.; Sher, A.

    1981-11-15

    The kinetics of cellular and humoral responses directed against schistosomula were examined in mice of three inbred strains which demonstrate differences in the degree of resistance induced by immunization with irradiated cercariae. T-Cell reactivity was observed during the first 4 weeks after vaccination but declined to control levels thereafter. Anti-schistosomulum antibody was first detected 2 weeks after vaccination, peaked by 6 weeks, and persisted as late as 15 weeks. In sera obtained at 6 weeks, antibody activity was detected in affinity chromatography-purified fractions containing IgM, IgA, IgG/sub 1/, IgG/sub 2//sub a/, and IgG/sub 3/ immunoglobulins. In general, the cellular and humoral responses observed in C57Bl/6J mice, which consistently developed a high level of immunity after vaccination, were not significantly different from those observed in C3H/HeJ or CBA/J mice, which achieved only low to moderate levels of immunity. Thus, although antibody production appears to correlate more closely than T lymphocyte responsiveness with the typical long-term resistance pattern observed in this model, the absence of striking differences in parasite-specific antibody levels between mice of these different strains suggests that additional mechanisms may be involved in the development of immunity after vaccination.

  6. Mechanisms of protective immunity against Schistosoma mansoni infection in mice vaccinated with irradiated cercaria- I. analysis of antibody and T-lymphocyte responses in mouse strains developing differing levels of immunity

    International Nuclear Information System (INIS)

    The kinetics of cellular and humoral responses directed against schistosomula were examined in mice of three inbred strains which demonstrate differences in the degree of resistance induced by immunization with irradiated cercariae. T-Cell reactivity was observed during the first 4 weeks after vaccination but declined to control levels thereafter. Anti-schistosomulum antibody was first detected 2 weeks after vaccination, peaked by 6 weeks, and persisted as late as 15 weeks. In sera obtained at 6 weeks, antibody activity was detected in affinity chromatography-purified fractions containing IgM, IgA, IgG1, IgG2/sub a/, and IgG3 immunoglobulins. In general, the cellular and humoral responses observed in C57Bl/6J mice, which consistently developed a high level of immunity after vaccination, were not significantly different from those observed in C3H/HeJ or CBA/J mice, which achieved only low to moderate levels of immunity. Thus, although antibody production appears to correlate more closely than T lymphocyte responsiveness with the typical long-term resistance pattern observed in this model, the absence of striking differences in parasite-specific antibody levels between mice of these different strains suggests that additional mechanisms may be involved in the development of immunity after vaccination

  7. 热性惊厥导致T细胞功能改变的观察%Immune-Functional Changes of T-lymphocytes in Children with Febrile Convulsions

    Institute of Scientific and Technical Information of China (English)

    陈遂 陈遂; 邹峥; 梅魁敏; 陈志军; 徐淑娟

    2000-01-01

    探讨热性惊厥患儿外周血T淋巴细胞免疫功能的变化。方法:应用APSAP法检测82例热性惊厥患儿、40例上呼吸道感染患儿及40例正常小儿T淋巴细胞亚群、CD25抗原在自然状态和PHA激活后的活化状态的百分率。结果:热性惊厥患儿外周血中,CD3、CD4、CD4/CD8比值,均显著低于两对照组;热性惊厥患儿在自然状态下的CD25抗原表达率明显低于两对照组,经PHA刺激后,CD25抗原表达在各组均显著增多,但热性惊厥组仍低于两对照组。结论:热性惊厥患儿存在着细胞免疫损害,这可能是热性惊厥发生和复发的一个重要因素。预防热性惊厥复发,必须从提高细胞免疫功能着手。%To ineestigate the immune-functional changes of T-lymphocytes of peripheral blood in chil dren with febrile convulsions. Methods: Eighty-two children with febrile convulsions, forty with acute upper respiratory tract infection and forty normals were studied. The distribution of T-lymphocytes subsets, the expression of active marker CD25+ before and after PHA stimulation were investigated by APAAP assay. Results:Compared with the other control groups, the percentages of CD3, CD4 and CD4/CD8 ratio of T-lymphocytes were all significantly depressed in the peripheral blood in children with febrile convulsions. The expression rate of CD25 antigen before PHA stimulation was significantly lower than those in two control groups. After PHA stimulation, the expression rates of CD25 antigen were all higher than before, but the rate of the febrile convulsion group was still lower than those of the control groups. Conclusion: Impairment of T-lymphocyte s-mediated immune function was associated with febrile convulsion and it might be a important cause of occurrence of febrile convulsion in children. For prevention and reduction of recurrence and subsequent brain damage, it is important to improve the T-lymphocyte s-mediated immune function of the

  8. Inducible nitric-oxide synthase plays a minimal role in lymphocytic choriomeningitis virus-induced, T cell-mediated protective immunity and immunopathology

    DEFF Research Database (Denmark)

    Bartholdy, C; Nansen, A; Christensen, Jeanette Erbo; Marker, O; Thomsen, Allan Randrup

    . This might suggest a role of NO in regulating vascular reactivity in the context of T cell-mediated inflammation. In conclusion, these findings indicate a minimal role for iNOS/NO in the host response to LCMV. Except for a reduced local oedema in the knockout mice, iNOS/NO seems to be redundant in......By using mice with a targetted disruption in the gene encoding inducible nitric-oxide synthase (iNOS), we have studied the role of nitric oxide (NO) in lymphocytic choriomeningitis virus (LCMV)-induced, T cell-mediated protective immunity and immunopathology. The afferent phase of the T cell...... the up-regulation of proinflammatory cytokine/chemokine genes significantly, nor did it influence the development of fatal meningitis. However, a reduced virus-specific delayed-type hypersensitivity reaction was observed in iNOS-deficient mice compared with both IFN-gamma-deficient and wild-type mice...

  9. Involvement of T- and B-lymphocytes in the immune response to the protein exotoxin and the lipopolysaccharide antigens of Vibrio cholerae

    International Nuclear Information System (INIS)

    The immune response at the level of individual immunocytes to the somatic lipopolysaccharide antigen derived from whole Vibrio cholerae and to the purified protein exotoxin from this organism were studied in terms of the role of T- and B-lymphocytes. By adoptive cell transfer studies with irradiated recipient mice, it was shown that normal spleen cells from normal syngeneic mice could readily transfer the capability of responding to both types of cholera antigens. However, when the spleen cells were depleted of T-cells with anti-theta serum and complement, antibody responsiveness to the LPS antigen, but not the exotoxin, could be achieved in recipients. Furthermore, by appropriate transfer of either bone marrow, thymus, or thymus-marrow cell mixtures to irradiated mice, it was shown that the response to the cholera somatic antigen was relatively independent of thymus cells, whereas the response to exotoxin required ''helper'' T-cells

  10. Lymphocyte Trafficking to Mucosal Tissues

    DEFF Research Database (Denmark)

    Mikhak, Zamaneh; Agace, William Winston; Luster, Andrew D.

    2015-01-01

    Lymphocytes are the key cells of the adaptive immune system that provide antigen-specific responses tailored to the context of antigen exposure. Through cytokine release and antibody production, lymphocytes orchestrate and amplify the recruitment and function of other immune cells and contribute to...... host defense against invading pathogens and the pathogenesis of many inflammatory diseases. Lymphocyte function is critically dependent on their ability to traffic into the correct anatomic locations at the appropriate times. This process is highly regulated and requires that lymphocytes interact with...

  11. Veltuzumab, an anti-CD20 mAb for the treatment of non-Hodgkin's lymphoma, chronic lymphocytic leukemia and immune thrombocytopenic purpura.

    Science.gov (United States)

    Milani, Cannon; Castillo, Jorge

    2009-04-01

    Veltuzumab is a humanized, second-generation anti-CD20 mAb currently under development by Immunomedics Inc for the potential treatment of B-cell non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Licensee Nycomed is developing veltuzumab for the potential treatment of rheumatoid arthritis and immune thrombocytopenic purpura (ITP). Veltuzumab contains 90 to 95% human antibody sequences with identical antigen framework regions to epratuzumab (a humanized anti-CD22 mAb) and similar antigen-binding determinants to rituximab (chimeric, anti-CD20 mAb and the first-line treatment of aggressive and indolent NHL). In vitro studies have demonstrated that veltuzumab has enhanced binding avidities and a stronger effect on complement-dependent cytotoxicity compared with rituximab in selected cell lines. In dose-finding phase I/II clinical trials in patients with low-grade NHL, intravenous veltuzumab demonstrated a substantial rate of complete responses in concurrence with shorter and more tolerable infusions compared with rituximab. Currently there has been no evidence of an immune response to repeated administrations, and no serious adverse events related to veltuzumab treatment in patients with NHL. Veltuzumab is undergoing clinical trials using a low-dose subcutaneous formulation in patients with NHL, CLL and ITP. Prospective, randomized clinical trials are needed to clarify the role veltuzumab will play in a market where the therapy of B-cell lymphoproliferative disorders is dominated by rituximab. PMID:19330725

  12. Cell-mediated immunity to Plasmodium falciparum infection: evidence against the involvement of cytotoxic lymphocytes

    DEFF Research Database (Denmark)

    Theander, T G; Andersen, B J; Pedersen, B K;

    1988-01-01

    Blood mononuclear cells (PBMC) recognizing soluble malaria antigens (SPag) are present in the peripheral blood of individuals clinically immune to malaria, and they proliferate after exposure to such antigens. To test whether these cells have effector activity against Plasmodium falciparum, we...

  13. Construction of exogenous multiple epitopes of helper T lymphocytes and DNA immunization of its chimeric plasmid with HBV pre-S2/S gene

    Institute of Scientific and Technical Information of China (English)

    Wen-Jun Gao; Xiao-Mou Peng; Dong-Ying Xie; Qi-Feng Xie; Zhi-Liang Gao; Ji-Lu Yao

    2004-01-01

    AIM: To design and construct an exogenous multiple epitope of helper T lymphocytes (HTL), and to evaluate its effect on anti-HBs response through DNA immunization.METHODS: Artificial HTL epitope, PADRE and four other HTL epitopes from different proteins were linked together using splicing by overlap extension to generate exogenous multiple epitopes of HTL, MTE5. pcMTE5 and pcHB weregenerated by cloning MTE5 and fragments of HBV pre-S2/S gene into mammalian expression plasmid pcDNA3. Four chimeric plasmids were constructed by cloning MTE5 into the region of pre-S2 gene (Bam HI), 5′ terminal of S gene (HincⅡ, Xba Ⅰ) and 3′ terminal of S gene (Acc Ⅰ) of pcHB respectively. BALB/c mice were used in DNA immunization of the recombinant plasmids. Anti-HBs was detected using Abbott IMx AUSAB test kits.RESULTS: The sequences of MTE5 and the 6 constructs of recombinant plasmids were confirmed to be correct by DNA sequencing. The anti-HBs response of the coinoculation of pcHB and pcMTE5 was much higher than that of the inoculation of pcHB only (136.7±69.1 mIU/mL vs 27.6±17.3 mIU/mL, P<0.01, t = -6.56). Among the 4 chimeric plasmids, only the plasmid in which MTE5 was inserted into the pre-S2 region had good anti-HBs response (57.54±7.68 mIU/mL), and had no significant difference compared with those of pcHB and the co-inoculation of pcHB and pcMTE5.CONCLUSION: Exogenous multiple epitopes of HTL had immune enhancement when they were co-inoculated with pre-S2/S gene or inoculated in the chimeric form at a proper site of pre-S2/S gene of HBV. It might suggest that it was possible to improve hepatitis B vaccine using exogenous multiple epitopes of HTL. The antibody responses were very low using DNA immunization in the study. Thus, the immune enhancement effect of exogenous multiple epitopes of HTL has to be confirmed and the effect on overcoming the drawback of the polymorphism of HLA Ⅱ antigens should also be evaluated after these chimeric plasmids are expressed

  14. Cell-mediated immunity and lymphocyte populations in experimental Argentine hemorrhagic fever (Junín Virus).

    OpenAIRE

    Carballal, G; Oubiña, J. R.; Rondinone, S N; Elsner, B; Frigerio, M J

    1981-01-01

    Guinea pigs infected with the XJ prototype strain of Junín virus reproduce the main features of Argentine hemorrhagic fever, showing hemorrhages, leukothrombocytopenia, and focal lymphoid tissue necrosis. Viral lymphotropism is shown by the presence of viral antigens, severe cytopathic effect, and high virus titers in lymphoid organs. A pronounced depression of humoral immune response to sheep erythrocytes as well as to the virus is described. This study was carried out to determine whether c...

  15. NLRC5 elicits antitumor immunity by enhancing processing and presentation of tumor antigens to CD8(+) T lymphocytes.

    Science.gov (United States)

    Rodriguez, Galaxia M; Bobbala, Diwakar; Serrano, Daniel; Mayhue, Marian; Champagne, Audrey; Saucier, Caroline; Steimle, Viktor; Kufer, Thomas A; Menendez, Alfredo; Ramanathan, Sheela; Ilangumaran, Subburaj

    2016-06-01

    Cancers can escape immunesurveillance by diminishing the expression of MHC class-I molecules (MHC-I) and components of the antigen-processing machinery (APM). Developing new approaches to reverse these defects could boost the efforts to restore antitumor immunity. Recent studies have shown that the expression of MHC-I and antigen-processing molecules is transcriptionally regulated by NOD-like receptor CARD domain containing 5 (NLRC5). To investigate whether NLRC5 could be used to improve tumor immunogenicity, we established stable lines of B16-F10 melanoma cells expressing NLRC5 (B16-5), the T cell co-stimulatory molecule CD80 (B16-CD80) or both (B16-5/80). Cells harboring NLRC5 constitutively expressed MHC-I and LMP2, LMP7 and TAP1 genes of the APM. The B16-5 cells efficiently presented the melanoma antigenic peptide gp10025-33 to Pmel-1 TCR transgenic CD8(+) T cells and induced their proliferation. In the presence of CD80, B16-5 cells stimulated Pmel-1 cells even without the addition of gp100 peptide, indicating that NLRC5 facilitated the processing and presentation of endogenous tumor antigen. Upon subcutaneous implantation, B16-5 cells showed markedly reduced tumor growth in C57BL/6 hosts but not in immunodeficient hosts, indicating that the NLRC5-expressing tumor cells elicited antitumor immunity. Following intravenous injection, B16-5 and B16-5/80 cells formed fewer lung tumor foci compared to control cells. In mice depleted of CD8(+) T cells, B16-5 cells formed large subcutaneous and lung tumors. Finally, immunization with irradiated B16-5 cells conferred protection against challenge by parental B16 cells. Collectively, our findings indicate that NLRC5 could be exploited to restore tumor immunogenicity and to stimulate protective antitumor immunity. PMID:27471621

  16. From Innate to Adaptive Immune Response in Muscular Dystrophies and Skeletal Muscle Regeneration: The Role of Lymphocytes

    Directory of Open Access Journals (Sweden)

    Luca Madaro

    2014-01-01

    Full Text Available Skeletal muscle is able to restore contractile functionality after injury thanks to its ability to regenerate. Following muscle necrosis, debris is removed by macrophages, and muscle satellite cells (MuSCs, the muscle stem cells, are activated and subsequently proliferate, migrate, and form muscle fibers restoring muscle functionality. In most muscle dystrophies (MDs, MuSCs fail to properly proliferate, differentiate, or replenish the stem cell compartment, leading to fibrotic deposition. However, besides MuSCs, interstitial nonmyogenic cells and inflammatory cells also play a key role in orchestrating muscle repair. A complete understanding of the complexity of these mechanisms should allow the design of interventions to attenuate MDs pathology without disrupting regenerative processes. In this review we will focus on the contribution of immune cells in the onset and progression of MDs, with particular emphasis on Duchenne muscular dystrophy (DMD. We will briefly summarize the current knowledge and recent advances made in our understanding of the involvement of different innate immune cells in MDs and will move on to critically evaluate the possible role of cell populations within the acquired immune response. Revisiting previous observations in the light of recent evidence will likely change our current view of the onset and progression of the disease.

  17. From Innate to Adaptive Immune Response in Muscular Dystrophies and Skeletal Muscle Regeneration: The Role of Lymphocytes

    Science.gov (United States)

    Madaro, Luca; Bouché, Marina

    2014-01-01

    Skeletal muscle is able to restore contractile functionality after injury thanks to its ability to regenerate. Following muscle necrosis, debris is removed by macrophages, and muscle satellite cells (MuSCs), the muscle stem cells, are activated and subsequently proliferate, migrate, and form muscle fibers restoring muscle functionality. In most muscle dystrophies (MDs), MuSCs fail to properly proliferate, differentiate, or replenish the stem cell compartment, leading to fibrotic deposition. However, besides MuSCs, interstitial nonmyogenic cells and inflammatory cells also play a key role in orchestrating muscle repair. A complete understanding of the complexity of these mechanisms should allow the design of interventions to attenuate MDs pathology without disrupting regenerative processes. In this review we will focus on the contribution of immune cells in the onset and progression of MDs, with particular emphasis on Duchenne muscular dystrophy (DMD). We will briefly summarize the current knowledge and recent advances made in our understanding of the involvement of different innate immune cells in MDs and will move on to critically evaluate the possible role of cell populations within the acquired immune response. Revisiting previous observations in the light of recent evidence will likely change our current view of the onset and progression of the disease. PMID:25028653

  18. Consumption of purple sweet potato leaves modulates human immune response: T-lymphocyte functions, lytic activity of natural killer cell and antibody production

    Institute of Scientific and Technical Information of China (English)

    Chiao-Ming Chen; Sing-Chung Li; Ya-Ling Lin; Ching-Yun Hsu; Ming-Jer Shieh; Jen-Fang Liu

    2005-01-01

    AIM: To study the immunological effects of physiological doses of purple sweet potato leaves (PSPL).METHODS: The randomized crossover study (two periods,each lasting for 2 wk) involved 16 healthy non-smoking adults of normal weight. The 6-wk study consisted of a run-in (wk 1) PSPL diet (daily consumption of 200 g PSPL) or a control diet (low polyphenols, with the amount of carotenoids adjusted to the same level as that of PSPL) (wk 2-3), washout diet (wk 4), and switched diet (wk 5-6). Fasting blood was collected weekly in the morning. T-lymphocyte function was assessed via the proliferation and secretion of immunoreactive cytokines.Salivary IgA secretion and the specific cytotoxic activities of cytotoxic T lymphocytes and natural killer (NK) cells were determined.RESULTS: The plasma β-carotene level increased with time in both groups, while the plasma polyphenol level decreased in the control group, and no significant difference was detected between the two groups.Although plasma polyphenol levels did not significantly increase in the PSPL group at the end of the study, they were significantly elevated in urine. PSPL consumption produced a significant increase in proliferation responsiveness of peripheral blood mononuclear cells (PBMC) and their secretion of immunoreactive IL-2 and IL-4. As well, lytic activity in NK cells was elevated in a time-dependent fashion. Salivary TgA secretion significantly decreased in control group after 2 wk, and returned to baseline following dietary switch to PSPL.CONCLUSION: Consumption of PSPL modulates various immune functions including increased proliferation responsiveness of PBMC, secretion of cytokines IL-2 and IL-4, and the lytic activity of NK cells. The responsible determinants of PSPL remain to be elucidated, as does the biological significance of the present observations.

  19. HLA-G is a component of the chronic lymphocytic leukemia escape repertoire to generate immune suppression: impact of the HLA-G 14 base pair (rs66554220) polymorphism

    Science.gov (United States)

    Rizzo, Roberta; Audrito, Valentina; Vacca, Paola; Rossi, Davide; Brusa, Davide; Stignani, Marina; Bortolotti, Daria; D’Arena, Giovanni; Coscia, Marta; Laurenti, Luca; Forconi, Francesco; Gaidano, Gianluca; Mingari, Maria Cristina; Moretta, Lorenzo; Malavasi, Fabio; Deaglio, Silvia

    2014-01-01

    This work investigates the possibility that HLA-G, a molecule modulating innate and adaptive immunity, is part of an immune escape strategy of chronic lymphocytic leukemia cells. A 14 base pair insertion/deletion polymorphism (rs66554220) in the 3′-untranslated region of HLA-G influences mRNA stability and protein expression. The analysis of a cohort of patients with chronic lymphocytic leukemia confirmed that del/del individuals are characterized by higher levels of surface and soluble HLA-G than subjects with the other two genotypes. In line with its role in immunomodulation, the percentage of regulatory T lymphocytes is higher in del/del patients than in patients with the other genotypes and correlates with the amounts of surface or soluble HLA-G. Furthermore, addition of sHLA-G-rich plasma from patients with chronic lymphocytic leukemia induces natural killer cell apoptosis and impairs natural killer cell lysis, with effects proportional to the amount of soluble HLA-G added. Lastly, the presence of an HLA-G 14 base pair polymorphism is of prognostic value, with del/del patients showing reduced overall survival, as compared to those with other genotypes. These results suggest that: (i) the HLA-G 14 base pair polymorphism influences the levels of surface and soluble HLA-G expression, and (ii) the over-expression of HLA-G molecules contributes to creating tolerogenic conditions. PMID:24362551

  20. Lentiviral vector delivery of human interleukin-7 (hIL-7 to human immune system (HIS mice expands T lymphocyte populations.

    Directory of Open Access Journals (Sweden)

    Ryan M O'Connell

    Full Text Available Genetically modified mice carrying engrafted human tissues provide useful models to study human cell biology in physiologically relevant contexts. However, there remain several obstacles limiting the compatibility of human cells within their mouse hosts. Among these is inadequate cross-reactvitiy between certain mouse cytokines and human cellular receptors, depriving the graft of important survival and growth signals. To circumvent this problem, we utilized a lentivirus-based delivery system to express physiologically relevant levels of human interleukin-7 (hIL-7 in Rag2-/-gammac-/- mice following a single intravenous injection. hIL-7 promoted homeostatic proliferation of both adoptively transferred and endogenously generated T-cells in Rag2-/-gammac-/- Human Immune System (HIS mice. Interestingly, we found that hIL-7 increased T lymphocyte numbers in the spleens of HIV infected HIS mice without affecting viral load. Taken together, our study unveils a versatile approach to deliver human cytokines to HIS mice, to both improve engraftment and determine the impact of cytokines on human diseases.

  1. Immune response to recombinant adenovirus in humans: capsid components from viral input are targets for vector-specific cytotoxic T lymphocytes.

    Science.gov (United States)

    Molinier-Frenkel, V; Gahery-Segard, H; Mehtali, M; Le Boulaire, C; Ribault, S; Boulanger, P; Tursz, T; Guillet, J G; Farace, F

    2000-08-01

    We previously demonstrated that a single injection of 10(9) PFU of recombinant adenovirus into patients induces strong vector-specific immune responses (H. Gahéry-Ségard, V. Molinier-Frenkel, C. Le Boulaire, P. Saulnier, P. Opolon, R. Lengagne, E. Gautier, A. Le Cesne, L. Zitvogel, A. Venet, C. Schatz, M. Courtney, T. Le Chevalier, T. Tursz, J.-G. Guillet, and F. Farace, J. Clin. Investig. 100:2218-2226, 1997). In the present study we analyzed the mechanism of vector recognition by cytotoxic T lymphocytes (CTL). CD8(+) CTL lines were derived from two patients and maintained in long-term cultures. Target cell infections with E1-deleted and E1-plus E2-deleted adenoviruses, as well as transcription-blocking experiments with actinomycin D, revealed that host T-cell recognition did not require viral gene transcription. Target cells treated with brefeldin A were not lysed, indicating that viral input protein-derived peptides are associated with HLA class I molecules. Using recombinant capsid component-loaded targets, we observed that the three major proteins could be recognized. These results raise the question of the use of multideleted adenoviruses for gene therapy in the quest to diminish antivector CTL responses. PMID:10906225

  2. Immune Response to Recombinant Adenovirus in Humans: Capsid Components from Viral Input Are Targets for Vector-Specific Cytotoxic T Lymphocytes

    Science.gov (United States)

    Molinier-Frenkel, Valérie; Gahery-Segard, Hanne; Mehtali, Majid; Le Boulaire, Christophe; Ribault, Sébastien; Boulanger, Pierre; Tursz, Thomas; Guillet, Jean-Gérard; Farace, Françoise

    2000-01-01

    We previously demonstrated that a single injection of 109 PFU of recombinant adenovirus into patients induces strong vector-specific immune responses (H. Gahéry-Ségard, V. Molinier-Frenkel, C. Le Boulaire, P. Saulnier, P. Opolon, R. Lengagne, E. Gautier, A. Le Cesne, L. Zitvogel, A. Venet, C. Schatz, M. Courtney, T. Le Chevalier, T. Tursz, J.-G. Guillet, and F. Farace, J. Clin. Investig. 100:2218–2226, 1997). In the present study we analyzed the mechanism of vector recognition by cytotoxic T lymphocytes (CTL). CD8+ CTL lines were derived from two patients and maintained in long-term cultures. Target cell infections with E1-deleted and E1-plus E2-deleted adenoviruses, as well as transcription-blocking experiments with actinomycin D, revealed that host T-cell recognition did not require viral gene transcription. Target cells treated with brefeldin A were not lysed, indicating that viral input protein-derived peptides are associated with HLA class I molecules. Using recombinant capsid component-loaded targets, we observed that the three major proteins could be recognized. These results raise the question of the use of multideleted adenoviruses for gene therapy in the quest to diminish antivector CTL responses. PMID:10906225

  3. Radiosensitivities of sensitized lymphocytes

    International Nuclear Information System (INIS)

    Immunization of mice with cell antigens such as allogeneic tumor cells or xenogeneic erythrocytes raises a variety of immune reactions mediated by T lymphocytes: i.e. delayed type hypersensitivity (DTH), cytotoxicity, and antibody production. The radiosensitivities of these reactions were examined in mice exposed to 600 R x-irradiation a few hours before or after immunization. 1) DTH to xenogeneic erythrocytes, as demonstrated by footpad reaction, was not suppressed by irradiation 3 h before or after immunization. DTH to allogeneic tumor cells, as demonstrated by a migration inhibition test, hardly developed in mice that had been irradiated before or after immunization. It may have belonged to distinct types of delayed reactions which were mediated by distinct subpopulations of T lymphocytes. 2) Cytotoxicity against allogeneic cells and xenogeneic erythrocytes showed almost the same radiosensitivity. It was scarcely detected in mice that had been irradiated before immunization. However, a low but definite degree of cytotoxicity was detected in mice that had been irradiated only a few hours after immunization. Solubilized allogeneic cells instead of native cells were used as immunizing antigens. It was also possible for precursor cells with cytotoxicity to acquire a radioresistant nature by immunization of solubilized antigens, but native cells were required as stimulation for radioresistant precursor cells to differentiated into nature cytotoxic effector cells. 3) Antibody production against xenogeneic erythrocytes or allogeneic cells was almost completely depleted in mice that had been irradiated before or after immunization. It is possible that antibody production essentially requires cell division and clonal expansion of B lymphocytes. (Bell, E.)

  4. Opinion: Interactions of innate and adaptive lymphocytes

    OpenAIRE

    Gasteiger, Georg; Rudensky, Alexander Y.

    2014-01-01

    Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a mo...

  5. Do lampreys have lymphocytes? The Spi evidence

    OpenAIRE

    Shintani, Seikou; Terzic, Janos; Sato, Akie; Saraga-Babic, Mirna; O'hUigin, Colm; Tichy, Herbert; Klein, Jan

    2000-01-01

    It is generally accepted that living jawless vertebrates (lampreys and hagfishes) lack the capability of mounting an adaptive immune response. At the same time, however, there are reports describing histological evidence for the presence in agnathan tissues of lymphocytes, the key players in adaptive immunity. The question therefore arises whether the cells identified morphologically as lymphocytes are true lymphocytes in terms of their genetic developmental program. In this study, evidence i...

  6. Blood B Lymphocyte Stimulator (BLyS)/BAFF levels may reflect natural immunity to HIV in highly exposed uninfected Beninese Commercial Sex Workers

    Science.gov (United States)

    Sabourin-Poirier, Catherine; Fourcade, Lyvia; Chagnon-Choquet, Josiane; Labbé, Annie-Claude; Alary, Michel; Guédou, Fernand; Poudrier, Johanne; Roger, Michel

    2016-01-01

    We have previously shown that excess B lymphocyte Stimulator (BLyS)/BAFF in plasma and on surface of blood dendritic cells (DC) of HIV-infected progressors coincides with B-cell dysregulations and increased frequencies of “precursor” innate marginal zone (MZ)-like B-cells. In contrast, both blood BLyS levels and frequencies of this population remained unaltered in HIV elite-controllers. Based on these observations, we hypothesized that control of BLyS and innate B-cell status could be associated with natural immunity against HIV infection. Therefore, we assessed blood BLyS levels and B-cell status in HIV highly-exposed commercial sex workers (CSWs) from Benin. We found blood BLyS levels of HIV-uninfected CSWs were lower than those observed in both HIV-infected CSW and HIV-uninfected non-CSW groups. Furthermore, levels of BLyS expression on blood T-cells and monocytes were lower in HIV-uninfected CSWs when compared to HIV-infected CSWs, but higher than those observed for HIV-uninfected non-CSWs. Concomitantly, HIV-infected CSWs presented a dysregulated blood B-cell compartment, characterized by increased total IgG1, increased frequencies of populations presenting immature and/or innate profiles and a higher ratio of IgG+/IgA+ plasmablasts. In contrast, relatively low levels of BLyS in the blood of HIV-uninfected CSWs coincided with a rather preserved B-cell compartment. PMID:27561453

  7. Induction of immune tolerance in asthmatic mice by vaccination with DNA encoding an allergen-cytotoxic T lymphocyte-associated antigen 4 combination.

    Science.gov (United States)

    Zhang, Fang; Huang, Gang; Hu, Bo; Song, Yong; Shi, Yi

    2011-05-01

    Allergen-specific immunotherapy is a potential treatment for allergic diseases. We constructed an allergen-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-encoding DNA vaccine, administered it directly to antigen-presenting cells (APCs), and investigated its ability and mechanisms to ameliorate allergic airway inflammation in an asthmatic mouse model. An allergen-CTLA-4 DNA plasmid (OVA-CTLA-4-pcDNA₃.₁) encoding an ovalbumin (OVA) and the mouse CTLA-4 extracellular domain was constructed and transfected into COS-7 cells to obtain the fusion protein OVA-CTLA-4, which was able to bind the B7 ligand on dendritic cells (DCs), and induced CD25⁺ Foxp3⁺ regulatory T (Treg) cells by the coculture of naive CD4⁺ T cells with DCs in vitro. In an animal study, BALB/c mice were sensitized and challenged with OVA to establish the asthmatic model. Vaccination with a high dose of OVA-CTLA-4-pcDNA₃.₁ significantly decreased interleukin-4 (IL-4) and IL-5 levels and eosinophil counts and prevented OVA-induced reduction of the gamma interferon level in the bronchoalveolar lavage fluid. In addition, these mice suffered less severe airway inflammation and had lower levels of OVA-specific IgE and IgG1 titers in serum. Also, high-dose OVA-CTLA-4-pcDNA₃.₁ vaccination inhibited the development of airway hyperreactivity and prevented OVA-induced reduction of the percentages of Foxp3⁺ Treg cells in the spleen. Our results indicate that a high dose of allergen-CTLA-4-encoding DNA vaccine was more effective in preventing an allergen-induced Th2-skewed immune response through the induction of Treg cells and may be a new alternative therapy for asthma. PMID:21346053

  8. Blood B Lymphocyte Stimulator (BLyS)/BAFF levels may reflect natural immunity to HIV in highly exposed uninfected Beninese Commercial Sex Workers.

    Science.gov (United States)

    Sabourin-Poirier, Catherine; Fourcade, Lyvia; Chagnon-Choquet, Josiane; Labbé, Annie-Claude; Alary, Michel; Guédou, Fernand; Poudrier, Johanne; Roger, Michel

    2016-01-01

    We have previously shown that excess B lymphocyte Stimulator (BLyS)/BAFF in plasma and on surface of blood dendritic cells (DC) of HIV-infected progressors coincides with B-cell dysregulations and increased frequencies of "precursor" innate marginal zone (MZ)-like B-cells. In contrast, both blood BLyS levels and frequencies of this population remained unaltered in HIV elite-controllers. Based on these observations, we hypothesized that control of BLyS and innate B-cell status could be associated with natural immunity against HIV infection. Therefore, we assessed blood BLyS levels and B-cell status in HIV highly-exposed commercial sex workers (CSWs) from Benin. We found blood BLyS levels of HIV-uninfected CSWs were lower than those observed in both HIV-infected CSW and HIV-uninfected non-CSW groups. Furthermore, levels of BLyS expression on blood T-cells and monocytes were lower in HIV-uninfected CSWs when compared to HIV-infected CSWs, but higher than those observed for HIV-uninfected non-CSWs. Concomitantly, HIV-infected CSWs presented a dysregulated blood B-cell compartment, characterized by increased total IgG1, increased frequencies of populations presenting immature and/or innate profiles and a higher ratio of IgG(+)/IgA(+) plasmablasts. In contrast, relatively low levels of BLyS in the blood of HIV-uninfected CSWs coincided with a rather preserved B-cell compartment. PMID:27561453

  9. Shen-Qi-Jie-Yu-Fang has antidepressant effects in a rodent model of postpartum depression by regulating the immune organs and subsets of T lymphocytes

    Directory of Open Access Journals (Sweden)

    Qu M

    2015-06-01

    Full Text Available Miao Qu,1 Qisheng Tang,1 Xiaoli Li,1 Ruizhen Zhao,1 Jingya Li,1 Hong Xu,2 Yushan Gao,2 Yingqiu Mao31Third Affiliated Hospital, 2School of Basic Medical Sciences, 3Center of Scientific Research, Beijing University of Chinese Medicine, Beijing, People’s Republic of China Background: Shen-Qi-Jie-Yu-Fang (SJ Fang is a herbal preparation used in traditional Chinese medicine, and is a potentially important new therapeutic agent in postpartum depression (PPD. Previously, we have elucidated the effects of SJ Fang on hormone receptors and monoamine neurotransmitters involved in the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes in PPD rats. However, the immune-modulating effects of SJ Fang in PPD are still unknown. In this study, we explored the effects of SJ Fang on the immune organs and subsets of T lymphocytes in PPD rats.Methods: PPD was created in Sprague-Dawley rats by inducing hormone-simulated pregnancy followed by hormone withdrawal. After hormone withdrawal, the PPD rats were then treated with fluoxetine at 1, 2, and 4 weeks, and the SJ Fang rats were also treated at 1, 2, and 4 weeks. Depressive behavior in the rats was evaluated by the forced swim test, sucrose consumption test, and open field test. The thymus index and spleen index were calculated. Hematoxylin-eosin staining was used to identify pathological features in the thymus and spleen. CD3, CD4, and CD8 lymphocyte subsets were analyzed by flow cytometry.Results: Both fluoxetine and SJ Fang increased immobility time, sucrose consumption, an horizontal and vertical movements. After 4 weeks of treatment with fluoxetine or SJ Fang, the thymus index and spleen index were significantly higher than at baseline, and the morphology of the thymus and spleen were returning to normal. Two weeks after hormone withdrawal, subsets of T lymphocytes indicated a shift from immune activation to immune suppression, which was reversed by 4 weeks of treatment with fluoxetine or SJ

  10. Effects of PQL on levels of immunal proteins, C3, C4 and expressions of CD4, CD8, and CD25 on lymphocytes of peripherial blood in patients with breast carcinoma undergoing radiotherapy

    International Nuclear Information System (INIS)

    Objective: To evaluate the effects of panaxatriol in quinquefolium leaf (PQL) on immune functions in the patients with breast carcinoma undergoing radiotherapy. Methods: Thirty patients with breast carcinoma undergoing radiotherapy were randomly divided into 2 groups: panaxatriol treatment group (n=17) and control group (n=13). All patients in panaxatriol treatment group were administrated with PQL as well as radiotherapy, no administration in control group. After radiotherapy with 40 Gy, the white cells count and IgG, IgA, IgM, C3, and C4 values, and the percentages of CD4+, CD8+, CD25+ and lymphocyte transformation rate of peripheral blood in the patients were examined. Results: There were (4.02 ± 0.67) x 109 ·L-1 and (6.17 ± 1.20) x 109 ·L-1 white blood cells, respectively, in control and PQL groups. The lymphocyte transformation rate of peripheral blood were 7966 ± 1562 in the control group, while 18035 ± 1577 in PQL group, which was significantly higher than that in control group (P+ and CD25+ T lymphocytes in PQL group were significantly higher than those in control group (P<0.05, P<0.001). Conclusion: The PQL could enhance the cellular immune function in patients with breast carcinoma undergoing radiotherapy. (authors)

  11. Immunity

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008254 Prokaryotic expression and immunogenicity of Fba,a novel fibronectin-binding protein of group A streptococcus.MA Cuiqing(马翠柳),et al.Dept Immunol,Basic Med Coll,Hebei Med Univ,Shijiazhuang 050017.Chin J Infect Dis 2008;26(3):146-150.Objective To express the novel fibronectin-binding protein Fba ofgroupAstreptococcus(GAS)and analyze its immunogenicity,so to evaluate the immune responses to GAS infection.Methods fbagene was amplified by

  12. Ontogeny of Innate T Lymphocytes – Some Innate Lymphocytes are More Innate than Others

    OpenAIRE

    Vermijlen, David; Prinz, Immo

    2014-01-01

    Innate lymphocytes have recently received a lot of attention. However, there are different ideas about the definition of what is “innate” in lymphocytes. Lymphocytes without V(D)J-rearranged antigen receptors are now termed innate lymphoid cells (ILCs) and include cells formerly known as natural killer (NK) cells. Also, lymphocytes that are innate should be able to recognize microbial or stress-induced patterns and react rapidly without prior sensitization, as opposed to adaptive immune respo...

  13. Ontogeny of innate T lymphocytes - some innate lymphocytes are more innate then others

    OpenAIRE

    David eVermijlen; Immo ePrinz

    2014-01-01

    Innate lymphocytes have recently received a lot of attention. However, there are different ideas about the definition of what is innate in lymphocytes. Lymphocytes without V(D)J-rearranged antigen receptors are now termed innate lymphoid cells (ILCs) and include cells formerly known as NK cells. Also, lymphocytes that are innate should be able to recognize microbial or stress-induced patterns and react rapidly without prior sensitization, as opposed to adaptive immune responses. Formally, gen...

  14. Recombinant human interleukin-2 reverses in vitro-deficient cell-mediated immune responses to tuberculin purified protein derivative by lymphocytes of tuberculous patients.

    OpenAIRE

    Shiratsuchi, H; Okuda, Y.; Tsuyuguchi, I

    1987-01-01

    In vitro lymphocyte proliferative response to purified protein derivative of tuberculin (PPD) was investigated in patients with tuberculosis. Peripheral blood lymphocytes (PBL) from patients with advanced, refractory tuberculosis showed a significantly depressed response compared with the response of PBL from patients with newly diagnosed tuberculosis (P less than 0.01). A further characterization of this low responsiveness to PPD revealed that PBL from these advanced tuberculous patients fai...

  15. Diversity in the Immune System

    OpenAIRE

    Borghans, J.A.M.; Boer, R.J. de

    2000-01-01

    Diversity is one of the key characteristics of the vertebrate immune system. Lymphocyte repertoires of at least 3x10⁷ different clonotypes protect humans against infections, while avoiding unwanted immune responses against self-peptides and innocuous antigens. It is this lymphocyte diversity that forms the main difference between the immune systems of invertebrate and vertebrate species.

  16. Long term effects on the immune system following local radiation therapy for breast cancer. I. Cellular composition of the peripheral blood lymphocyte population

    International Nuclear Information System (INIS)

    Local radiation therapy for breast cancer depletes the blood of various subsets of lymphocytes. Previous studies showed that the recovery is still incomplete at 30 months. To further elucidate the recovery the authors examined blood lymphocyte counts of 138 disease-free women and various lymphocyte subsets in 102 of these patients. Total lymphocyte counts of the irradiated patients were still significantly reduced 10-11 years after treatment. This reduction was mainly attributable to a subnormal level of T-cells as determined by the monoclonal antibody Leu-1 and the ability to form rosettes with sheep erythrocytes, whereas the number of non-T cells, expressing C'3 receptors, did not differ significantly from the controls. Within the T-cell population a subset with helper/inducer phenotypes, detected by Leu-3a antibodies, was significantly reduced even 10-11 years after irradiation. The duration of the radiation induced reductions of different lymphocyte subsets may be related to the physiological turn-over of the cells or a changed distribution of cells in the body

  17. Effects of metal ions on cyprinid fish immune response: In vitro effects of Zn2+ and Mn2+ on the mitogenic response of carp pronephros lymphocytes

    International Nuclear Information System (INIS)

    Lymphocytes from the pronephros of carp (Cyprinus carpio L) have been subjected to transformation by mitogens, concanavalin A (Con A), phytohemagglutinin (PHA), and lipopolysaccharides (LPS), with Zn or Mn at varying concentrations. Addition of Zn2+ (10(-7) to 10(-3) M) to mitogen-stimulated T and B cells enhanced [3H]thymidine incorporation. Addition of 10(-5) M Zn2+ inhibited the response to Con A, PHA, and LPS. At this concentration, Zn was toxic. Addition of Mn2+ (10(-7) to 10(-3) M) to mitogen-stimulated lymphocytes enhanced [3H]thymidine incorporation. This effect was observed with Con A- and PHA-stimulated lymphocytes, but not with LPS-stimulated lymphocytes. In contrast, addition of 10(-1) M Mn2+ to lymphocyte cultures exerted an inhibitor on the response to Con A or to PHA, while the response to LPS was unaffected. Addition of 10(-1) M Mn2+ to Con A- or PHA-stimulated cultures at different times after initiation of stimulation indicated that Mn2+ was inhibitory only when it was added before the first 16 hr of cultures. The inhibition induced by 10(-1) M Mn2+ could be reversed by adding 2 mM CaCl2 to the culture

  18. Clinical significance of HLA-DR+, CD19+, CD10+ immature B-cell phenotype and CD34+ cell detection in bone marrow lymphocytes from children affected with immune thrombocytopenic purpura.

    Science.gov (United States)

    Callea, V; Comis, M; Iaria, G; Sculli, G; Morabito, F; Lombardo, V T

    1997-01-01

    In children with immune thrombocytopenic purpura (ITP), bone marrow lymphocytes can express the common acute lymphoblastic leukemia antigen (CALLA) pattern with no evidence of leukemia or lymphoma. Bone marrow lymphocytes from 23 children and 20 adults affected with ITP were studied to determine the incidence and the clinical impact of lymphocytes with the immature B-cell phenotype and CD34+ cell expression. In this investigation we identified a group consisting of 52% of the children who showed the immature B phenotype, while the remaining 48%, similarly to adult ITP displayed an increase of T-cell antigens. CD34 was positive in 53% of children, but it was present in only half of the patients with the immature B phenotype and it was always absent in adults. IgH genes disclosed a germline configuration in all six patients in the immature B phenotype group. No difference was found in the two groups of children in terms of age, presentation of the disease or final outcome. Finally, no patient in either children's group has developed an acute lymphoproliferative disorder. PMID:9299867

  19. Irritable bowel syndrome immune hypothesis: the role of lymphocytes and mast cells Hipótesis inmune del síndrome del intestino irritable: Primera parte: papel de los linfocitos y mastocitos

    Directory of Open Access Journals (Sweden)

    M. Ortiz Lucas

    2010-11-01

    Full Text Available Objective: To review the available evidence on the role of T-lymphocytes and mast cells in the etiopathogenesis of Irritable Bowel Syndrome. Methods: Bibliographic retrieval on PubMed including the terms "Irritable Bowel Syndrome, "Immune System", "T-Lymphocytes" and "Mast Cells". Results: Twenty-five case-control studies and one randomized controlled trial were retrieved. Noteworthy in the blood is the increase in activated T cells destined to migrate to the bowel in these patients. A high frequency of T-lymphocytes is described in the intestinal mucosa, although the study findings are, at times, contradictory. An evident increase in mast cells (and in their activity between the terminal ileum and descending colon is also observed. Conclusions: The heterogeneity of diagnostic criteria and experimentation methods could account for some of the differences in the results found in the selected research. There are indications that give reason to believe these patients have "low-grade intestinal inflammation", and the increase in T-lymphocytes and mast cells has been associated with disorders found in IBS such as the communication between the intestine and the nervous system, the increase in intestinal permeability and changes in the microbiota.Objetivo: Revisar la evidencia disponible sobre el papel de los linfocitos T y mastocitos en la etiopatogenia del Síndrome del Intestino Irritable. de las vías biliares. Métodos: Recuperación bibliográfica en PubMed incluyendo los términos "Irritable Bowel Syndrome, "Immune System", "T-Lymphocytes" y "Mast Cells". Resultados: Se recuperaron 25 estudios casos-control y un ensayo clínico aleatorizado. A nivel sanguíneo destaca el aumento de células T activadas destinadas a migrar al intestino en estos pacientes. En la mucosa intestinal se describe un patrón elevado de linfocitos T, aunque los resultados de los estudios son en ocasiones contradictorios, y un aumento claro de mastocitos (y de su

  20. Treatment with anti-FasL antibody preserves memory lymphocytes and virus-specific cellular immunity in macaques challenged with simian immunodeficiency virus

    OpenAIRE

    Poonia, Bhawna; Salvato, Maria S.; Yagita, Hideo; Maeda, Toshihiro; Okumura, Ko; Pauza, C. David

    2009-01-01

    Immune deficiency viruses such as SIV in macaques or HIV-1 in human beings have evolved mechanisms to defeat host immunity that also impact the efficacy of vaccines. A key factor for vaccine protection is whether immune responses elicited by prior immunization remain at levels sufficient to limit disease progression once a host is exposed to the pathogen. One potential mechanism for escaping pre-existing immunity is to trigger death among antigen-activated cells. We tested whether FasL/CD178 ...

  1. Alpha-fetoprotein triggers hepatoma cells escaping from immune surveillance through altering the expression of Fas/FasL and tumor necrosis factor related apoptosis-inducing ligand and its receptor of lymphocytes and liver cancer cells

    Institute of Scientific and Technical Information of China (English)

    Meng-Sen Li; Qiu-Ling Ma; Qian Chen; Xin-Hua Liu; Ping-Feng Li; Guo-Guang Du; Gang Li

    2005-01-01

    AIM: To investigate the mechanism of α-fetoprotein (AFP)in escaping from the host immune surveillance of hepatocellular carcinoma.METHODS: AFP purified from human umbilical blood was administrated into the cultured human lymphoma Jurkat T cell line or hepatoma cell line, Bel7402 in vitro. The expression of tumor necrosis factor related apoptosisinducing ligand (TRAIL) and its receptor (TRAILR) mRNA were analyzed by Northern blot and Western blot wasused to detect the expression of Fas and Fas ligand (FasL)protein.RESULTS: AFP (20 mg/L) could promote the expression of FasL and TRAIL, and inhibit the expression of Fas and TRAILR of Bel7402 cells. For Jurkat cell line, AFP could suppress the expression of FasL and TRAIL, and stimulate the expression of Fas and TRAILR. AFP also could synergize with Bel7402 cells to inhibit the expression of FasL protein and TRAIL mRNA in Jurkat cells. The monoclonal antibody against AFP (anti-AFP) could abolish these functions of AFP.CONCLUSION: AFP is able to promote the expression of FasL and TRAIL in hepatoma cells and enhance the expression of Fas and TRAILR in lymphocytes. These could elicit the escape of hepatocellular carcinoma cells from the host's lymphocytes immune surveillance.

  2. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  3. Proliferation induced by Plasmodium falciparum antigen and interleukin-2 production by lymphocytes isolated from malaria-immune individuals

    DEFF Research Database (Denmark)

    Theander, T G; Bygbjerg, I C; Jepsen, S; Svenson, M; Kharazmi, A; Larsen, P B; Bendtzen, K

    1986-01-01

    -immune individuals, the proliferative response and the interleukin-2 (IL-2) production of SPAg-activated mononuclear cells (MNCs) from individuals unexposed, sensitized, and immune to malaria were measured. It was found that MNC isolated from malaria-immune individuals proliferated in response to SPAg and that this...... activation resulted in measurable IL-2 production in 5 of 10 MNC cultures. MNC isolates from most unexposed individuals did not respond to SPAg. To establish which cells responded to SPAg, different subpopulations of MNCs were tested. Only T helper cells were found to respond, and they responded only when...... cocultured with monocytes. The finding of parasite-specific T helper cells in the blood of malaria-immune individuals and the fact that some of these cells were able to produce IL-2 in vitro support the hypothesis that in malaria the cellular part of the protective immune response is initiated by immune T...

  4. In vitro generation of cytotoxic lymphocytes against radiation-and radiation leukemia virus-induced tumors. III. Suppression of anti-tumor immunity in vitro by lymphocytes of mice undergoing radiation leukemia virus-induced leukemogenesis

    International Nuclear Information System (INIS)

    Adult C57BL/6 mice exposed to fractionated irradiation or inoculated with the radiation leukemia virus (RadLV), develop high incidence (80 to 100%) of lymphatic leukemias within 3 to 6 months. RadLV-induced lymphomas can elicit cytotoxic responses in vitro in lymphocytes of preimmunized syngeneic mice. As soon as 5 d after RadLV inoculation, and during the entire leukemogenic process, suppressor T cells are detectable in the spleen that are capable of specifically abrogating generation of syngeneic anti-tumor cytotoxic cells in vitro. Mice exposed to fractionated x irradiation do not develop suppressor cells. These findings suggest that although RadLV has been isolated from radiation-induced leukemias, x-ray- and RadLV-induced leukemogenesis do not seem to involve a common viral etilogy, and that induction of suppressor cells during RadLV leukemogenesis may be essential for tumor progression

  5. Histopathology and immune histochemistry of red tattoo reactions. Interface dermatitis is the lead pathology, with increase in T-lymphocytes and Langerhans cells suggesting an allergic pathomechanism

    DEFF Research Database (Denmark)

    Høgsberg, T; Thomsen, B M; Serup, J

    2015-01-01

    BACKGROUND: The majority of tattoo reactions are affiliated to red pigmented areas and often suspected to be allergic in nature. A sizeable series of biopsies of such reactions has not previously been performed. The aim of this study was to type and grade epidermal and dermal changes in tattoo...... reactions to red/red nuances by microscopy and immunochemistry relevant for the assessment of a possible allergic pathomechanism. METHODS: Skin biopsies were taken from red tattoo reactions, graded by conventional microscopy and stained for T and B-lymphocytes, Langerhans cells, macrophages and tumour......-α was common. CONCLUSION: The predominant histological pattern of chronic tattoo reactions in red/red nuances is interface dermatitis. T-lymphocytes and Langerhans cells are increased suggesting an allergic pathomechanism. TNF-α may contribute to reactions. In many cases, overlapping reactive patterns...

  6. Induction of Immune Tolerance in Asthmatic Mice by Vaccination with DNA Encoding an Allergen–Cytotoxic T Lymphocyte-Associated Antigen 4 Combination ▿

    OpenAIRE

    Zhang, Fang; Huang, Gang; Hu, Bo; Song, Yong; Shi, Yi

    2011-01-01

    Allergen-specific immunotherapy is a potential treatment for allergic diseases. We constructed an allergen–cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-encoding DNA vaccine, administered it directly to antigen-presenting cells (APCs), and investigated its ability and mechanisms to ameliorate allergic airway inflammation in an asthmatic mouse model. An allergen-CTLA-4 DNA plasmid (OVA-CTLA-4-pcDNA3.1) encoding an ovalbumin (OVA) and the mouse CTLA-4 extracellular domain was constructed...

  7. Autoimmune hepatitis in association with lymphocytic colitis.

    LENUS (Irish Health Repository)

    Cronin, Edmond M

    2012-02-03

    Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.

  8. Natural CD8{sup +}25{sup +} regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Yufeng; Zhang, Xueshu; Zhao, Tuo; Li, Wei; Xiang, Jim, E-mail: jim.xiang@saskcancer.ca

    2013-08-16

    Highlights: •CD8{sup +}25{sup +} regulatory T cells secrete tolerogenic exosomes. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes exhibit immunosuppressive effect. •CD8{sup +}25{sup +} regulatory T cell-derived exosomes inhibit antitumor immunity. -- Abstract: Natural CD4{sup +}25{sup +} and CD8{sup +}25{sup +} regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8{sup +}25{sup +} Tr cells from C57BL/6 mouse naive CD8{sup +} T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXO{sub Tr}) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXO{sub Tr} had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DC{sub OVA}) plus Tr cells or EXO{sub Tr}, and then assessed OVA-specific CD8{sup +} T cell responses using PE-H-2K{sup b}/OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10{sub OVA} melanoma cells. We demonstrated that DC{sub OVA}-stimulated CD8{sup +} T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p < 0.05), and from 8/8 to 2/8 and 5/8 mice DC{sub OVA} (p < 0.05) in immunized mice with co-injection of Tr cells and EXO{sub Tr}, respectively. Our results indicate that natural CD8{sup +}25{sup +} Tr cell-released EXOs, alike CD8{sup +}25{sup +} Tr cells, can inhibit CD8{sup +} T cell responses and antitumor immunity. Therefore, EXOs derived from

  9. Protective effects of melatonin against irradiation: an in vitro study to assess immune damages in blood and bone marrow lymphocytes of animal cells

    International Nuclear Information System (INIS)

    Human health can be adversely affected by exposure to radiation. This can come in the form of simple sunlight, to X-ray exposure. Recently there is a great increase in the number of personnel working with ionizing radiations, together with the development of nuclear weapon. Tissue damage, whether resulting in a sunburn or in thyroid cancer etc. is caused by 'ionizing' radiation. Further, Local acute reaction to radiation exposure during 'radiation therapy' is more frequent than whole body radiation which interferes with the cellular activity (mostly proliferative cells such as skin, blood, cancer, digestive tract cells) and leads to the suppression of immune system function. 1) It penetrates the cells and tissue and can produce severe damage to the required/pathogenic cells. 2) Indirect actions are (free radical generation, destruction of receptor sites etc.) still not known. 3) Severe immune dysfunction after several doses of radiation is a common factor. What does the term mean? It describes the release of free radicals from the molecules struck by the radiation. Raising glutathione levels protects cells from damage by the most dangerous of free radicals (the hydroxyl-radical) released when ionizing radiation hits us. Therefore, in search of a protective measurement to reduce the hazardous effects of radiation on immune system we propose an approach to reduce the damages caused by ion radiation to immune cells by using melatonin which has been established as a strong antioxidant and immune-modulator. (author)

  10. γδ T LYMPHOCYTES AS A FIRST LINE OF IMMUNE DEFENSE: OLD AND NEW WAYS OF ANTIGEN RECOGNITION AND IMPLICATIONS FOR CANCER IMMUNOTHERAPY.

    Directory of Open Access Journals (Sweden)

    Maria Raffaella eZocchi

    2014-11-01

    Full Text Available Among γδT cells, the Vδ1 subset, resident in epithelial tissues, is implied in the defense against viruses, fungi and certain hematological malignancies, while the circulating Vδ2 subpopulation mainly respond to mycobacteria and solid tumors. Both subsets can be activated by stress-induced molecules (MIC-A, MIC-B, ULBPs to produce pro-inflammatory cytokines and lytic enzymes and destroy bacteria or damaged cells. γδT lymphocytes can also recognize lipids, as those associated to M. tuberculosis, presented by the CD1 molecule, or phosphoantigens (P-Ag, either autologous, which accumulates in virus-infected cells, or microbial produced by prokaryotes and parasites. In cancer cells P-Ag accumulate due to alterations in the mevalonate pathway; recently, butyrophilin 3A1 has been shown to be the presenting molecule for P-Ag. Of interest, aminobisphosphonates indirectly activate Vδ2 T cells inducing the accumulation of P-Ag. Based on these data, γδT lymphocytes are attractive effectors for cancer immunotherapy. However, the results obtained in clinical trials so far have been disappointing: this review will focus on the possible reasons of this failure as well as on suggestions for implementation of the therapeutic strategies.

  11. Aging of the Immune System: How Much Can the Adaptive Immune System Adapt?

    OpenAIRE

    Weng, Nan-ping

    2006-01-01

    The competency of the adaptive immune function decreases with age, primarily because of the decline in production of naïve lymphocytes in the bone marrow and thymus as well as the expansion of incompetent memory lymphocytes. Here I discuss the recent progress on age-associated changes in lymphocytes and their effect on the adaptive immune system.

  12. Natural CD8+25+ regulatory T cell-secreted exosomes capable of suppressing cytotoxic T lymphocyte-mediated immunity against B16 melanoma

    International Nuclear Information System (INIS)

    Highlights: •CD8+25+ regulatory T cells secrete tolerogenic exosomes. •CD8+25+ regulatory T cell-derived exosomes exhibit immunosuppressive effect. •CD8+25+ regulatory T cell-derived exosomes inhibit antitumor immunity. -- Abstract: Natural CD4+25+ and CD8+25+ regulatory T (Tr) cells have been shown to inhibit autoimmune diseases. Immune cells secrete exosomes (EXOs), which are crucial for immune regulation. However, immunomodulatory effect of natural Tr cell-secreted EXOs is unknown. In this study, we purified natural CD8+25+ Tr cells from C57BL/6 mouse naive CD8+ T cells, and in vitro amplified them with CD3/CD28 beads. EXOs (EXOTr) were purified from Tr cell’s culture supernatants by differential ultracentrifugation and analyzed by electron microscopy, Western blot and flow cytometry. Our data showed that EXOTr had a “saucer” or round shape with 50–100 nm in diameter, contained EXO-associated markers LAMP-1 and CD9, and expressed natural Tr cell markers CD25 and GITR. To assess immunomodulatory effect, we i.v. immunized C57BL/6 mice with ovalbumin (OVA)-pulsed DCs (DCOVA) plus Tr cells or EXOTr, and then assessed OVA-specific CD8+ T cell responses using PE-H-2Kb/OVA tetramer and FITC-anti-CD8 antibody staining by flow cytometry and antitumor immunity in immunized mice with challenge of OVA-expressing BL6–10OVA melanoma cells. We demonstrated that DCOVA-stimulated CD8+ T cell responses and protective antitumor immunity significantly dropped from 2.52% to 1.08% and 1.81% (p OVA (p Tr, respectively. Our results indicate that natural CD8+25+ Tr cell-released EXOs, alike CD8+25+ Tr cells, can inhibit CD8+ T cell responses and antitumor immunity. Therefore, EXOs derived from natural CD4+25+ and CD8+25+ Tr cells may become an alternative for immunotherapy of autoimmune diseases

  13. Immune responses to epstein-barr virus in atomic bomb survivors: Study of precursor frequency of cytotoxic lymphocytes and titer levels of anti-Epstein-Barr virus-related antibodies

    International Nuclear Information System (INIS)

    Precursor frequencies of cytotoxic lymphocytes to autologous Epstein-Barr virus-transformed B cells and serum titers of anti-Epstein-Barr virus-related antibodies were measured in 68 atomic bomb survivors to clarify the immune mechanism controlling Epstein-Barr virus infection. The precursor frequency was negatively correlated with the titer of anti-early antigen lgG, which is probably produced at the stage of viral reactivation. A positive correlation between the precursor frequency and titer of anti-Epstein-Barr virus-associated nuclear antigen antibody was also observed, indicating that the precursor frequency reflects the degree of in vivo destruction by T cells of the virus-infected cells. These results suggest that T-cell memory specific to Epstein-Barr virus keeps the virus under control and that the precursor frequency assay is useful for the evaluation of immune responses to Epstein-Barr virus. However, no significant effect of atomic bomb radiation on the precursor frequency was observed in the present study, probably due to the limited number of participants. 24 refs., 4 figs., 2 tabs

  14. Induction of human papilloma virus E6/E7-specific cytotoxic T-lymphocyte activity in immune-tolerant, E6/E7-transgenic mic

    NARCIS (Netherlands)

    Riezebos-Brilman, A; Regts, J; Freyschmidt, EJ; Dontje, B; Wilschut, J; Daemen, T

    2005-01-01

    Despite promising preclinical results of various therapeutic anticancer immunization strategies, these approaches may not be effective enough to eradicate tumors in cancer patients. While most animal models are based on fast-growing transplantable tumors, malignancies in, for example, cervical cance

  15. Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus by qRT-PCR

    Directory of Open Access Journals (Sweden)

    Iona E. Maher

    2014-03-01

    Full Text Available Investigation of the immune response of the koala (Phascolarctos cinereus is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV, which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala’s susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1 and Th2 lymphocyte responses are important to an individual’s susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala’s adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4, interleukin 6 (IL-6, interleukin 10 (IL-10 and interferon gamma (IFNγ along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A. Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not

  16. Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus) by qRT-PCR.

    Science.gov (United States)

    Maher, Iona E; Griffith, Joanna E; Lau, Quintin; Reeves, Thomas; Higgins, Damien P

    2014-01-01

    Investigation of the immune response of the koala (Phascolarctos cinereus) is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV), which is of 100% prevalence in northern Australia, has been proposed as an important agent of immune suppression that could explain the koala's susceptibility to disease. The correct balance of T regulatory, T helper 1 (Th1) and Th2 lymphocyte responses are important to an individual's susceptibility or resistance to chlamydial infection. The ability to study chlamydial or KoRV pathogenesis, effects of environmental stressors on immunity, and the response of koalas to vaccines under development, by examining the koala's adaptive response to natural infection or in-vitro stimulation, has been limited to date by a paucity of species- specific reagents. In this study we have used cytokine sequences from four marsupial genomes to identify mRNA sequences for key T regulatory, Th1 and Th2 cytokines interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 10 (IL-10) and interferon gamma (IFNγ) along with CD4 and CD8β. The koala sequences used for primer design showed >58% homology with grey short-tailed opossum, >71% with tammar wallaby and 78% with Tasmanian devil amino acid sequences. We report the development of real-time RT-PCR assays to measure the expression of these genes in unstimulated cells and after three common mitogen stimulation protocols (phorbol myristate acetate/ionomycin, phorbol myristate acetate/phytohemagglutinin and concanavalin A). Phorbol myristate acetate/ionomycin was found to be the most effective mitogen to up-regulate the production of IL-4, IL-10 and IFNγ. IL-6 production was not consistently up-regulated by

  17. Lymphocyte apoptosis in murine Pneumocystis pneumonia

    Directory of Open Access Journals (Sweden)

    Ruan Sanbao

    2009-06-01

    Full Text Available Abstract Background Apoptosis of lymphocytes is important in the termination of an immune response to infection but has also been shown to have detrimental effects in animal models of systemic infection and sepsis. We sought to characterize lymphocyte apoptosis in an animal model of pneumonia due to Pneumocystis murina, an infection localized to the lungs. Methods Control mice and mice depleted of CD4+ lymphocytes were inoculated with Pneumocystis. Apoptosis of lung and spleen lymphocytes was assayed by flow cytometry and PCR assay of apoptotic proteins. Results In control mice, apoptosis of lung lymphocytes was maximal just after the infection was cleared from lung tissue and then declined. However, in CD4-depleted mice, apoptosis was also upregulated in recruited lymphocytes in spite of progressive infection. In splenic lymphocytes, apoptosis was observed early at 1 week after inoculation and then declined. Apoptosis of lung lymphocytes in control mice was associated with a decrease in mRNA for Bcl-2 and an increase in mRNA for Bim. In CD4-depleted mice, lavaged CD8+ cells did change intracellular Bcl-2 but showed increased mRNA for Bim. Conclusion Apoptosis of both pulmonary and extrapulmonary lymphocytes is part of the normal host response to Pneumocystis but is also triggered in CD4-deficient animals with progressive infection. In normal mice apoptosis of pulmonary lymphocytes may serve to terminate the immune response in lung tissue. Apoptosis of lung lymphocytes takes place via both the intrinsic and extrinsic apoptotic pathways and is associated with changes in both pro- and anti-apoptotic proteins.

  18. Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients

    Directory of Open Access Journals (Sweden)

    Caimi Luigi

    2010-11-01

    Full Text Available Abstract Background The immune defects occurring in chronic lymphocytic leukemia are responsible for the frequent occurrence of infections and autoimmune phenomena, and may be involved in the initiation and maintenance of the malignant clone. Here, we evaluated the quantitative defects of newly produced B and T lymphocytes. Methods The output of B and T lymphocytes from the production and maturation sites was analyzed in chronic lymphocytic leukemia patients and healthy controls by quantifying kappa-deleting recombination excision circles (KRECs and T-cell receptor excision circles (TRECs by a Real-Time PCR assay that simultaneously detects both targets. T-lymphocyte subsets were analyzed by six-color flow cytometric analysis. Data comparison was performed by two-sided Mann-Whitney test. Results KRECs level was reduced in untreated chronic lymphocytic leukemia patients studied at the very early stage of the disease, whereas the release of TRECs+ cells was preserved. Furthermore, the observed increase of CD4+ lymphocytes could be ascribed to the accumulation of CD4+ cells with effector memory phenotype. Conclusions The decreased number of newly produced B lymphocytes in these patients is likely related to a homeostatic mechanism by which the immune system balances the abnormal B-cell expansion. This feature may precede the profound defect of humoral immunity characterizing the later stages of the disease.

  19. Recurrent abortions and lymphocyte transfusions.

    Science.gov (United States)

    Bjercke, S

    1994-05-01

    Normal pregnancies depend on successful implantation of the placenta in the uterus. The trophoblast which forms the ultimate interface between the fetal and maternal tissue seems to lack the foreign (allo) antigens (namely HLA/TLX) required to induce immunological rejection reactions in the mother. It was previously believed that the trophoblast expressed paternal allo antigens and that successful pregnancies were dependent on so called 'kind' (non-cytotoxic or non-complement binding) blocking antibodies in order to protect the fetal unit from maternal cytotoxic T-cells and -antibodies. Blocking antibodies attached to paternal antigens on the trophoblast were assumed to prevent maternal cytotoxic T cell and cytotoxic antibodies from recognising the trophoblast as foreign tissue. On this assumption it was reasoned that transfusions of paternal HLA-expressing lymphocytes would increase maternal antipaternal HLA (TLX) blocking antibodies and thus be beneficial to women who experienced multiple miscarriages. There is, however, no scientific evidence for a specific immune response after lymphocyte transfusions that fulfil this function. Immunological tests, as for example mixed lymphocyte culture (MLC), on peripheral blood lymphocytes do not seem to reflect the local immune state in the uterus, either in the pregnant or the non-pregnant state. Since the trophoblast forms the ultimate interface between fetal and maternal tissue, its structure, secretions, and interaction with the decidua must be of definite importance for implantation of the blastocyst and growth of the embryo. PMID:8009967

  20. Major histocompatibility complex-linked immune-responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice

    International Nuclear Information System (INIS)

    Female murine T cells can respond to the Y antigen of male cells by generating cytotoxic T-killer lymphocytes. Responsiveness is linked to several H-2 genes. Two types of low responders can be distinguished: the B10.A(5R)(H-2/sup i5/) strain, a low responder because it lacks Y-specific precursor T cells able to differentiate into cytotoxic T-killer cells; and the CBA/J (H-2/sup k/) strain, a low responder because it lacks Y-specific T-helper cells able to support differentiation of T-killer cell precursors. B10.A(5R) stem cells differentiating in an x-irradiated (CBA/J x C57BL/6) (H-2/sup k/ x H-2/sup b/)F1 host respond to Y antigen by generating T-killer cells whereas CBA/J stem cells do not. The results are consistent with the hypothesis that diversity of T-cell receptors is generated by somatic mutation of germ-line genes encoding specificity for self-H-2. A detailed account of this hypothesis is presented

  1. Role of STAT3 in regulatory T lymphocyte plasticity during acute graft-vs.-host-disease

    OpenAIRE

    Fujino, Masayuki; Li, Xiao-Kang

    2013-01-01

    Regulatory T (Treg) lymphocytes are important mediators of the allogeneic immune response, although the mechanisms by which they are controlled are not fully understood. Studies conducted in mice, including a recent article in Immunity by Laurence et al., have shown that STAT3 is an important factor involved in the instability of natural Treg (nTreg) lymphocytes and the generation of induced Treg (iTreg) lymphocytes. The authors used T lymphocytes obtained from Foxp3-GFP reporter mice, which ...

  2. Immune Response to Recombinant Adenovirus in Humans: Capsid Components from Viral Input Are Targets for Vector-Specific Cytotoxic T Lymphocytes

    OpenAIRE

    Molinier-Frenkel, Valérie; Gahery-Segard, Hanne; Mehtali, Majid; Le Boulaire, Christophe; Ribault, Sébastien; Boulanger, Pierre; Tursz, Thomas; Guillet, Jean-Gérard; Farace, Françoise

    2000-01-01

    We previously demonstrated that a single injection of 109 PFU of recombinant adenovirus into patients induces strong vector-specific immune responses (H. Gahéry-Ségard, V. Molinier-Frenkel, C. Le Boulaire, P. Saulnier, P. Opolon, R. Lengagne, E. Gautier, A. Le Cesne, L. Zitvogel, A. Venet, C. Schatz, M. Courtney, T. Le Chevalier, T. Tursz, J.-G. Guillet, and F. Farace, J. Clin. Investig. 100:2218–2226, 1997). In the present study we analyzed the mechanism of vector recognition by cytotoxic T ...

  3. Complex expression patterns of lymphocyte-specific genes during the development of cartilaginous fish implicate unique lymphoid tissues in generating an immune repertoire

    Science.gov (United States)

    Miracle, A. L.; Anderson, M. K.; Litman, R. T.; Walsh, C. J.; Luer, C. A.; Rothenberg, E. V.; Litman, G. W.

    2001-01-01

    Cartilaginous fish express canonical B and T cell recognition genes, but their lymphoid organs and lymphocyte development have been poorly defined. Here, the expression of Ig, TCR, recombination-activating gene (Rag)-1 and terminal deoxynucleosidase (TdT) genes has been used to identify roles of various lymphoid tissues throughout development in the cartilaginous fish, Raja eglanteria (clearnose skate). In embryogenesis, Ig and TCR genes are sharply up-regulated at 8 weeks of development. At this stage TCR and TdT expression is limited to the thymus; later, TCR gene expression appears in peripheral sites in hatchlings and adults, suggesting that the thymus is a source of T cells as in mammals. B cell gene expression indicates more complex roles for the spleen and two special organs of cartilaginous fish-the Leydig and epigonal (gonad-associated) organs. In the adult, the Leydig organ is the site of the highest IgM and IgX expression. However, the spleen is the first site of IgM expression, while IgX is expressed first in gonad, liver, Leydig and even thymus. Distinctive spatiotemporal patterns of Ig light chain gene expression also are seen. A subset of Ig genes is pre-rearranged in the germline of the cartilaginous fish, making expression possible without rearrangement. To assess whether this allows differential developmental regulation, IgM and IgX heavy chain cDNA sequences from specific tissues and developmental stages have been compared with known germline-joined genomic sequences. Both non-productively rearranged genes and germline-joined genes are transcribed in the embryo and hatchling, but not in the adult.

  4. Alterations of T cell receptor Vβ repertoire of CD8 T lymphocytes in immune tolerance induction in two hemophilia A patients with inhibitors

    Directory of Open Access Journals (Sweden)

    Sakurai Yoshihiko

    2011-01-01

    Full Text Available Background/Aim. Hemophilia A patients with inhibitors are treated effectively with immune tolerance induction (ITI therapy. Although anti-idiotypic antibodies may play a certain role in the underlying mechanism, the detailed mechanism by which ITI produces a curative effect remains unknown. The aim of this study was to clarify the immunological aspect of ITI. Methods. Longitudinal T-cell receptor (TCR analysis was performed during ITI. TCR variable region α-chain and β-chain repertoires were serially analyzed for peripheral blood mononuclear cells (PBMCs, CD4 T cells, and CD8 T cells from 2 hemophilia inhibitor patients treated with ITI (Patients 1 and 2. Furthermore, to see whether skewing observed in TCR analysis resulted from clonality alterations, T-cell clonality was investigated using complementarity-determining region 3 (CDR3 size spectratyping. Results. In the patient 1, inhibitor titer remained to be 19.6 BU/mL for 596 days after ITI commencement, and ITI was unsuccessful. In the patient 2, inhibitor titer disappeared 434 days after ITI commencement, and ITI was successful. In both cases, skewing of TCR variable region α/β-chain repertoires was observed in CD8 T cell subset, whereas not in CD4 T cell subset. Conclusion. Alteration of TCR repertoires, especially TCR variable region β-chain repertoire of CD8 T cells, was distinct between successful and unsuccessful cases, suggesting that immunological response in the early phase affected the ITI outcomes.

  5. Ontogeny of innate T lymphocytes - some innate lymphocytes are more innate then others

    Directory of Open Access Journals (Sweden)

    David eVermijlen

    2014-10-01

    Full Text Available Innate lymphocytes have recently received a lot of attention. However, there are different ideas about the definition of what is innate in lymphocytes. Lymphocytes without V(DJ-rearranged antigen receptors are now termed innate lymphoid cells (ILCs and include cells formerly known as NK cells. Also, lymphocytes that are innate should be able to recognize microbial or stress-induced patterns and react rapidly without prior sensitization, as opposed to adaptive immune responses. Formally, genuine innate lymphocytes would be present before or at birth. Here we review the ontogeny of human and mouse innate T lymphocyte populations. We focus on γδ T cells, which are prototype lymphocytes that often use their V(DJ rearrangement machinery to generate genetically encoded predetermined recombinations of antigen receptors. We make parallels between the development of γδ T cells with that of innate aβ T cells (invariant (iNKT and mucosa-associated invariant T (MAIT cells and compare this with the ontogeny of innate B cells and innate lymphoid cells (ILCs, including NK cells. We conclude that some subsets are more innate than others, i.e. innate lymphocytes that are made primarily early in utero during gestation while others are made after birth. In practice, a ranking of innateness by ontogeny has implications for the reconstitution of innate lymphocyte subsets after hematopoietic stem cell transplantation (HSCT.

  6. Evaluación de la inmunidad celular en caninos: prueba de proliferación de linfocitos in vitro Evaluation of cellular immunity in dogs: in vitro lymphocyte proliferation test

    Directory of Open Access Journals (Sweden)

    L. G Ramayo

    2005-12-01

    Full Text Available La prueba de proliferación de linfocitos inducida por mitógenos in vitro se utiliza para evaluar la inmunidad celular. En el presente trabajo, se comparan los resultados obtenidos con el método tradicional, que utiliza linfocitos purificados para el cultivo y la captación de timidina tritiada como método de medición de la proliferación (LP- ³H, con otras dos metodologías: el uso de sangre entera con revelado por captación de timidina tritiada (SE-³H y el uso de linfocitos purificados con revelado por ensayo colorimétrico con MTT (LP-MTT. Se trabajó sobre muestras de 12 caninos clínicamente sanos que fueron procesadas por las tres metodologías. Se utilizó Concanavalina A como mitógeno y el Indice de Estimulación (IE como expresión de los resultados. El método de SE-³H arrojó valores de IE significativamente mayores que la técnica clásica, por lo que resultaría útil para evaluar la proliferación linfocitaria en caninos en nuestras condiciones de trabajo. El método de LP-MTT mostró valores de IE significativamente menores, por lo que se requieren más estudios para evaluar su posible uso en la medición de la funcionalidad linfocitaria. Sobre la base de los resultados obtenidos se estableció un rango normal de valores de IE para cada método.In vitro mitogen induced lymphocyte proliferation test is widely used for evaluation of cellmediated immunity. In the present work, we compare the results of the traditional method, which uses gradient isolated lymphocytes as the source of cells for the culture and tritiated thymidine incorporation to measure proliferative response (LP- ³H, with other two methods: culture of whole blood and proliferation measure with ³H- thymidine (SE-³H, and culture of isolated lymphocytes and proliferation evaluation with a colorimetric assay using MTT (LP-MTT. Blood samples of twelve adult, healthy dogs were processed by the three mentioned methods, using Concanavalin- A as mitogen and the

  7. The influence of the long term voyage on the lymphocytes of nuclear-powered submarine crews

    International Nuclear Information System (INIS)

    Objective: To study the influence of long term voyage on the number and activity of the nuclear-powered submarine crew's lymphocytes. Methods: Before and after long term voyage, the total number lymphocytes of peripheral blood were measured; pured lymphocytes were planted to count the number of T lymphocyte colonies; and the apoptosis rate T lymphocyte was measured. Results: After long term voyage, the total amount of lymphocyte is increased; the T lymphocyte make much more colonies after planting; and the apoptosis rate of T lymphocyte is raised. Conclusion: Long term voyage in nuclear-powered submarine can affect the account of peripheral blood lymphocyte and the activity of T lymphocyte. The cumulative effect of micro-radiation in cabin can affect the immune function of the crew, more protection need to be strengthened to enhance the health. (authors)

  8. Phenotypic and Functional Analysis of Porcine T Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    李华; 陈应华

    2001-01-01

    Porcine and other higher mammals express clusters of differentiation (CD) antigens on the surface of T lymphocytes, such as CD2, CD3, CD4, CD8, etc. However, in porcine, a high percentage of the CD4+ CD8-T lymphocyte subpopulation exist in the peripheral blood and the ratio of the CD4+ and CD8+ T lymphocyte subpopulations is reversed. These differences bring new challenges to better understanding of the phenotype and function of porcine T lymphocytes in antigen recognition and immune response.

  9. Studies on lymphocyte function in gynecological cancer patients, 2

    International Nuclear Information System (INIS)

    In the second of these three serial studies the effects of therapeutic Co60 irradiation on the lymphocytes were examined with special reference to their reactivity against mitogens and antilymphocyte antibody to yield the following results : 1) Total lymphocyte counts in the peripheral blood and the absolute T cell number decreased after irradiation, although no changes were found in T cell percentage. 2) In order to evaluate immune response in uterine cancer patients undergoing therapeutic irradiation, in vitro lymphocyte transformation tests using PHA, Con A, PWM and PPD, as well as mensuration of IgG, IGA, IgM, C3, and C4, were carried out on the blood obtained from each patient before and during therapy : During irradiation, the lymphocyte transformation values against PHA and Con A were depressed, but no significant changes were found in the values of IgG, IgA, and IgM. In some patients, however, the IgG, IgM, C3 and C4 values were slightly increased after irradiation. 3) Using sera with high anti-lymphocyte antibody titers obtained from SLE patients, a cyto toxicity test against normal lymphocytes and lymphocytes from Co60 -treated patients was carried out : In approptiate seral dilution, less cytotoxicity was found in lymphocytes obtained from Co60 treated patients than in those obtained from normal patients lymphocytes, i.e. lymphocytes from Co60 treated patents were found to be more resistant to the cytotoxic sera than normal lymphocytes. (author)

  10. A subset of memory CD4+ helper T lymphocytes identified by expression of Pgp-1

    OpenAIRE

    1989-01-01

    The Pgp-1 glycoprotein (Ly-24 antigen) is acquired by mature murine T lymphocytes at the time of primary antigen stimulation Pgp-1 was previously shown to be a useful cell surface marker for distinguishing antigen-specific memory CD8+ T lymphocytes after immunization. Here we demonstrate that this observation extends to CD4+ T lymphocytes. Antigen-specific CD4+ T cells in mice immunized with sperm whale myoglobin or keyhole limpet hemocyanin were contained nearly exclusively in the minor Pgp-...

  11. Canine lymphocyte activating factor (LAF)

    International Nuclear Information System (INIS)

    The immune response of an animal is the sum of the result of the interaction of various cells mainly through soluble mediators. It is not enough to look at specific cell populations, it is also necessary to study the interactions between purified cell population. The effect of one subpopulation on another is via soluble mediators. We have been studying one (of several) such mediators in its relation to radiation effects on the immune response. Lymphocyte activating factor (LAF) is defined functionally as a potentiator of the response of thymocytes to phytohemagglutinin (PHA) or concanavalin (con-A). It can also elicit response of unstimulated subpopulations separated from the thymus. It is a product of adherent populations, presumably macrophages. It has been shown to be produced by human, rabbit, and mouse cells, but has not been reported in the dog. It also was shown to be present in higher concentrations in irradiated mice than in comparable unirradiated mice. We have shown that LAF is produced by plastic-adherent populations derived from peripheral blood. Currently we are working to determine the lymphocyte subpopulations with which LAF interacts

  12. The behavior of pig lymphocyte populations in vivo

    International Nuclear Information System (INIS)

    Lymphocyte migration provides the means of rapidly recognizing and responding to antigen and widely disseminating the resulting immune response. The porcine lymphoid system differs from that of man in structural inversion of lymph nodes and route of lymphocyte recirculation and the existence of two Peyer's patch types, one of which differs from the conventional pattern in structure, cell content and lack of lymphocyte traffic and in its regression in old age. Recirculating T and B lymphocytes enter and leave spleen and lymph nodes by the blood but Null cells do not; lymphocytes also migrate through nonlymphoid tissues. The lung is one such important site, with a small migration in and out of alveolar space and a large traffic associated with the blood vessel wall, predominantly involving T cells. Blood lymphocytes hardly traffic into the peritoneal cavity, yet major traffic of particulate material or cells is possible in this important site of abdominal defense, so often used for immunization, and follows a distinct, well defined route. Cells migrate out of subcutaneous tissue via the draining node. Lymphocytes are produced and emigrate into blood from labelled thymus. They differ in size and surface phenotype from both thymocytes and peripheral T cells. Lymphocytes also migrate from blood into most tissues. In most nonlymphoid tissues, entry relates to blood flow but in many lymphoid tissues it is an active process which differs in tempo and extent, eg, between different nodes and between the two Peyer's patch types

  13. The invasive chytrid fungus of amphibians paralyzes lymphocyte responses

    OpenAIRE

    Fites, J. Scott; Ramsey, Jeremy P.; Holden, Whitney M.; Collier, Sarah P.; Sutherland, Danica M.; Reinert, Laura K.; Gayek, A. Sophia; Dermody, Terence S.; Aune, Thomas M.; Oswald-Richter, Kyra; Rollins-Smith, Louise A.

    2013-01-01

    The chytrid fungus, Batrachochytrium dendrobatidis, causes chytridiomycosis and is a major contributor to global amphibian declines. Although amphibians have robust immune defenses, clearance of this pathogen is impaired. Because inhibition of host immunity is a common survival strategy of pathogenic fungi, we hypothesized that B. dendrobatidis evades clearance by inhibiting immune functions. We found that B. dendrobatidis cells and supernantants impaired lymphocyte proliferation and induced ...

  14. MAJOR AND LYMPHOCYTE POPULATIONS OF HUMAN PERIPHERAL BLOOD LYMPHOCYTES AND THEIR REFERENCE VALUES, AS ASSAYED BY MULTI-COLOUR CYTOMETRY

    Directory of Open Access Journals (Sweden)

    S. V. Khaidukov

    2014-07-01

    Full Text Available Abstract. Determination of lymphocyte subpopulations and their phenotypes is an important diagnostic feature, in order to elucidate some disturbances connected with immune system functioning. However, insufficient data are obtained when analyzing only major populations of peripheral lymphocytes. In order to perform clinical diagnostics, the data about minor lymphocytic populations and activated cellular pools seem to be more pertinent.Studies of peripheral blood cell subpopulations of healthy donors performed in different Russian regions allowed to assess quantitative distribution intervals for both major and minor immune cell subpopulations in humans. The results obtained, as compared with data from literature, provide an evidence for similar reference intervals for main immune cell subpopulations in healthy donors, independent on their habitation area.Present work has resulted into development of algorithms for cytometric studies and generation of certain panels of monoclonal antibodies enabling evaluation of all main lymphocyte subpopulations, as well as their minor subsets participating in emerging immune response. The distribution intervals have been estimated for such minor subpopulations, as B1- and B2-lymphocytes, memory B-cells, γδ- and αβT-cells, regulatory and naїve T-cells, cytotoxic and secretory NK-cell polupations.The results of present study, while been performed with peripheral blood of healthy donors, may provide a basis of reference values when studying subpopulation profile of immune cells.

  15. Community Immunity (Herd Immunity)

    Science.gov (United States)

    ... Read more information on enabling JavaScript. Skip Content Marketing Share this: Main Content Area ​Community Immunity ("Herd" ... population is immunized, protecting most community members. The principle of community immunity applies to control of a ...

  16. The effects of a 10% soybean oil emulsion on lymphocyte transformation.

    Science.gov (United States)

    Ota, D M; Copeland, E M; Corriere, J N; Richie, E R; Jacobson, K; Dudrick, S J

    1978-05-01

    Free essential fatty acids (EFA) are reported to suppress cell-mediated immunity. Because Intralipid contains a high concentration of esterified EFA, the effects of this emulsion on in vitro lymphocyte transformation were studied. Intralipid concentrations of 11.5, 115, and 230 mg% in lymphocyte cultures increased phytohemagglutinin (PHA) stimulation by an average of 8.2% (not significant [NS]), 18.1% (p stimulation in lymphocyte cultures by an average of 11.3 (p wells did not demonstrate allergic reactions to Intralipid. These data demonstrate that Intralipid can significantly increase the mitogenic response of human thymic lymphocytes and the antigenic response of human lymphocytes, in vitro. PMID:575908

  17. FOXP3-specific immunity

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2013-01-01

    Forkhead box P3 (FOXP3)-specific cytotoxic CD8(+) T cells are present among human peripheral blood mononuclear cells (PBMCs), especially in cancer patients. Such T lymphocytes are able not only to specifically recognize dendritic cells (DCs) that have been exposed to recombinant FOXP3 and...... regulatory T cells, but also to kill FOXP3(+) malignant T cells. The natural occurrence of FOXP3-specific cytotoxic T lymphocytes among human PBMCs suggests a general role for these cells in the complex network of immune regulation....

  18. Normal lymphocyte immunophenotype in an elderly population

    Directory of Open Access Journals (Sweden)

    Sâmia Macedo Queiroz Mota Castellão Tavares

    2014-06-01

    Full Text Available OBJECTIVE: The aim of this work was to evaluate the lymphocyte immunophenotype in an elderly population.METHODS: This study enrolled 35 over 60-year-old volunteers and a control group composed of 35 young adults. The study included elderly without diseases that might affect the functioning of the immune system. These individuals were consulted by doctors and after a physical examination, laboratory tests were performed using a Beckman Coulter (r flow cytometer. The GraphPad Prism computer program was employed for statistical analysis with the level of significance being set for p-values <0.05.RESULTS: There is a statistically significant reduction in the number of lymphocytes (CD8 +, CD2 + and CD3 + cells in the elderly compared to young adults. These low rates are explained by changes attributed to aging and may be partly responsible for the reduction in the cellular immune response, lower proliferative activity and the low cytotoxicity of lymphocytes.CONCLUSION: These parameters showed greater impairment of adaptive immunity in the elderly population and can therefore explain the greater fragility of the aged body to developing diseases.

  19. The gut microbiome as a target for regulatory T cell-based immunotherapy: induction of regulatory lymphocytes by oral administration of anti-LPS enriched colostrum alleviates immune mediated colitis

    OpenAIRE

    Yaʼacov, Ami Ben; Lichtenstein, Yoav; Zolotarov, Lidya; Ilan, Yaron

    2015-01-01

    Background Gut-derived bacterial endotoxin is an important cofactor in the pathogenesis of IBD. Regulatory T cells (Tregs) are essential for maintenance of peripheral tolerance and can prevent and alleviate IBD. To determine the immune modulatory effect of anti-LPS enriched hyperimmune colostrum, its ability to induce Tregs and alleviate immune mediated colitis. Methods Immune-mediated colitis was induced in mice by intra-colonic instillation of Trinitrobenzene Sulfonate (TNBS). Four groups o...

  20. Mitochondrial apoptosis of lymphocyte is induced in type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Xu Hui; Chen Yanbo; Li Yanxiang; Xia Fangzhen; Han Bing; Zhang Huixin; Zhai Hualing

    2014-01-01

    Background Lymphocyte function and homeostasis is associated with immune defence to infection.Apoptosis of lymphocytes might be a considerably important component which has an impact on immunity to infections in people with hyperglycemia.The aim of this study was to explore the mitochondrial apoptosis pathway of lymphocyte in diabetic patients.Methods Sixty patients with type 2 diabetes mellitus and fifty healthy volunteers were included in this study.Annexin V and propidiumiodide (Pl) were joined in the isolated lymphocytes and the rate of lymphocyte apoptosis was calculated with flow cytometry.Observation of the lymphocytes was done using transmission electron microscopy; mitochondria had been extracted and then mitochondrial membrane potential (MMP) was detected to assess mitochondrial function; the mRNA level of Bcl-2,cytochrome c (Cyt-C),caspase-9 and caspase-3 were analyzed by real-time reverse transcriptionpolymerase chain reaction (RT-PCR).Results Apoptosis rate of lymphocyte was significantly higher in diabetic group than that in normal control group (P <0.05).Transmission electron microscopy showed lymphocyte shrinkage and breakage,chromatin condensation and less mitochondria; a fall in MMP levels was also evident; Bcl-2 concentration was reduced and the expressions of caspase-9,caspase-3 and Cyt-C were elevated (P <0.05) in diabetic patients.Conclusions The rate of lymphocyte apoptosis was significantly higher in type 2 diabetic patients than that in normal population.Mitochondrial apoptosis pathway may play a very important role in decreasing function of lymphocyte in diabetes.

  1. The determination of lymphocyte transformation in patients of various diseases

    International Nuclear Information System (INIS)

    The synthesis of DNA, RNA and protein during the transformation of human lymphocytes induced by mitogen PHA and LPS was investigated by quantitation of 3H-TdR, 14C-UR and 14C-valine incorporation method. 1666 tests were carried out in patients with various diseases and 424 tests in normal subjects. It was found that immunocompetence was closely related with the progress and prognosis in patients with leukemia. Impairment of the cell-mediated immunity in patients with squamous cell carcinoma and with encephlitis was observed. There was no difference in immunity between patients with adenocarcinoma and the normal subjects. The ionizing irradiation mainly exerts its effect on cell-mediated immunity. The cell-mediated immunity was found to be impaired while the humoral immune regulation was enhanced in tuberculosis and leprosy, indicating that these diseases were caused by impairment of cell-mediated immunity. Both humoral and cell-mediated immunity return to normal levels at convalescence. The uptake of 14C-UR by lymphocytes in patients with hepatitis increased significantly. Lymphocytes reactivity was elevated in patients with vernal conjunctivities and normal in patients with uveitis. Low reactivity was observed in patients with keratitis. The immunity in various diseases was discussed

  2. Transformation delay of lymphocytes in patients undergoing radiation therapy

    International Nuclear Information System (INIS)

    Two types of assay systems to measure the effect of radiation on immune competence are described. The first, transformation, is measured by blast formation or uptake and incorporation of tritiated thymidine by lymphocytes. This measure is affected by a number of known cell responses to radiation such as division delay and delay in DNA synthesis. The second, called Bactec, is designed to measure lymphocyte metabolic activity. Data gathered on 37 patients with lung cancer show that the Bactec system provides a better index of the patient's immune status before and after radiation therapy

  3. Role of interferon in lymphocyte recruitment into the skin

    International Nuclear Information System (INIS)

    Large numbers of lymphocytes are recruited from the blood into sites of cutaneous DTH reactions. Our goal was to investigate the factors controlling this recruitment. 111In-labeled peritoneal exudate lymphocytes were injected iv and the accumulation of these cells in skin sites injected with a variety of stimuli, was used to measure lymphocyte recruitment in rats. Large numbers of lymphocytes migrated into vaccinia- and KLH-injected sites in sensitized animals, but only into the viral and not the KLH lesions in non-immune animals. Lymphocytes also migrated efficiently into sites injected with the alpha-interferon (IFN) inducers, uv-inactivated vaccinia virus and poly I:C, as well as into sites injected with IFN. In each case there was a dose-response relationship. Analysis of the kinetics of lymphocyte recruitment demonstrated that the peak rate of migration occurred most rapidly after the injection of IFN, later after poly I:C, and was slowest to be reached after vaccinia virus. Rabbit anti-IFN blocked the recruitment of lymphocytes by uv-inactivated vaccinia and by IFN. Histologically, all of these sites demonstrated a dense mononuclear cell infiltrate in the dermis. It is suggested that IFN may be an important mediator in the recruitment of lymphocytes into inflammatory reactions

  4. Imaging T-lymphocytes in inflammatory diseases: a nuclear medicine approach

    International Nuclear Information System (INIS)

    Increasing interest and research efforts have been made in search of specific radiolabelled probes for imaging different immune cells (including T-lymphocytes) in inflammation and infection. This has led to early detection of lymphocyte infiltration, and the deepening of our understanding of pathogenesis of immune mediated diseases. In-vivo imaging of T-lymphocytes with radiolabelled specific probes may provide an important piece of information about inflammatory lesions, which could be very important to understand the molecular mechanism of action of any drug and/or their effect on the microenvironment of the immune system of the body. The present review focuses on radiolabelled T-lymphocytes and different monoclonal antibodies, peptides, cytokines, chemokine used for scintigraphic imaging of T-lymphocytes and their subsets

  5. Changes in gravity inhibit lymphocyte locomotion through type I collagen

    Science.gov (United States)

    Pellis, N. R.; Goodwin, T. J.; Risin, D.; McIntyre, B. W.; Pizzini, R. P.; Cooper, D.; Baker, T. L.; Spaulding, G. F.

    1997-01-01

    Immunity relies on the circulation of lymphocytes through many different tissues including blood vessels, lymphatic channels, and lymphoid organs. The ability of lymphocytes to traverse the interstitium in both nonlymphoid and lymphoid tissues can be determined in vitro by assaying their capacity to locomote through Type I collagen. In an attempt to characterize potential causes of microgravity-induced immunosuppression, we investigated the effects of simulated microgravity on human lymphocyte function in vitro using a specialized rotating-wall vessel culture system developed at the Johnson Space Center. This very low shear culture system randomizes gravitational vectors and provides an in vitro approximation of microgravity. In the randomized gravity of the rotating-wall vessel culture system, peripheral blood lymphocytes did not locomote through Type I collagen, whereas static cultures supported normal movement. Although cells remained viable during the entire culture period, peripheral blood lymphocytes transferred to unit gravity (static culture) after 6 h in the rotating-wall vessel culture system were slow to recover and locomote into collagen matrix. After 72 h in the rotating-wall vessel culture system and an additional 72 h in static culture, peripheral blood lymphocytes did not recover their ability to locomote. Loss of locomotory activity in rotating-wall vessel cultures appears to be related to changes in the activation state of the lymphocytes and the expression of adhesion molecules. Culture in the rotating-wall vessel system blunted the ability of peripheral blood lymphocytes to respond to polyclonal activation with phytohemagglutinin. Locomotory response remained intact when peripheral blood lymphocytes were activated by anti-CD3 antibody and interleukin-2 prior to introduction into the rotating-wall vessel culture system. Thus, in addition to the systemic stress factors that may affect immunity, isolated lymphocytes respond to gravitational changes

  6. An immune based dynamic intrusion detection model

    Institute of Scientific and Technical Information of China (English)

    LI Tao

    2005-01-01

    With the dynamic description method for self and antigen, and the concept of dynamic immune tolerance for lymphocytes in network-security domain presented in this paper, a new immune based dynamic intrusion detection model (Idid) is proposed. In Idid, the dynamic models and the corresponding recursive equations of the lifecycle of mature lymphocytes, and the immune memory are built. Therefore, the problem of the dynamic description of self and nonself in computer immune systems is solved, and the defect of the low efficiency of mature lymphocyte generating in traditional computer immune systems is overcome. Simulations of this model are performed, and the comparison experiment results show that the proposed dynamic intrusion detection model has a better adaptability than the traditional methods.

  7. In vitro assessment of humoral immunity following exposure to heavy metals.

    OpenAIRE

    Koller, L D

    1982-01-01

    The immune system of animals and man is extremely complex. This report will discuss the effect metals has on one segment of the immune system; that is, humoral immunity. Humoral immunity is essentially the production of antibody in response to an antigen. The B-lymphocyte is the primary cell responsible for producing antibody. However, this cell is regulated by T-lymphocytes and macrophages. Many methods are available to assess humoral immune responses. A multitude of immunoassays have been d...

  8. Lymphocyte Functions in Space - Related Conditions

    Science.gov (United States)

    Risin, D.; Sundaresan, A.; Pellis, N. R.; Davson, David L. (Technical Monitor)

    1999-01-01

    Our previous studies showed that modeled (MMG) and true (STS-54 and STS-56) microgravity (MG) inhibit human lymphocyte locomotion. MMG also suppresses polyclonal and antigen-specific lymphocyte activation. Analysis of the relationship between activation deficits and the loss of locomotion in MG suggested a fundamental defect in signal transduction mechanism localized either at the PKC level or upstream at the cell membrane. FACS analysis of the expression of PKC isoforms in PBMC revealed that MMG selectively inhibits the PKC isoforms expression. The decrease was most prominent in PKC epsilon, less obvious in PKC delta and almost marginal and insignificant in PKC alpha. Western blot analysis confirmed these results (PKC epsilon protein expression was downregulated at 24, 72 and 96 hours in MG). We also found a decrease in PKC epsilon mRNA expression. MMG inhibited programmed cell death (PCD) in lymphocytes. Inhibition was observed in two types of experiments: 1) when PCD was induced by gamma-radiation of PBMC, and 2) when PCD in activated T cells was triggered by PHA-M or PMA + ionomycin restimulation. The established direct effects of MG on signal transduction mechanisms as well as on PCD in lymphocytes could contribute to the impairment of the immunity in space.

  9. Apoptosis signaling pathways and lymphocyte homeostasis

    Institute of Scientific and Technical Information of China (English)

    Guangwu Xu; Yufang Shi

    2007-01-01

    It has been almost three decades since the term "apoptosis" was first coined to describe a unique form of cell death that involves orderly, gene-dependent cell disintegration. It is now well accepted that apoptosis is an essential life process for metazoan animals and is critical for the formation and function of tissues and organs. In the adult mammalian body, apoptosis is especially important for proper functioning of the immune system. In recent years, along with the rapid advancement of molecular and cellular biology, great progress has been made in understanding the mechanisms leading to apoptosis. It is generally accepted that there are two major pathways of apoptotic cell death induction: extrinsic signaling through death receptors that leads to the formation of the death-inducing signaling complex (DISC), and intrinsic signaling mainly through mitochondria which leads to the formation of the apoptosome. Formation of the DISC or apoptosome, respectively, activates initiator and common effector caspases that execute the apoptosis process. In the immune system, both pathways operate; however, it is not known whether they are sufficient to maintain lymphocyte homeostasis. Recently, new apoptotic mechanisms including caspase-independent pathways and granzyme-initiated pathways have been shown to exist in lymphocytes. This review will summarize our understanding of the mechanisms that control the homeostasis of various lymphocyte populations.

  10. Comparative immune systems in animals.

    Science.gov (United States)

    Yuan, Shaochun; Tao, Xin; Huang, Shengfeng; Chen, Shangwu; Xu, Anlong

    2014-02-01

    Animal immune systems can be classified into those of innate immunity and those of adaptive immunity. It is generally thought that the former are universal for all animals and depend on germline-encoded receptors that recognize highly conserved pathogen-associated molecular patterns (PAMPs), whereas the latter are vertebrate specific and are mediated primarily by lymphocytes bearing a unique antigen receptor. However, novel adaptive or adaptive-like immunities have been found in invertebrates and jawless vertebrates, and extraordinarily complex innate immunities, created through huge expansions of many innate gene families, have recently been found in the cephalochordate amphioxus and the echinoderm sea urchin. These studies not only inspire immunologists to seek novel immune mechanisms in invertebrates but also raise questions about the origin and evolution of vertebrate immunities. PMID:25384142

  11. Diversity, function, and transcriptional regulation of gut innate lymphocytes

    OpenAIRE

    Rankin, Lucille; Groom, Joanna; Mielke, Lisa A.; Seillet, Cyril; Belz, Gabrielle T.

    2013-01-01

    The innate immune system plays a critical early role in host defense against viruses, bacteria, and tumor cells. Until recently, natural killer (NK) cells and lymphoid tissue inducer (LTi) cells were the primary members of the innate lymphocyte family: NK cells form the front-line interface between the external environment and the adaptive immune system, while LTi cells are essential for secondary lymphoid tissue formation. More recently, it has become apparent that the composition of this fa...

  12. Taurine and proliferation of lymphocytes in physically restrained rats

    OpenAIRE

    Fazzino Fili; Obregón Francisco; Lima Lucimey

    2010-01-01

    Abstract Background Taurine is present in lymphocytes and seems to modulate certain immune cell functions. Among the effects of taurine on these cells are protection against antioxidants and regulation of inflammatory aspects of the immune response. Stress affects antigen presentation, traffic and proliferation of leukocytes, as well as antibody and cytokine secretion. The purposes of this study were to explore the possible direct effects of taurine concentrations on lymphoproliferation and i...

  13. Measles immune suppression: lessons from the macaque model.

    Directory of Open Access Journals (Sweden)

    Rory D de Vries

    Full Text Available Measles remains a significant childhood disease, and is associated with a transient immune suppression. Paradoxically, measles virus (MV infection also induces robust MV-specific immune responses. Current hypotheses for the mechanism underlying measles immune suppression focus on functional impairment of lymphocytes or antigen-presenting cells, caused by infection with or exposure to MV. We have generated stable recombinant MVs that express enhanced green fluorescent protein, and remain virulent in non-human primates. By performing a comprehensive study of virological, immunological, hematological and histopathological observations made in animals euthanized at different time points after MV infection, we developed a model explaining measles immune suppression which fits with the "measles paradox". Here we show that MV preferentially infects CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, resulting in high infection levels in these populations. After the peak of viremia MV-infected lymphocytes were cleared within days, followed by immune activation and lymph node enlargement. During this period tuberculin-specific T-lymphocyte responses disappeared, whilst strong MV-specific T-lymphocyte responses emerged. Histopathological analysis of lymphoid tissues showed lymphocyte depletion in the B- and T-cell areas in the absence of apoptotic cells, paralleled by infiltration of T-lymphocytes into B-cell follicles and reappearance of proliferating cells. Our findings indicate an immune-mediated clearance of MV-infected CD45RA(- memory T-lymphocytes and follicular B-lymphocytes, which causes temporary immunological amnesia. The rapid oligoclonal expansion of MV-specific lymphocytes and bystander cells masks this depletion, explaining the short duration of measles lymphopenia yet long duration of immune suppression.

  14. 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)

  15. Lymphocyte transformation in presumed ocular histoplasmosis

    International Nuclear Information System (INIS)

    Lymphocytes from individuals with inactive macular disciform lesions of presumed ocular histoplasmosis challenged with three histoplasmin antigens incorporated tritiated thymidine at a significantly higher rate than histoplasmin-stimulated lymphocytes of matched control and peripheral scar groups. This finding is consistent with the etiologic association of the disciform ocular syndrome and previous systemic infection with Histoplasma capsulatum. The disciform group had a higher mean response than the other two groups to pokeweed mitogen but not to phytohemagglutinin and had higher mean counts per minute to the specific antigens Toxoplasma gondii, Blastomyces dermatitidis, Cryptococcus neoformans, Mycobacterium tuberculosis, M battery, and M gaus, but not to Candida albicans. These data would suggest that individuals with the disciform lesion of presumed ocular histoplasmosis have a hyperreactive cellular immune response; this response may play an important role in the development of the disciform

  16. Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

    Institute of Scientific and Technical Information of China (English)

    Ch(a)vez-Gal(a)n L; Arenas-Del Angel MC; Zenteno E; Ch(a)vez R; Lascurain R

    2009-01-01

    One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer (NK) cells and CD8+T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor (TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lyric molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis.

  17. Asymmetric Cell Division in T Lymphocyte Fate Diversification.

    Science.gov (United States)

    Arsenio, Janilyn; Metz, Patrick J; Chang, John T

    2015-11-01

    Immunological protection against microbial pathogens is dependent on robust generation of functionally diverse T lymphocyte subsets. Upon microbial infection, naïve CD4(+) or CD8(+) T lymphocytes can give rise to effector- and memory-fated progeny that together mediate a potent immune response. Recent advances in single-cell immunological and genomic profiling technologies have helped elucidate early and late diversification mechanisms that enable the generation of heterogeneity from single T lymphocytes. We discuss these findings here and argue that one such mechanism, asymmetric cell division, creates an early divergence in T lymphocyte fates by giving rise to daughter cells with a propensity towards the terminally differentiated effector or self-renewing memory lineages, with cell-intrinsic and -extrinsic cues from the microenvironment driving the final maturation steps. PMID:26474675

  18. Locomotion in Lymphocytes is Altered by Differential PKC Isoform Expression

    Science.gov (United States)

    Sundaresan, A.; Risin, D.; Pellis, N. R.

    1999-01-01

    Lymphocyte locomotion is critical for proper elicitation of the immune response. Locomotion of immune cells via the interstitium is essential for optimal immune function during wound healing, inflammation and infection. There are conditions which alter lymphocyte locomotion and one of them is spaceflight. Lymphocyte locomotion is severely inhibited in true spaceflight (true microgravity) and in rotating wall vessel culture (modeled microgravity). When lymphocytes are activated prior to culture in modeled microgravity, locomotion is not inhibited and the levels are comparable to those of static cultured lymphocytes. When a phorbol ester (PMA) is used in modeled microgravity, lymphocyte locomotion is restored by 87%. This occurs regardless if PMA is added after culture in the rotating wall vessel or during culture. Inhibition of DNA synthesis also does not alter restoration of lymphocyte locomotion by PMA. PMA is a direct activator of (protein kinase C) PKC . When a calcium ionophore, ionomycin is used it does not possess any restorative properties towards locomotion either alone or collectively with PMA. Since PMA brings about restoration without help from calcium ionophores (ionomycin), it is infer-red that calcium independent PKC isoforms are involved. Changes were perceived in the protein levels of PKC 6 where levels of the protein were downregulated at 24,72 and 96 hours in untreated rotated cultures (modeled microgravity) compared to untreated static (1g) cultures. At 48 hours there is an increase in the levels of PKC & in the same experimental set up. Studies on transcriptional and translational patterns of calcium independent isoforms of PKC such as 8 and E are presented in this study.

  19. Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2015-11-10

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  20. LYRA, a webserver for lymphocyte receptor structural modeling

    DEFF Research Database (Denmark)

    Schantz Klausen, Michael; Anderson, Mads Valdemar; Jespersen, Martin Closter;

    2015-01-01

    The accurate structural modeling of B- and T-cell receptors is fundamental to gain a detailed insight in the mechanisms underlying immunity and in developing new drugs and therapies. The LYRA (LYmphocyte Receptor Automated modeling) web server (http://www.cbs.dtu.dk/services/LYRA/) implements a...

  1. TNF-alpha, leptin, and lymphocyte function in human aging

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.;

    2000-01-01

    Aging is associated with increased inflammatory activity and concomitant decreased T cell mediated immune responses. Leptin may provide a link between inflammation and T cell function in aging. The aim of the study was to investigate if plasma levels of tumor necrosis factor (TNF)-alpha were asso...... and lymphocyte activation in vivo. These associations do not seem to involve leptin....

  2. 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...

  3. Immunization with a Circumsporozoite Epitope Fused to Bordetella pertussis Adenylate Cyclase in Conjunction with Cytotoxic T-Lymphocyte-Associated Antigen 4 Blockade Confers Protection against Plasmodium berghei Liver-Stage Malaria

    Czech Academy of Sciences Publication Activity Database

    Tartz, S.; Kamanová, Jana; Šimšová, Marcela; Šebo, Peter; Bolte, S.; Heussler, V.; Fleischer, B.; Jacobs, T.

    2006-01-01

    Roč. 74, č. 4 (2006), s. 2277-2285. ISSN 0019-9567 R&D Projects: GA AV ČR IBS5020311 Institutional research plan: CEZ:AV0Z50200510 Keywords : plasmodium berghei * immunity * malaria Subject RIV: EE - Microbiology, Virology Impact factor: 4.004, year: 2006

  4. Stages of Chronic Lymphocytic Leukemia

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...

  5. What Is Acute Lymphocytic Leukemia (ALL)?

    Science.gov (United States)

    ... White blood cells help the body fight infections. Lymphocytes These are the main cells that make up ... B cells) and T lymphocytes (T cells). B lymphocytes: B lymphocytes protect the body from invading germs ...

  6. Effect of chronic low level radiation on lectin-induced lymphocyte transformation

    International Nuclear Information System (INIS)

    As part of a comprehensive study of the effect of chronic irradiation on leukemogenesis, we have assessed the immune status of dogs subjected to such irradiation. For this purpose, we found that the whole blood lymphocyte stimulation test (WB/LST) was a more sensitive test and required much less blood. Radioresistant populations were observed. PHA-stimulated lymphocytes showed a profound reduction in response whereas the con-A-stimulated lymphocytes did not exhibit any changes. In dogs showing severe aplastic anemia, the con-A-stimulated lymphocytes were also affected. This dichotomy of immunologic response provides a radionale to explain radiation survival of specific individuals

  7. Cytotoxic T lymphocytes

    OpenAIRE

    Hirohashi, Yoshihiko; Torigoe, Toshihiko; Inoda, Satoko; Morita, Rena; Kochin, Vitaly; Sato, Noriyuki

    2012-01-01

    Cancer stem cells (CSCs)/cancer-initiating cells (CICs) are characterized as a small population of cancer cells that have high tumor-initiating ability. CSCs/CICs are resistant to several cancer therapies, and eradication of CSCs/CICs is essential to cure cancer. How can we eradicate CSCs/CICs? Cytotoxic T lymphocytes (CTLs) might be a promising answer.

  8. [Effect of lentinan against immunosuppression of lymphocytes cultured in simulated microgravity environment].

    Science.gov (United States)

    Hao, Tong; Wang, Yan-Meng; Li, Jun-Jie; Du, Zhi-Yan; Duan, Cui-Mi; Wang, Chang-Yong; Song, Jing-Ping; Wang, Lin-Jie; Li, Ying-Hui; Wang, Yan

    2012-02-01

    This study was aimed to evaluate the effect of lentinan on the immune function of splenic lymphocytes in rotary cell culture system (RCCS) microgravity environment. The splenic lymphocytes from mice were separated and cultured in the normal gravity and the microgravity environments. The cells were treated with lentinan solution (0, 10, 20 and 40 µg/ml). After incubated with lentinan for indicated times (24, 48 and 72 h), the cell proliferation, secretion of cytokine and the expression of cell surface markers were detected by MTT method, ELISA and flow cytometry respectively. The results indicated that lentinan of above mentioned concentrations did not obviously promote the lymphocyte proliferation, but increased the secretion of IL-2 and IFN-γ and enhanced the expression of lymphocyte surface markers CD4 and CD8 in microgravity environment. It is concluded that lentinan has the ability to enhance the lymphocyte immune function in microgravity environment. PMID:22391193

  9. Expression profiles of the immune genes CD4, CD8β, IFNγ, IL-4, IL-6 and IL-10 in mitogen-stimulated koala lymphocytes (Phascolarctos cinereus) by qRT-PCR

    OpenAIRE

    Iona E. Maher; Joanna E. Griffith; Quintin Lau; Thomas Reeves; Damien P. Higgins

    2014-01-01

    Investigation of the immune response of the koala (Phascolarctos cinereus) is needed urgently, but has been limited by scarcity of species-specific reagents and methods for this unique and divergent marsupial. Infectious disease is an important threat to wild populations of koalas; the most widespread and important of these is Chlamydial disease, caused by Chlamydia pecorum and Chlamydia pneumoniae. In addition, koala retrovirus (KoRV), which is of 100% prevalence in northern Australia, has b...

  10. CD4+ T-lymphocyte telomere length is related to fibrosis stage, clinical outcome and treatment response in chronic hepatitis C virus infection.

    OpenAIRE

    FLETCHER, JEAN

    2010-01-01

    PUBLISHED BACKGROUND & AIMS: Increasing age is associated with impaired immune function and in chronic HCV infection specifically, with progressive fibrosis, liver failure, HCC and impaired responses to antiviral therapy. T-lymphocyte telomere length declines with age. We hypothesised that shorter T-lymphocyte telomere length would be associated with poor clinical outcome in HCV infection. METHODS: Circulating T-lymphocyte telomere length, an objective measure of immune senescence, was...

  11. Scaling Aspects of Lymphocyte Trafficking

    OpenAIRE

    Perelson, Alan S.; Wiegel, Frederik W.

    2008-01-01

    We consider the long lived pool of B and T cells that recirculate through blood, tissues and the lymphatic system of an animal with body mass M. We derive scaling rules (allometric relations) for: (1) the rate of production of mature lymphocytes; (2) the accumulation of lymphocytes in the tissues; (3) the flux of lymphocytes through the lymphatic system; (4) the number of lymph nodes, (5) the number of lymphocytes per clone within a lymph node, and (6) the total number of lymphocytes within a...

  12. Immune System

    Science.gov (United States)

    ... Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  13. Immune system simulation online

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Lund, Ole; Castiglione, Filippo

    2011-01-01

    MOTIVATION: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way. RESULTS: We have equipped an agent-based model of the immune system with immuno......-specific scoring matrices based on information from known HLA epitopes prediction tools, and TCR binding to HLA–peptide complex calculated as the averaged sum of a residue–residue contact potential. These steps are executed for all lymphocytes agents encountering the antigen in a wide-reaching Monte Carlo......-informatics methods to allow the simulation of the cardinal events of the antigenic recognition, going from single peptides to whole proteomes. The recognition process accounts for B cell-epitopes prediction through Parker-scale affinity estimation, class I and II HLA peptide prediction and binding through position...

  14. Prognostic impact of lymphocytes in soft tissue sarcomas.

    Directory of Open Access Journals (Sweden)

    Sveinung W Sorbye

    Full Text Available PURPOSE: The purpose of this study was to clarify the prognostic significance of lymphocyte infiltration in soft tissue sarcomas (STS. Prognostic markers in potentially curable STS should guide therapy after surgical resection. The immune status at the time of resection may be important, but the prognostic significance of tumor infiltrating lymphocytes is controversial as the immune system has conflicting roles during cancer development. EXPERIMENTAL DESIGN: Tissue microarrays from 249 patients with STS were constructed from duplicate cores of viable and representative neoplastic tumor areas. Immunohistochemistry was used to evaluate the CD3+, CD4+, CD8+, CD20+ and CD45+ lymphocytes in tumors. RESULTS: In univariate analyses, increased numbers of CD4+ (P = 0.008 and CD20+ (P = 0.006 lymphocytes in tumor correlated significantly with an improved disease-specific survival (DSS in patients with wide resection margins (n = 108. In patients with non-wide resection margins (n = 141 increased numbers of CD3+ (P = 0.028 lymphocytes in tumor correlated significantly with shorter DSS. In multivariate analyses, a high number of CD20+ lymphocytes (HR = 5.5, CI 95%  = 1.6-18.6, P = 0.006 in the tumor was an independent positive prognostic factor for DSS in patients with wide resections margins. CONCLUSIONS: High density of CD20+ lymphocytes in STS with wide resection margins is an independent positive prognostic indicator for these patients. Further research is needed to define if CD20+ cells can modify tumors in a way that reduces disease progression and metastatic potential.

  15. Functional inactivation of lymphocytes by methylene blue with visible light.

    Science.gov (United States)

    Zhang, Bo; Cheng, Zhenzhen; Mo, Qin; Wang, Li; Wang, Xun; Wu, Xiaofei; Jia, Yao; Huang, Yuwen

    2015-10-01

    Transfusion of allogeneic white blood cells (WBCs) may cause adverse reactions in immunocompromised recipients, including transfusion-associated graft-versus-host disease (TA-GVHD), which is often fatal and incurable. In this study, the in vitro effect of methylene blue with visible light (MB + L) treatment on lymphocyte proliferation and cytokine production was measured to investigate whether MB + L can be used to prevent immune reactions that result from transfused lymphocytes. WBCs and 3 μM of MB were mixed and transferred into medical PVC bags, which were then exposed to visible light. Gamma irradiation was conducted as a parallel positive control. The cells without treatment were used as untreated group. All the groups were tested for the ability of cell proliferation and cytokine production upon stimulation. After incubation with mitogen phytohemagglutinin (PHA) or plate-bound anti-CD3 plus anti-CD28, the proliferation of MB + L/gamma-irradiation treated lymphocytes was significantly inhibited (P cells (73.77% ± 28.75% vs. 44.72% ± 38.20%). MB + L treated cells incubated up to 7 days with PHA also showed no significant proliferation. The levels of TNF-α, IFN-γ, IL-6, IL-8, IL-10 and IL-1β present in the supernatant of MB + L treated lymphocytes upon stimulation were significantly lower than those of untreated lymphocytes. These results demonstrated that MB + L treatment functionally and irreversibly inactivated lymphocytes by inhibiting lymphocyte proliferation and the production of cytokines. MB + L treatment might be a promising method for the prevention of adverse immune responses caused by WBCs. PMID:26295729

  16. Microgravity and Cellular Consequences in Lymphocyte Function

    Science.gov (United States)

    Pellis, Neal R.; Sundaresan, Alamelu

    2004-01-01

    Mammalian cells adapt to the environment of low gravity and express a series of responses, some possibly from direct effects on cells and others based on environmental conditions created by microgravity. Human lymphocytes in microgravity culture are functionally diminished in activation and locomotion. Both processes are integral to optimal immune response to fight pathogens. The NASA Rotating-wall vessel (RWV) is a well-accepted analog for microgravity culture on the ground. Gene array experiments and immunoblotting identified upstream events in human lymphocytes adapting to microgravity analog culture. Microgravity induces selective changes, many of which are cell membrane related. Results showed that upstream of PKC in the T cell activation cascade, PLC-gamma and LAT are significantly diminished. ZAP 70 which controls LAT activation is also down regulated in modeled microgravity. Thus events governing cell shape might warrant attention in microgravity conditions. The goal of this study is to delineate response suites that are consequential, direct or indirect effects of the microgravity environment and which of these are essential to lymphocytes

  17. Innate immunity in the pathogenesis of psoriasis.

    LENUS (Irish Health Repository)

    Sweeney, Cheryl M

    2011-12-01

    Psoriasis is a common, immune-mediated inflammatory skin disorder. T helper(h)1 and Th17 lymphocytes contribute to the pathogenesis of psoriasis through the release of inflammatory cytokines that promote further recruitment of immune cells, keratinocyte proliferation and sustained inflammation. The innate immune system is the first line of defence against infection and plays a crucial role in the initiation of the adaptive immune response. The presence of innate immune cells and their products in psoriatic skin plaques suggests a role for innate immunity in this disease. In addition, the innate immune system can direct the development of pathogenic Th cells in psoriasis. In this article, we will summarise the role of the innate immune system in psoriasis with particular emphasis on the role of cytokines, signalling pathways and cells of the innate immune system.

  18. Sequence conservation of subdominant HLA-A2-binding CTL epitopes in HIV-1 clinical isolates and CD8+ T-lymphocyte cross-recognition may explain the immune reaction in infected individuals

    DEFF Research Database (Denmark)

    Thorn, Mette; Tang, Sheila; Therrien, Dominic;

    2007-01-01

    genome sequenced HIV-1 from 11 HLA-A2(+) patients to examine the sequence variation of these natural epitopes and compared them with the patient's CD8(+) T-cell recall response. Often the epitope was conserved but only a few patients showed a CD8(+) T-cell recall response. This infrequent targeting may...... be explained by immune subdominance. CD8(+) T-cell recall response to a natural epitope could be measured despite sequence differences in the patient's virus. T-cell cross-reaction between such variants could be demonstrated in HLA-A2 transgenic mice. Nine infrequently targeted but conserved or cross...

  19. Lymphocyte proliferation in Peyer's patches of Giardia muris-infected mice.

    OpenAIRE

    Hill, D R

    1990-01-01

    Gastrointestinal immune events in giardiasis are important in controlling infection. In this study, Peyer's patch lymphocytes from mice infected with Giardia muris developed specific, proliferative responses to G. muris antigen. This proliferation correlated with clearance of infection. Further understanding of the gut immune response will be helpful in developing immunoprophylactic strategies in the control of giardiasis.

  20. T Lymphocyte Maturation Is Impaired in Healthy Young Individuals Carrying Trisomy 21 (Down Syndrome)

    Science.gov (United States)

    Guazzarotti, Laura; Trabattoni, Daria; Castelletti, Eleonora; Boldrighini, Benedetta; Piacentini, Luca; Duca, Piergiorgio; Beretta, Silvia; Pacei, Michela; Caprio, Cristiana; Vigano, Alessandra; di Natale, Berardo; Zuccotti, Gian Vincenzo; Clerici, Mario

    2009-01-01

    Cytokine production, immune activation, T lymphocytes maturation, and serum IL-7 concentration were examined in 24 youngsters with Down syndrome and no acquired diseases (healthy Down syndrome [12 prepubertal, 13 pubertal]) and 42 age- and gender-matched controls (20 prepubertal, 22 pubertal). Results showed that a complex immune and impairment is…

  1. NETMHCSTAB - predicting stability of peptide-MHC-I complexes; impacts for cytotoxic T lymphocyte epitope discovery

    DEFF Research Database (Denmark)

    Jørgensen, Kasper W.; Rasmussen, Michael; Buus, Søren;

    2013-01-01

    Major histocompatibility complex class I (MHC-I) molecules play an essential role in the cellular immune response, presenting peptides to cytotoxic T lymphocytes (CTLs) allowing the immune system to scrutinize ongoing intracellular production of proteins. In the early 1990s, immunogenicity and...

  2. Intracellular modulation, extracellular disposal and serum increase of MiR-150 mark lymphocyte activation.

    Directory of Open Access Journals (Sweden)

    Paola de Candia

    Full Text Available Activated lymphocytes release nano-sized vesicles (exosomes containing microRNAs that can be monitored in the bloodstream. We asked whether elicitation of immune responses is followed by release of lymphocyte-specific microRNAs. We found that, upon activation in vitro, human and mouse lymphocytes down-modulate intracellular miR-150 and accumulate it in exosomes. In vivo, miR-150 levels increased significantly in serum of humans immunized with flu vaccines and in mice immunized with ovalbumin, and this increase correlated with elevation of antibody titers. Immunization of immune-deficient mice, lacking MHCII, resulted neither in antibody production nor in elevation of circulating miR-150. This study provides proof of concept that serum microRNAs can be detected, with minimally invasive procedure, as biomarkers of vaccination and more in general of adaptive immune responses. Furthermore, the prompt reduction of intracellular level of miR-150, a key regulator of mRNAs critical for lymphocyte differentiation and functions, linked to its release in the external milieu suggests that the selective extracellular disposal of microRNAs can be a rapid way to regulate gene expression during lymphocyte activation.

  3. 叶绿素铜钠促进再障小鼠骨髓MSC对T细胞的干预作用%Regulation of Sodium Copper Chlorophyll in Promoting Mesenchymal Stem Cells on T Lymphocytes in Immune -mediated AA Mice

    Institute of Scientific and Technical Information of China (English)

    王灵聪; 蒋慧芳; 尹利明; 魏克民

    2012-01-01

    目的:探讨叶绿素铜钠促进免疫介导再生障碍性贫血(aplastic anemia,AA)小鼠骨髓间充质干细胞(mensenchymal stem cells,MSC)对T淋巴细胞的干预作用.方法:建立免疫介导AA小鼠模型,随机分为正常对照组(N)、AA模型组(M)、环孢菌素组(Cs)、叶绿素铜钠小剂量组(X)、叶绿素铜钠中剂量组(Z)、叶绿素铜钠高剂量组(G)6组,每组6只,15日后处死,观察各组的骨髓病理,骨髓进行MSC培养,第3代MSC诱导成骨细胞,观察光镜下第2代MSC (F2MSC)、成骨细胞的形态学变化,MSC调节植物血凝素(PHA)对T淋巴细胞转化实验,ELISA检测MSC的转化生长因子(TGF-β1).结果:N、Cs、X、Z、G组的骨髓增生均比M组活跃.各组F2MSC细胞呈长梭形,第3代MSC可被诱导为成骨细胞.N、X、Z、G组的CD+25 FOXP+3明显大于M组(P<0.05).N、Cs、Z组的TGF-β1显著大于M组(P<0.05).结论:叶绿素铜钠能促进AA小鼠MSC对T淋巴细胞的干预作用.%the mice were killed after 15 days. Observe the bone marrow pathology of each group, bone marrow was given MSC culture and the third generation of MSCs were used to induce osteoblasts. The second generation of MSC ( F2MSC) and morphological changes of osteoblasts were observed under light microscope. MSC adjusted phytohemagglutinin ( PHA) on T lymphocyte transformation test and the transforming growth factor ( TGF - pi ) of MSC was measured by ELISA. Results -. The bone marrow hyperplasia were more active in the groups of N, Cs, X, Z, G than those in M group. F2MSC were e-longated spindle cells in each group. The third generation of MSC were induced into osteoblasts. The CD^and FOXP3 of N, X, Z, G groups were significantly higher than those of M group ( P < 0.05 ) . The TGF - (31 of N, Cs, Z groups were significantly higher than those of M group ( P < 0. 05 ). Conclusion: Sodium copper chlorophyll can promote MSC to regulate T lymphocytes in AA mice.

  4. A preliminary study to evaluate the immune responses induced by immunization of dogs with inactivated Ehrlichia canis organisms

    Directory of Open Access Journals (Sweden)

    Sunita Mahan

    2005-09-01

    Full Text Available Ehrlichia canis is an intracellular pathogen that causes canine monocytic ehrlichiosis. Although the role of antibody responses cannot be discounted, control of this intracellular pathogen is expected to be by cell mediated immune responses. The immune responses in dogs immunized with inactivated E. canis organisms in combination with Quil A were evaluated. Immunization provoked strong humoral and cellular immune responses, which were demonstrable by Western blotting and lymphocyte proliferation assays. By Western blotting antibodies to several immunodominant E. canis proteins were detected in serum from immunized dogs and antibody titres increased after each immunization. The complement of immunogenic proteins recognized by the antisera were similar to those recognized in serum from infected dogs. Upon challenge with live E. canis, rapid anamnestic humoral responses were detected in the serum of immunized dogs and primary antibody responses were detected in the serum from control dogs. Following immunization, a lymphocyte proliferative response (cellular immunity was detected in peripheral blood mononuclear cells (PBMNs of immunized dogs upon stimulation with E. canis antigens. These responses were absent from non-immunized control dogs until after infection with live E. canis, when antigen specific-lymphocyte proliferation responses were also detected in the PBMNs of the control dogs. It can be thus concluded that immunization against canine monocytic ehrlichiosis may be feasible. However, the immunization regimen needs to be optimized and a detailed investigation needs to be done to determine if this regimen can prevent development of acute and chronic disease.

  5. Effects of radiation therapy on T-lymphocyte subpopulations in patients with head and neck cancer

    International Nuclear Information System (INIS)

    Cellular immunity was assessed in 85 patients with head and neck cancer with monoclonal antibodies to lymphocyte surface antigens that identify total T cells, helper cells, and suppressor cells. The control group consisted of 22 healthy volunteers. Nine patients who had surgical procedures for benign diseases were also studied. Compared with the controls, the patients with cancer who received radiation therapy had a significant decrease in total lymphocytes, T cells, helper cells, suppressor cells, and decreased helper/suppressor cell ratio. Significant decreases in lymphocyte subpopulations were not detected in patients tested before treatment or in patients treated with surgery alone. The immune deficits observed were prolonged in duration, with some present in the patients studied up to 11 years after radiation therapy. This long-lasting immune depression may have relevance to tumor recurrences and second primaries in patients with head and neck cancer treated by radiation therapy and to attempts at increasing cure rates with adjuvant agents that improve immune reactivity

  6. Natural and immune cytolysis of canine distemper virus-infected target cells.

    OpenAIRE

    Shek, W R; Schultz, R D; Appel, M J

    1980-01-01

    Natural and immune cytolysis of canine distemper virus (CDV)-infected target cells in vitro is described. Lymphocytes expressing natural cytotoxicity were found in specific-pathogen-free beagle dogs and in beagle-coonhound crosses before vaccination with CDV and indefinitely after vaccination, when the ephemeral immune lymphocyte-mediated cytotoxicity (ILMC) had declined. In contrast to the natural lymphocyte-mediated cytotoxicity, the ILMC was genetically restricted, could not be blocked by ...

  7. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-02-16

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  8. Alterations in lymphocyte subset patterns and co-stimulatory molecules in patients with Alzheimer disease

    Institute of Scientific and Technical Information of China (English)

    XUE Shou-ru; XU Dong-hua; YANG Xin-xin; DONG Wan-li

    2009-01-01

    @@ Alzheimer disease (AD) is characterized by the presence of β-amyloid (Aβ) plaques in the brain.1 More evidence of inflammatory parameters, such as, complement factors, proinflammatory cytokines and lymphocytes has been found to be co-localized with Aβ plaques,1,2 The research in the past decades has demonstrated abnormalities of both the humoral and cellular immune responses, suggesting an association of immunological aberration and AD. The total percentage of lymphocytes was not found to be altered, whereas the alterations of T-cell function, differentiation and subset distribution have still been unresolved.3,4 A significantly decreased function of suppressor as well as helper T-cells and natural killer (NK) cells in AD patients has been observed. Studies on lymphocyte subpopulations showed conflicting results, while other studies could not find alterations in lymphocyte subset distribution. In the present study, we assume the immune system dysregulation depending on a defective immune response which also affects lymphocyte differentiation and subset distribution. We investigated T lymphocyte subset pattems and co-stimulatory molecules, as well as B lymphocytes and NK cells in peripheral blood of AD patients and age matched healthy controls.

  9. [Effect of anabolic steroid on immune response].

    Science.gov (United States)

    Yamagishi, H; Kobayashi, M; Konosu, H; Kurioka, H; Naito, K; Sonoyama, T; Nishimoto, T; Hashimoto, I

    1984-03-01

    Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin. PMID:6367663

  10. Immune networks: multitasking capabilities near saturation

    International Nuclear Information System (INIS)

    Pattern-diluted associative networks were recently introduced as models for the immune system, with nodes representing T-lymphocytes and stored patterns representing signalling protocols between T- and B-lymphocytes. It was shown earlier that in the regime of extreme pattern dilution, a system with NT T-lymphocytes can manage a number NB=O(NTδ) of B-lymphocytes simultaneously, with δ B = αNT, with a high degree of pattern dilution, in agreement with immunological findings. We use graph theory and statistical mechanical analysis based on replica methods to show that in the finite-connectivity regime, where each T-lymphocyte interacts with a finite number of B-lymphocytes as NT → ∞, the T-lymphocytes can coordinate effective immune responses to an extensive number of distinct antigen invasions in parallel. As α increases, the system eventually undergoes a second order transition to a phase with clonal cross-talk interference, where the system’s performance degrades gracefully. Mathematically, the model is equivalent to a spin system on a finitely connected graph with many short loops, so one would expect the available analytical methods, which all assume locally tree-like graphs, to fail. Yet it turns out to be solvable. Our results are supported by numerical simulations. (paper)

  11. Immune Dysfunction in Tourette Syndrome

    Directory of Open Access Journals (Sweden)

    Ishraga Elamin

    2013-01-01

    Full Text Available The association between immunity and neurodevelopmental disorders has been extensively investigated in autism, suggesting a potential involvement of both cellular and humoral immunity in the establishment of synaptic connectivity modulation during development. A similar link has been proposed also for Tourette syndrome (TS, a complex, multifactorial disorder, in which the interplay between genetic, environmental, hormonal and immunological factors might be relevant. Lymphocyte subpopulation analysis in TS suggests a possible systemic activation of several T- and B-cell subtypes, whereas the observed decreased numbers of T regulatory lymphocytes might predispose to autoimmunity. Genes related to both cell- and antibody-mediated immune responses may be over-expressed at specific ages in youngsters with TS. Data from cytokine measurements and transcriptomics profiles in TS patients are coherent with the systemic immune activation detected by studies on lymphocyte subpopulations. Moreover, TS patients have exhibited IgG3 and IgA dysgammaglobulinemia, which might predispose to recurrent infections and autoimmunity. To date, the association between TS and autoantibodies has not been demonstrated. Interestingly, however, there is a higher degree of maternal family history of autoimmune diseases among TS patients. Finally, TS patients could be prone to allergic illnesses (asthma, atopic dermatitis, rhinitis, conjunctivitis, but more work is needed in this area.

  12. Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise

    Science.gov (United States)

    Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

    2016-01-01

    This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90–100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important

  13. Lymphocyte Redox Imbalance and Reduced Proliferation after a Single Session of High Intensity Interval Exercise.

    Science.gov (United States)

    Tossige-Gomes, Rosalina; Costa, Karine Beatriz; Ottone, Vinícius de Oliveira; Magalhães, Flávio de Castro; Amorim, Fabiano Trigueiro; Rocha-Vieira, Etel

    2016-01-01

    This study investigated whether an acute session of high-intensity interval training (HIIT) is sufficient to alter lymphocyte function and redox status. Sixteen young healthy men underwent a HIIT session on a cycloergometer, consisting of eight bouts of 1 min at 90-100% of peak power, with 75 seconds of active recovery at 30 W between bouts. Venous blood was collected before, immediately after, and 30 minutes after the HIIT session. In response to Staphylococcus aureus superantigen B (SEB) stimulation, lymphocyte proliferation decreased and the IL-2 concentration increased after the HIIT session. However, the HIIT session had no effect on lymphocyte proliferation or IL-2 response to phytohemagglutinin stimulation. The HIIT session also induced lymphocyte redox imbalance, characterized by an increase in the concentration of thiobarbituric acid reactive substances and a decrease in the activity of the antioxidant enzyme catalase. Lymphocyte viability was not affected by the HIIT session. The frequencies of CD25+ and CD69+ T helper and B lymphocytes in response to superantigen stimulation were lower after exercise, suggesting that superantigen-induced lymphocyte activation was reduced by HIIT. However, HIIT also led to a reduction in the frequency of CD4+ and CD19+ cells, so the frequencies of CD25+ and CD69+ cells within the CD4 and CD19 cell populations were not affected by HIIT. These data indicate that the reduced lymphocyte proliferation observed after HIIT is not due to reduced early lymphocyte activation by superantigen. Our findings show that an acute HIIT session promotes lymphocyte redox imbalance and reduces lymphocyte proliferation in response to superantigenic, but not to mitogenic stimulation. This observation cannot be explained by alteration of the early lymphocyte activation response to superantigen. The manner in which lymphocyte function modulation by an acute HIIT session can affect individual immunity and susceptibility to infection is important

  14. Immunogenetic analysis of cellular interactions governing the recruitment of T lymphocytes and monocytes in lymphocytic choriomeningitis virus-induced immunopathology

    International Nuclear Information System (INIS)

    The Lyt2+ class I major histocompatibility complex (MHC)-restricted virus-immune T cells that induce murine lymphocytic choriomeningitis (LCM) are targeted onto radiation-resistant cells in the central nervous system of virus-infected mice. The use of appropriate bone marrow radiation chimeras as LCM virus-infected, (immunosuppressed recipients for immune T-cell transfer has established that, though bone marrow-derived cells can stimulate virus-specific cytotoxic T lymphocytes (CTL) in spleen, they do not reconstitute the barrier to T-cell recruitment from blood to cerebrospinal fluid. This is true for chimeras made up to 8 months previously, even though the inflammatory monocytes and macrophages in such chimeras are all of donor bone marrow origin. Radiation-resistant cells in the spleens of these chimeras are also still able to further stimulate virus-immune CTL. There is no requirement for H-2 compatibility between virus-immune T lymphocytes and secondarily recruited monocytes, or T cells of an inappropriate specificity. The key event in LCM immunopathology may thus be localization of T cells to the antigen-presenting endothelium in brain, leading to the secretion of mediators that promote the nonspecific recruitment of monocytes and other T cells

  15. Clonal expansion of renal cell carcinoma-infiltrating T lymphocytes

    DEFF Research Database (Denmark)

    Sittig, Simone; Køllgaard, Tania; Grønbæk, Kirsten;

    2013-01-01

    T lymphocytes can mediate the destruction of cancer cells by virtue of their ability to recognize tumor-derived antigenic peptides that are presented on the cell surface in complex with HLA molecules and expand. Thus, the presence of clonally expanded T cells within neoplastic lesions is an...... indication of ongoing HLA-restricted T cell-mediated immune responses. Multiple tumors, including renal cell carcinomas (RCCs), are often infiltrated by significant amounts of T cells, the so-called tumor-infiltrating lymphocytes (TILs). In the present study, we analyzed RCC lesions (n = 13) for the presence...... of expanded T-cell clonotypes using T-cell receptor clonotype mapping. Surprisingly, we found that RCCs comprise relatively low numbers of distinct expanded T-cell clonotypes as compared with melanoma lesions. The numbers of different T-cell clonotypes detected among RCC-infiltrating lymphocytes were...

  16. Actin nucleation at the centrosome controls lymphocyte polarity.

    Science.gov (United States)

    Obino, Dorian; Farina, Francesca; Malbec, Odile; Sáez, Pablo J; Maurin, Mathieu; Gaillard, Jérémie; Dingli, Florent; Loew, Damarys; Gautreau, Alexis; Yuseff, Maria-Isabel; Blanchoin, Laurent; Théry, Manuel; Lennon-Duménil, Ana-Maria

    2016-01-01

    Cell polarity is required for the functional specialization of many cell types including lymphocytes. A hallmark of cell polarity is the reorientation of the centrosome that allows repositioning of organelles and vesicles in an asymmetric fashion. The mechanisms underlying centrosome polarization are not fully understood. Here we found that in resting lymphocytes, centrosome-associated Arp2/3 locally nucleates F-actin, which is needed for centrosome tethering to the nucleus via the LINC complex. Upon lymphocyte activation, Arp2/3 is partially depleted from the centrosome as a result of its recruitment to the immune synapse. This leads to a reduction in F-actin nucleation at the centrosome and thereby allows its detachment from the nucleus and polarization to the synapse. Therefore, F-actin nucleation at the centrosome-regulated by the availability of the Arp2/3 complex-determines its capacity to polarize in response to external stimuli. PMID:26987298

  17. Vorinostat, Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-05-04

    Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  18. Systemic and Mucosal T-Lymphocyte Activation Induced by Recombinant Adenovirus Vaccines in Rhesus Monkeys▿

    OpenAIRE

    Sun, Yue; Bailer, Robert T.; Rao, Srinivas S.; Mascola, John R.; Nabel, Gary J.; Koup, Richard A.; Letvin, Norman L.

    2009-01-01

    The administration of vectors designed to elicited cell-mediated immune responses may have other consequences that are clinically significant. To explore this possibility, we evaluated T-cell activation during the first 2 months after recombinant adenovirus serotype 5 (rAd5) prime or boost immunizations in rhesus monkeys. We also evaluated the kinetics of T-lymphocyte activation in both the systemic and the mucosal compartments after rAd5 administration in monkeys with preexisting immunity to...

  19. The immune microenvironment of breast ductal carcinoma in situ.

    Science.gov (United States)

    Thompson, Elizabeth; Taube, Janis M; Elwood, Hillary; Sharma, Rajni; Meeker, Alan; Warzecha, Hind Nassar; Argani, Pedram; Cimino-Mathews, Ashley; Emens, Leisha A

    2016-03-01

    The host immune response has a key role in breast cancer progression and response to therapy. However, relative to primary invasive breast cancers, the immune milieu of breast ductal carcinoma in situ (DCIS) is less understood. Here, we profile tumor infiltrating lymphocytes and expression of the immune checkpoint ligand programmed death ligand 1 (PD-L1) in 27 cases of DCIS with known estrogen receptor (ER), progesterone receptor, and human epidermal growth factor 2 (HER-2) expression using tissue microarrays. Twenty-four cases were pure DCIS and three had associated invasive ductal carcinoma. Tumors were stained by immunohistochemistry for PD-L1, as well as the lymphocyte markers CD3, CD4, CD8, FoxP3, and CD20. The expression of PD-L1 by DCIS carcinoma cells and tumor infiltrating lymphocytes was determined, and the average tumor infiltrating lymphocytes per high power field were manually scored. None of the DCIS cells expressed PD-L1, but 81% of DCIS lesions contained PD-L1+ tumor infiltrating lymphocytes. DCIS with moderate-diffuse tumor infiltrating lymphocytes was more likely to have PD-L1+ tumor infiltrating lymphocytes (P=0.004). Tumor infiltrating lymphocytes with high levels of PD-L1 expression (>50% cells) were seen only in triple-negative DCIS (P=0.0008), and PD-L1-tumor infiltrating lymphocytes were seen only in ER+/HER-2-DCIS (P=0.12). The presence of PD-L1+ tumor infiltrating lymphocytes was associated with a younger mean patient age (P=0.01). Further characterization of the DCIS immune microenvironment may identify useful targets for immune-based therapy and breast cancer prevention. PMID:26769139

  20. Structural and functional changes in lymphocytes in microgravity

    Science.gov (United States)

    Risin, D.; Risin, S.; Ward, N.; Sundaresan, A.; Pellis, N. R.

    Impairment of the immunity in astronauts and cosmonauts even in short-term flights is a recognized risk. Long-term orbital space missions and anticipated interplanetary flights increase the concern for more pronounced effects on the immune system with potential clinical consequences. Since 1992 we are investigating the effect of modeled (MMG) and true microgravity on isolated lymphocytes in vitro. We had shown that modeled and true microgravity inhibit lymphocyte locomotion. Modeled microgravity also suppresses polyclonal and antigen-specific lymphocyte activation. At the same time polyclonal lymphocyte activation prior to exposure to MMG abrogates the MG-induced inhibition of lymphocyte locomotion. Analysis of the relationship between activation deficits and the loss of locomotion in MG suggested a fundamental defect in signal transduction mechanism that was confirmed in further studies. FACS analysis showed that MMG selectively inhibits the expression of PKC isoforms. The decrease was most prominent and substantial in PKC ɛ, less obvious in PKC δ and almost marginal and insignificant in PKC α . Downregulation of PKC isoforms δ and ɛ was proven at the mRNA level by RT-PCR and at protein level by Western blot. We had also demonstrated that MMG selectively affects not only the expression but also the cell distribution of different PKC isoforms that may contribute to the impairment of signal transduction in MG. MMG inhibits programmed cell death (PCD) in lymphocytes. Inhibition was observed in two experimental models (PCD induced by gamma-radiation in PBMC and activation-induced PCD in activated T cells after restimulation with PHA-M or PMA+ionomycin.). Comparative DNA chip analysis has demonstrated a significant difference in gene expression profiles between static and MG analog cultures of activated T cells. (Supported by NRA OLMSA-02 and NSCORT NAG5-4072 grants).

  1. Iron overload and immunity

    Institute of Scientific and Technical Information of China (English)

    Gra(c)a Porto; Maria De Sousa

    2007-01-01

    Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage.Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes,will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating how the disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.

  2. Interleukin-15 treatment induces weight loss independent of lymphocytes.

    Directory of Open Access Journals (Sweden)

    Nicole G Barra

    Full Text Available Obesity is a chronic inflammatory condition characterized by activation and infiltration of proinflammatory immune cells and a dysregulated production of proinflammatory cytokines. While known as a key regulator of immune natural killer (NK cell function and development, we have recently demonstrated that reduced expression of the cytokine Interleukin-15 (IL-15 is closely linked with increased body weight and adiposity in mice and humans. Previously, we and others have shown that obese individuals have lower circulating levels of IL-15 and NK cells. Lean IL-15 overexpressing (IL-15 tg mice had an accumulation in adipose NK cells compared to wildtype and NK cell deficient obese IL-15(-/- mice. Since IL-15 induces weight loss in IL-15(-/- and diet induced obese mice and has effects on various lymphocytes, the aim of this paper was to determine if lymphocytes, particularly NK cells, play a role in IL-15 mediated weight loss. Acute IL-15 treatment resulted in an increased accumulation of NK, NKT, and CD3(+ T cells in adipose tissue of B6 mice. Mice depleted of NK and NKT cells had similar weight loss comparable to controls treated with IL-15. Finally, IL-15 treatment induces significant weight loss in lymphocyte deficient RAG2(-/-γc(-/- mice independent of food intake. Fat pad cross-sections show decreased pad size with cytokine treatment is due to adipocyte shrinkage. These results clearly suggest that IL-15 mediates weight loss independent of lymphocytes.

  3. Protective effect of citrullus vulgaris on irradiated lymphocyte membrane ultrastructure

    International Nuclear Information System (INIS)

    Radiotherapy causes various complications including low immunity. Past research that the low immunity is due to the low amount of lymphocytes and consumption vulgaris will alleviate this problem. Based on this a study was conducted to identify vulgaris was able to produce radioprotection on the lymphocyte membrane. A total of 30 adult male Sprague-Dawley rats were used and divided into three equals groups of positive control and treatment. For seven days, positive control and negative control were force fed with normal saline of 40 ml/kg animal weight while the treatment group received 40g/kg animal weight fresh juice of citrullus vulgaris daily. After a week positive control an group were irradiated with 0.9 Gy gamma ray. Viable lymphocyte were determined using propidium iodine and acridine orange stain. Results clearly shows that positive con and treatment group were significantly different at 34 ± 3% , 80 ± 2% an 71 ± 2% respectively. SEM results shows that pores were present on the membrane of the pos while the negative control had none. Similar results were also found on the treatment group. Based on the result it had shown that citrullus vulgaris had radioprotection properties and lymphocytes were destroyed by the formation of pores on their membrane. It is very likely that the radioprotection properties could be due to the presence of antioxidants particularly vitamin A, C and lycopene. In conclusion, citrullus vulgaris could be used as a safe radioprotection agent. (Author)

  4. Changes in count and function of splenic lymphocytes from patients with portal hypertension

    Institute of Scientific and Technical Information of China (English)

    Zong-Fang Li; Shu Zhang; Gao-Bo Lv; Ying Huang; Wei Zhang; Song Ren; Jun Yang; Shuang-Suo Dang

    2008-01-01

    AIM: To investigate changes in numbers and proliferative function of splenic lymphocytes in patients with hypersplenism due to portal hypertension (PH), to provide evidence for further study of immune status of the spleen during PH.METHODS: Twelve spleens from patients with hypersplenism due to PH served as the PH group, and four spleens from cases of traumatic spleen rupture were regarded as the control group. After weighing the spleen, lymphocytes were separated and counted using a cell counting plate to calculate the lymphocyte count per gram of spleen tissue (relative quantity) and total lymphocyte count in whole spleen (absolute quantity). The immunohistochemical SP method was used to observe the density and distribution of lymphocytes in the spleen. The MTT method was used to observe changes in lymphocyte proliferative function.RESULTS: As compared to the control group, the splenic lymphocytes in the PH group showed that: (1) There was no difference in distribution but a significant decrease in density; (2) the number of lymphocytes per gram of spleen (relative quantity) decreased significantly [(0.822±0.157) × 108 vs (1.174±0.254) × 108, P < 0.01];(3) with the significant increase in the weight of the PH spleen (832.6±278.2 g vs 211.7±85.6 g, P < 0.01),the total quantity of lymphocytes (absolute quantity)increased significantly [(0.685±0.072) × 1011 vs (0.366±0.057) × 1011, P < 0.01]; and (4) the proliferative function of lymphocytes was enhanced: T lymphocytes,(0.022±0.005 vs 0.015±0.003, P < 0.05), and B lymphocytes (0.034±0.006 vs 0.023±0.001, P < 0.01).CONCLUSION: Although lymphocyte density in the spleen decreased in patients with PH, the total quantity of lymphoytes increased because spleen weight increased greatly, along with the proliferating function. With respect to changes in lymphocytes, PH spleens may still have immune function, although it may be disordered. However,complete evaluation of the immune function of the spleenin PH

  5. Mathematical model of tumor-immune surveillance.

    Science.gov (United States)

    Mahasa, Khaphetsi Joseph; Ouifki, Rachid; Eladdadi, Amina; Pillis, Lisette de

    2016-09-01

    We present a novel mathematical model involving various immune cell populations and tumor cell populations. The model describes how tumor cells evolve and survive the brief encounter with the immune system mediated by natural killer (NK) cells and the activated CD8(+) cytotoxic T lymphocytes (CTLs). The model is composed of ordinary differential equations describing the interactions between these important immune lymphocytes and various tumor cell populations. Based on up-to-date knowledge of immune evasion and rational considerations, the model is designed to illustrate how tumors evade both arms of host immunity (i.e. innate and adaptive immunity). The model predicts that (a) an influx of an external source of NK cells might play a crucial role in enhancing NK-cell immune surveillance; (b) the host immune system alone is not fully effective against progression of tumor cells; (c) the development of immunoresistance by tumor cells is inevitable in tumor immune surveillance. Our model also supports the importance of infiltrating NK cells in tumor immune surveillance, which can be enhanced by NK cell-based immunotherapeutic approaches. PMID:27317864

  6. Lymphocyte migration studies in man

    International Nuclear Information System (INIS)

    In this paper the author outlines what is known of the migration and recirculation of the lymphocyte in man and animals. He then attempts to demonstrate how a better grasp of these phenomena may contribute to an understanding of the pathophysiology of human diseases such as chronic lymphocytic leukemia, non-Hodgkin's lymphomas, Hodgkin's, and other diseases

  7. Lymphocyte subsets and response to PHA among atomic bomb survivors

    International Nuclear Information System (INIS)

    In an effort to elucidate the effect of radiation exposure on immune competence in man, the number of lymphocytes, lymphocyte subsets, and the percentage of phytohemagglutinin (PHA)-induced transformation of lymphocytes were determined in 66 cancer patients, 25 of whom were exposed to atomic radiation at ≤ 2,000 m from ground zero and 41 others were not exposed. The number of lymphocytes was decreased with increasing age at exposure. The percentage of OKT3-positive cells tended to be lower in exposed patients who were in their twenties at the time of exposure than the non-exposed patients. Among patients in their teens and twenties at the time of exposure, there was a tendency toward decreased percentage of OKT4-positive cells (T4) and increased percentage of OKT8-positive cells (T8). The T4/T8 ratio was reduced. Patients who were in their first decade of life at the time of exposure tended to have decreased OKIa 1-positive cells, and increased Leulla-positive cells. Patients exposed in their twenties and thirties had slightly decreased percentage of PHA-induced transformation of lymphocytes. (Namekawa, K.)

  8. The Role of the T lymphocytes and Remodeling in Asthma.

    Science.gov (United States)

    Amin, Kawa

    2016-08-01

    In allergic asthma (AA), inflammatory changes in the airway epithelium may contribute to the characteristic pathophysiology and symptoms. The presence of T lymphocytes, eosinophils, mast cells and macrophages, the presence of cytokines, and also structural changes in the airway mucous membrane are characteristic for asthma. Bronchial biopsy specimens were obtained from 33 AA, 25 nonallergic asthma (NAA), and 20 healthy controls (HC). This study used immunohistochemical techniques for identified monoclonal antibodies (CD3, CD4, CD8, CD25, ECP, MBP, tenascin, and laminin) in the bronchi. The highest number of eosinophils and T lymphocyte cells in bronchial biopsies was found in AA, and NAA. The number of T lymphocytes in AA was significantly higher than in NAA and HC. The degree of epithelial damage was higher in the AA group compared to the other groups. The tenascin- and laminin-positive layers in AA were thicker than other groups. In AA, a significant negative correlation was found between epithelial integrity and the count for eosinophils or T lymphocytes. T lymphocytes and eosinophils in AA were found in the area of epithelial and lamina propria damage. This article suggests that T lymphocytes may not only contribute to the chronic airway inflammatory response, airway remodeling, and symptomatology but may also have a central role at the initiation of the allergic immune response. Th-targeted therapy would be of considerable interest in controlling AA. Having more knowledge on the roles of T lymphocytes in the pathogenesis of allergic inflammation highlights the contributions of these cells in regulating and may lead to a new therapeutic target-AA. PMID:27221139

  9. Pet Rodents and Fatal Lymphocytic Choriomeningitis in Transplant Patients

    Centers for Disease Control (CDC) Podcasts

    2007-05-16

    Three organ transplant recipients died from infection with lymphocytic choriomeningitis virus (LCMV), which was traced back to a hamster owned by the daughter of the organ donor. Dr. Brian Amman, a mammalogist with the Special Pathogens Branch at CDC, discusses the dangers LCMV may pose to people with immune disorders, as well as to pregnant women.  Created: 5/16/2007 by CDC, Office of the Director.   Date Released: 5/16/2007.

  10. Different expression patterns of TRP genes in murine B and T lymphocytes

    International Nuclear Information System (INIS)

    A prolonged increase in the intracellular calcium concentration ([Ca2+]i) is essential for lymphocyte activation that includes cell proliferation and differentiation. This increase in [Ca2+]i results from Ca2+ release from the intracellular store and the subsequent Ca2+ influx from the extracellular environment via calcium channels located on the plasma membrane. Although transient receptor potential (TRP) channels have been reported to play important roles in the [Ca2+]i increase in lymphocytes, the function of these channels in lymphocyte activation remains unknown. Here, we report the comprehensive expression profile of TRP channel gene families including TRPC, TRPV, and TRPM in the murine immune system. RT-PCR analysis revealed different expression patterns of the TRP channel genes in B and T lymphocytes isolated from the spleen. Therefore, our results provide an appropriate reference of TRP gene expression in murine lymphocytes

  11. Membrane Surface Nanostructures and Adhesion Property of T Lymphocytes Exploited by AFM

    Directory of Open Access Journals (Sweden)

    Lu Hongsong

    2009-01-01

    Full Text Available Abstract The activation of T lymphocytes plays a very important role in T-cell-mediated immune response. Though there are many related literatures, the changes of membrane surface nanostructures and adhesion property of T lymphocytes at different activation stages have not been reported yet. However, these investigations will help us further understand the biophysical and immunologic function of T lymphocytes in the context of activation. In the present study, the membrane architectures of peripheral blood T lymphocytes were obtained by AFM, and adhesion force of the cell membrane were measured by acquiring force–distance curves. The results indicated that the cell volume increased with the increases of activation time, whereas membrane surface adhesion force decreased, even though the local stiffness for resting and activated cells is similar. The results provided complementary and important data to further understand the variation of biophysical properties of T lymphocytes in the context of in vitro activation.

  12. Similar lymphocytic infiltration pattern in primary breast cancer and their corresponding distant metastases

    OpenAIRE

    Sobottka, Bettina; Pestalozzi, Bernhard; Fink, Daniel; Moch, Holger; Varga, Zsuzsanna

    2016-01-01

    Tumor infiltrating lymphocytes in primary breast cancer (TIL) are acknowledged measures of disease free survival (DFS) in adjuvant and neoadjuvant settings. Little is known about the biology of metastasis infiltrating lymphocytes (mTIL) although the local immunity of the metastatic site may critically influence the infiltrate composite. To address this question we compared mTIL with their matched TIL in 87 breast cancer patients and their corresponding distant metastasis at four different ana...

  13. Endogenous thrombospondin-1 and proteases in the regulation of lymphocyte adhesion and motility

    OpenAIRE

    Forslöw, Anna

    2008-01-01

    The human immune system, which protects the body from invading pathogens, largely depends on the proper function of lymphocytes, which are highly motile and constantly recirculate the blood and lymph. Adhesive and motile capability is often amplified or uncontrolled during chronic inflammatory conditions such as autoimmune diseases. This thesis comprises four studies of T lymphocyte motility and adhesion aiming to elucidate the regulative role of endogenous secretion of enzy...

  14. Evolving Concepts: Immunity in Oncology from Targets to Treatments

    Directory of Open Access Journals (Sweden)

    Hina Khan

    2015-01-01

    Full Text Available Cancer is associated with global immune suppression of the host. Malignancy-induced immune suppressive effect can be circumvented by blocking the immune checkpoint and tip the immune balance in favor of immune stimulation and unleash cytotoxic effects on cancer cells. Human antibodies directed against immune checkpoint proteins: cytotoxic T lymphocytes antigen-4 (CTLA-4 and programmed death-1 (PD-1, programmed death-ligand 1 (PD-L1, have shown therapeutic efficacy in advanced melanoma and non-small-cell lung cancer and other malignancies. Immune check point blockade antibodies lead to diminished tolerance to self and enhanced immune ability to recognize and eliminate cancer cells. As a class these agents have immune-related adverse events due to decreased ability of effector immune cells to discriminate between self and non-self. Seventy percent of patients participating in clinical trials have experienced anticancer activities and varying degrees of immune mediated dose-limiting side effects.

  15. Evolving Concepts: Immunity in Oncology from Targets to Treatments.

    Science.gov (United States)

    Khan, Hina; Gucalp, Rasim; Shapira, Iuliana

    2015-01-01

    Cancer is associated with global immune suppression of the host. Malignancy-induced immune suppressive effect can be circumvented by blocking the immune checkpoint and tip the immune balance in favor of immune stimulation and unleash cytotoxic effects on cancer cells. Human antibodies directed against immune checkpoint proteins: cytotoxic T lymphocytes antigen-4 (CTLA-4) and programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), have shown therapeutic efficacy in advanced melanoma and non-small-cell lung cancer and other malignancies. Immune check point blockade antibodies lead to diminished tolerance to self and enhanced immune ability to recognize and eliminate cancer cells. As a class these agents have immune-related adverse events due to decreased ability of effector immune cells to discriminate between self and non-self. Seventy percent of patients participating in clinical trials have experienced anticancer activities and varying degrees of immune mediated dose-limiting side effects. PMID:26060497

  16. T-lymphocyte subsets in West African children: impact of age, sex, and season

    DEFF Research Database (Denmark)

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

    1997-01-01

    determinants of T-lymphocyte subset levels. METHODS: A total of 803 healthy West African children younger than 6 years were included in the three community studies of T-lymphocyte subsets among twins and singletons, after measles infection and after measles immunization. We used the immunoalkaline phosphatase...... method to determine T-lymphocyte subsets. RESULTS: We found differences by age, sex, and season, whereas there were no significant differences by birth order, twinning, or ethnic group. The CD4+ percentage declined from birth to age 2 years, at which time it started to increase to higher levels at age 4...

  17. The role of stromal mast cells in the modification of CD4 CD25 Foxp3 regulatory T cells, Th17 lymphocytes and cytotoxic lymphocytes Tc1 in the development and progression of tumor

    OpenAIRE

    Katarzyna Starska; Ewa Brzezińska-Błaszczyk

    2010-01-01

    Despite the lack of direct evidence that immune surveillance cells protect against tumor development, indirect clinical observations and experimental studies indicate activity in the immune response against cancer cells of various origin. Little is known about the effects of the stromal tumor mast cell (MC) in the activity of immune cells, i.e. CD4[sup] [/sup]CD25[sup] [/sup]Foxp3[sup] [/sup] regulatory T cells, Th17 lymphocytes, cytotoxic lymphocytes Tc1 and their mutual modulatory function ...

  18. Cellular immune findings in Lyme disease.

    OpenAIRE

    Sigal, L. H.; Moffat, C. M.; Steere, A. C.; Dwyer, J. M.

    1984-01-01

    From 1981 through 1983, we did the first testing of cellular immunity in Lyme disease. Active established Lyme disease was often associated with lymphopenia, less spontaneous suppressor cell activity than normal, and a heightened response of lymphocytes to phytohemagglutinin and Lyme spirochetal antigens. Thus, a major feature of the immune response during active disease seems to be a lessening of suppression, but it is not yet known whether this response plays a role in the pathophysiology o...

  19. Autoimmune Cytopenias in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Giovanni D'Arena

    2013-01-01

    Full Text Available The clinical course of chronic lymphocytic leukemia (CLL may be complicated at any time by autoimmune phenomena.The most common ones are hematologic disorders, such as autoimmune hemolytic anemia (AIHA and immune thrombocytopenia (ITP. Pure red cell aplasia (PRCA and autoimmune agranulocytosis (AG are, indeed, more rarely seen. However, they are probably underestimated due to the possible misleading presence of cytopenias secondary to leukemic bone marrow involvement or to chemotherapy cytotoxicity. The source of autoantibodies is still uncertain, despite the most convincing data are in favor of the involvement of resting normal B-cells. In general, excluding the specific treatment of underlying CLL, the managementof these complications is not different from that of idiopathic autoimmune cytopenias or of those associated to other causes. Among different therapeutic approaches, monoclonal antibody rituximab, given alone or in combination, has shown to be very effective.

  20. Effect of transport stress on peripheral blood lymphocyte subsets and Th cytokines in pigs

    Directory of Open Access Journals (Sweden)

    Wuren Ma

    2013-01-01

    Full Text Available In order to investigate transport stress on porcine peripheral blood lymphocyte subsets and Th cytokines, blood samples were collected from pigs before and after transport. Creatine kinase (CK, alkaline phosphatase (ALP, lactate dehydrogenase (LDH, glucose, and cortisol in the serum were measured. The number of leukocytes and lymphocytes, percentages of lymphocyte subsets, as well as Th cell cytokines level and their mRNA expression were detected, respectively. After transport, the level of CK, glucose and interleukin (IL-4 increased significantly (p<0.01, LDH, Th memory cells, natural killer and interferon (IFN-γ increased significantly (p<0.05, cortisol, number of leukocytes and lymphocytes decreased (p<0.01, percentages of γ δ T cells, naïve Th cells and cytotoxic T lymphocytes decreased significantly (p<0.05. The mRNA expressions IL-2 and IFN-γ were down regulated, p<0.01 and p<0.05, respectively. While IL-4, IL-6, and IL-10 were up regulated, but only IL-10 displayed a highly significant difference (p<0.01. These data suggested that transport could cause immune suppression in pigs, which influences cellular immunity more than humoral immunity, and humoral immunity may play an important role in transport stress. Proper measures should be taken to reduce susceptibility of infection after transport.

  1. Immune recovery vitritis

    Directory of Open Access Journals (Sweden)

    Dujić Mirjana

    2007-01-01

    Full Text Available Introduction Immune recovery vitritis (IRV is symptomatic vitritis of > 1+ severity associated with inactive cytomegalovirus (CMV retinitis. It is an opportunistic infection of the eye, in the patients who suffer from AIDS, and is treated with a highly active antiretroviral therapy (HAART. As a result of this therapy, there is an immune reconstitution in the body and inflammation of the vitreous body. Objective The aim of the study was to show the incidence of IRV in patients treated with HAART. Method A retrospective study was conducted in patients who suffered from CMV retinitis. Twenty-one were treated with HAART and had the diagnosis of CMV retinitis, as well. All of them were examined by the same ophthalmologist who peformed slit lamp examination with mydriasis and indirect ophthalmoscopy. Results Nine of 21 patients developed IRV as a complication of HAART, two had cystoid macular edema (CMO. Conclusion CMV retinitis develops when the number of CD4+ T lymphocytes drops below 50/mm3. This results in necrotic retinitis which, if untreated, leads to complete loss of vision. With the introduction of HAART, we learned that the reconstitution of immune status was achieved as well as life expectancy, but there was a dramatic decline in the opportunistic infection, including CMV retinitis, as well. With the immune reconstitution, the inflammation develops in the eye, known as IRV. Sometimes, it is necessary to treat this condition, but in the case of our patients, the inflammation was mild, and no treatment was necessary.

  2. Radiosensitivity of lymphocytes in vitro

    International Nuclear Information System (INIS)

    The radiation-induced impairment of human T-lymphocytes was studied after in vitro exposure to 25.8 - 825.6 mC/kg (100 - 3200 R) of 60Co γ-radiation by ascertaining the change in lymphocyte response to phytohaemagglutin stimulation. Following methods were used: (1) measurement of 3H-thymidine uptake, (2) E-rosette test, and (3) morphological examination of transformed T-cells. The results revealed a dose-dependent decline in T-cell number which was still somewhat more marked with lymphocytes purified over Ficoll-Isopaque prior to irradiation. (author)

  3. Flow-cytometric analysis of changes of OKT6+-lymphocytes in the blood of cancer patients during radiation therapy

    International Nuclear Information System (INIS)

    In this study, we report a clinical application of a rapid flow-cytometric immuno-fluorescence method for studying OKT6+-lymphocytes in whole blood by using monoclonal antibody OKT6. Changes in the relative percentages and absolute counts of OKT6+-lymphocytes during radiotherapy of cancer patients were evaluated by this method. In a study of 112 samples from 47 cases, the elevation of OKT6+-lymphocyte level was observed in 10 samples from 9 patients with primary lung cancer or uterine cancer. About 18 cases with lung cancer, the elevation of OKT6+-lymphocyte level was observed in 7 patients. And 5 of these 7 patients did not so respond to radiation therapy. In contrast, the continuous low level of OKT6+-lymphocyte was observed in patients with good response. OKT6+-lymphocyte level could be a valuable parameter for evaluating alterations of immune responses in cancer patients during radiotherapy. (author)

  4. A thermodynamic perspective of immune performances

    CERN Document Server

    Agliari, Elena; Guerra, Francesco; Moauro, Francesco

    2011-01-01

    We consider the mutual interactions, via cytokine exchanges, among helper lymphocytes, B lymphocytes and killer lymphocytes, and we model them as a unique system by means of a tripartite network. Each party includes all the different clones of the same lymphatic subpopulation, whose couplings to the others are either excitatory or inhibitory (mirroring elicitation and suppression by cytokine): First of all, we show that this system can be mapped into an associative neural network, where helper cells directly interact with each other and are able to secrete cytokines according to "strategies" learnt by the system and profitable to cope with possible antigenic stimulation; the ability of such a retrieval corresponds to an healthy reaction of the immune system. We then investigate the possible conditions for the failure of a correct retrieval and distinguish between the following outcomes: massive lymphocyte expansion/suppression (e.g. lymphoproliferative syndromes), subpopulation unbalance (e.g. HIV, EBV infect...

  5. Skin Immunization Obviates Alcohol-Related Immune Dysfunction

    Directory of Open Access Journals (Sweden)

    Rhonda M. Brand

    2015-11-01

    Full Text Available Alcoholics suffer from immune dysfunction that can impede vaccine efficacy. If ethanol (EtOH-induced immune impairment is in part a result of direct exposure of immune cells to EtOH, then reduced levels of exposure could result in less immune dysfunction. As alcohol ingestion results in lower alcohol levels in skin than blood, we hypothesized that the skin immune network may be relatively preserved, enabling skin-targeted immunizations to obviate the immune inhibitory effects of alcohol consumption on conventional vaccines. We employed the two most common chronic EtOH mouse feeding models, the liver-damaging Lieber-DeCarli (LD and liver-sparing Meadows-Cook (MC diets, to examine the roles of EtOH and/or EtOH-induced liver dysfunction on alcohol related immunosuppression. Pair-fed mice were immunized against the model antigen ovalbumin (OVA by DNA immunization or against flu by administering the protein-based influenza vaccine either systemically (IV, IM, directly to liver (hydrodynamic, or cutaneously (biolistic, ID. We measured resulting tissue EtOH levels, liver stress, regulatory T cell (Treg, and myeloid-derived suppressor cell (MDSC populations. We compared immune responsiveness by measuring delayed-type hypersensitivity (DTH, antigen-specific cytotoxic T lymphocyte (CTL, and antibody induction as a function of delivery route and feeding model. We found that, as expected, and independent of the feeding model, EtOH ingestion inhibits DTH, CTL lysis, and antigen-specific total IgG induced by traditional systemic vaccines. On the other hand, skin-targeted vaccines were equally immunogenic in alcohol-exposed and non-exposed subjects, suggesting that cutaneous immunization may result in more efficacious vaccination in alcohol-ingesting subjects.

  6. Levels of immune cells in transcendental meditation practitioners

    Directory of Open Access Journals (Sweden)

    Jose R Infante

    2014-01-01

    Conclusions: The technique of meditation studied seems to have a significant effect on immune cells, manifesting in the different circulating levels of lymphocyte subsets analyzed. The significant effect of TM on the neuroendocrine axis and its relationship with the immune system may partly explain our results.

  7. T cells and the humoral immune system

    NARCIS (Netherlands)

    W.B. van Muiswinkel (Willem)

    1975-01-01

    textabstractLymphoid cells and macrophages play an important role in the development and rnaintance of humoral and cellular immunity in mammals. The lymphoid cells in the peripheral lymphoid organs are divided into two major classes: (1) thymus-derived lymphocytes or T cells and (2) bursa-equivalent

  8. Analysis of IL-2-like factor in lymphocyte culture supernatant of olive flounder, Paralichthys oliveaceus

    Institute of Scientific and Technical Information of China (English)

    WU Riqin; ZHANG Peijun; LI Jun; XU Yongli

    2005-01-01

    To study immune mechanism of fish lymphocyte we performed a proliferation assay and ELISA using monoclonal antibody against human IL-2. The result showed that an interleukin-2 (IL-2)-like factor was detected in the supernatant of plant haemoglutinin (PHA)-stimulated lymphocyte culture from peripheral blood,spleen and head kidney of olive flounder, Paralichthys olivaceus. The quantities of IL-2-1ike factor in the supematant from different lymphoid tissues were quite different. The IL-2 like factor in the supernatant from cultured head kidney lymphocytes was much higher than those of peripheral blood lymphocytes and spleen lymphocytes (P<0.01). The IL-2 activity was found in either mouse thymocyte proliferation assay or flounder head kidney lymphocyte proliferation assay and shown to have obvious enhancing effect on proliferation of the above two types of cell. The recombinant human IL-2 (rhIL-2) was able to stimulate flounder thymocyte proliferation and used to detect the IL-2 receptor (IL-2R) on the surface of flounder lymphocyte. The cross-reaction between the lymphocytes of flounder peripheral blood and CD25(IL-2R) was detected with flow cytometry and shown that the percentage of CD25-positive cell in peripheral blood was 7.74± 0.67%.

  9. The role of regulatory T cells in the modulation of anti-tumor immune response

    OpenAIRE

    Radosavljević Gordana D.; Jovanović Ivan P.; Kanjevac Tatjana V.; Arsenijević Nebojša N.

    2013-01-01

    It has been shown that the loss of regulatory function by deple­ + Regulatory T cells (Treg) represent a subset of CD4 T cells whose function is to suppress immune responses. Treg lymphocytes can be divided into two subsets: natural nTreg lymphocytes that are developed in the thymus and inducible iTreg lymphocytes, which originate from conventional T lymphocytes on the periphery. The majority of Treg lymphocytes express high levels of interleukin­2 (IL­2) receptor α chain (CD25) and tra...

  10. Gamma-delta T lymphocytes coordinate eosinophil influx during allergic responses

    Directory of Open Access Journals (Sweden)

    Maria Das GraçasMuller De OliveiraHenriques

    2012-12-01

    Full Text Available Tissue eosinophil infiltration, which is a hallmark of allergic and helminthic diseases, is mainly coordinated by T lymphocytes, via the production of eosinophilotactic chemokines. Among T lymphocyte subsets, lymphocytes expressing gamma delta TCR have been determined as a key factor for eosinophil accumulation via direct and indirect mechanisms. This knowledge is strongly supported by the fact that, in different experimental models of eosinophilic airway inflammation and helminth-induced Th2 lung inflammation, an evident tissue accumulation of gamma delta T lymphocytes is observed. In addition, the depletion of gamma delta T lymphocytes is correlated with the impairment of eosinophil accumulation in inflamed tissue. Gamma delta T lymphocytes are non-conventional T lymphocytes, which comprise a minor T lymphocyte subset, mainly distributed in the tissue, and present crucial roles in innate and acquired immune responses. Gamma delta T lymphocytes recognize several danger- and pathogen-associated molecular pattern molecules and stress antigens in a MHC-independent fashion and can provide rapid tissue-specific responses, via the production of a wide range of chemical mediators capable to modulate other cell populations. These mediators include chemoattractant cytokines and chemokines that attract eosinophils into the tissue by either direct recognition (such as IL-5, CCL11/eotaxin, or indirect mechanisms via the modulation of alpha beta T lymphocytes and macrophages (through the production of interferon-γ, IL-4 and CCL2/MCP-1, for example. The present review presents an overview of how gamma delta T lymphocytes coordinate eosinophil accumulation in allergy, by focusing on their role in airway inflammation and by discussing the involvement of cytokines and chemokines in this phenomenon.

  11. Lymphocyte protein synthesis is increased with the progression of HIV-associated disease to AIDS.

    Science.gov (United States)

    Caso, G; Garlick, P J; Gelato, M C; McNurlan, M A

    2001-12-01

    HIV infection has been shown to affect lymphocyte function and to reduce lymphocyte responsiveness in vitro to mitogenic stimulation, but little is known about lymphocyte metabolism in vivo and how it is affected during the course of the disease. This study investigated the metabolic activity of lymphocytes in vivo through the progression of HIV-associated disease. Lymphocyte protein synthesis was measured with L-[(2)H(5)]phenylalanine (45 mg/kg body weight) in healthy volunteers (n=7), in patients who were HIV-positive (n=7) but asymptomatic, and in patients with AIDS (n=8). The rates of lymphocyte protein synthesis [expressed as a percentage of lymphocyte protein, i.e. fractional synthesis rate (FSR)] were not altered in HIV-positive patients compared with healthy controls (7.9+/-1.28% and 9.1+/-0.53%/day respectively), but were significantly elevated in AIDS patients (14.0+/-1.16%/day; P<0.05). The serum concentration of the cytokine tumour necrosis factor-alpha (TNF-alpha) increased with the progression of the disease, and TNF-alpha levels were significantly higher in AIDS patients (6.81+/-0.88 ng/l) than in healthy controls (3.09+/-0.27 ng/l; P<0.05). Lymphocyte protein FSR was positively correlated with serum TNF-alpha concentration (r=0.55, P=0.009) and negatively correlated with CD4(+) lymphocyte count (r=-0.70, P=0.004). The elevation of lymphocyte protein synthesis in AIDS patients suggests a higher rate of turnover of lymphocytes. This may be associated with a generalized activation of the immune system, which is also reflected by the elevated serum TNF-alpha concentration in the late stages of HIV-associated disease. PMID:11724643

  12. T-lymphocyte subsets in HIV-infected and high-risk HIV-uninfected adolescents - Retention of naive T lymphocytes in HIV-infected adolescents

    NARCIS (Netherlands)

    Douglas, SD; Rudy, B; Muenz, L; Starr, SE; Campbell, DE; Wilson, C; Holland, C; Crowley-Nowick, P; Vermund, SH

    2000-01-01

    Background: The capacity of the immune system of adolescents to generate and repopulate naive and memory cell populations under conditions of normal homeostasis and human immunodeficiency virus (HIV) infection is largely unknown. Objective: To assess lymphocyte subsets in HIV-infected and high-risk

  13. What Is Chronic Lymphocytic Leukemia?

    Science.gov (United States)

    ... Topic Normal bone marrow, blood, and lymphoid tissue What is chronic lymphocytic leukemia? Cancer starts when cells ... body, including the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts ...

  14. Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

    International Nuclear Information System (INIS)

    Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH)2D3, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion

  15. Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

    Energy Technology Data Exchange (ETDEWEB)

    Whelan, Jarrett T.; Wang, Lei; Chen, Jianming; Metts, Meagan E.; Nasser, Taj A.; McGoldrick, Liam J. [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); Bridges, Lance C., E-mail: bridgesl@ecu.edu [Department of Biochemistry and Molecular Biology, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States); East Carolina Diabetes and Obesity Institute, The Brody School of Medicine at East Carolina University, Greenville, NC 27834 (United States)

    2014-11-28

    Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid X receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH){sub 2}D{sub 3}, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion.

  16. Long term lymphocyte reconstitution after alemtuzumab treatment of multiple sclerosis

    KAUST Repository

    Hill-Cawthorne, Grant A.

    2011-11-05

    Background: Alemtuzumab is a lymphocyte depleting monoclonal antibody that has demonstrated superior efficacy over interferon β-1a for relapsing-remitting multiple sclerosis (MS), and is currently under investigation in phase 3 trials. One unresolved issue is the duration and significance of the lymphopenia induced. The long term effects on lymphocyte reconstitution of a single course, and the consequences that this has on disability, morbidity, mortality and autoimmunity, were examined. Methods: The lymphocyte reconstitution (n=36; 384 person years) and crude safety data (n=37; 447 person years) are reported for the first patients with progressive MS to receive alemtuzumab (1991-1997). Reconstitution time was expressed as a geometric mean or, when a non-negligible number of individuals failed to recover, as a median using survival analysis. Results: Geometric mean recovery time (GMRT) of total lymphocyte counts to the lower limit of the normal range (LLN; ≥1.0×10 9 cells/l) was 12.7 months (95% CI 8.8 to 18.2 months). For B cells, GMRT to LLN (≥0.1×10 9/l) was 7.1 months (95% CI 5.3 to 9.5); median recovery times for CD8 (LLN ≥0.2×10 9 cells/l) and CD4 lymphocytes (LLN ≥0.4×10 9 cells/l) were 20 months and 35 months, respectively. However, CD8 and CD4 counts recovered to baseline levels in only 30% and 21% of patients, respectively. No infective safety concerns arose during 447 person years of follow-up. Conclusions: Lymphocyte counts recovered to LLN after a single course of alemtuzumab in approximately 8 months (B cells) and 3 years (T cell subsets), but usually did not recover to baseline values. However, this long lasting lymphopenia in patients with a previously normal immune system was not associated with an increased risk of serious opportunistic infection.

  17. In Vitro Influence of Mycophenolic Acid on Selected Parameters of Stimulated Peripheral Canine Lymphocytes

    Science.gov (United States)

    Guzera, Maciej; Szulc-Dąbrowska, Lidia; Cywińska, Anna; Archer, Joy; Winnicka, Anna

    2016-01-01

    Mycophenolic acid (MPA) is an active metabolite of mycophenolate mofetil, a new immunosuppressive drug effective in the treatment of canine autoimmune diseases. The impact of MPA on immunity is ambiguous and its influence on the canine immune system is unknown. The aim of the study was to determine markers of changes in stimulated peripheral canine lymphocytes after treatment with MPA in vitro. Twenty nine healthy dogs were studied. Phenotypic and functional analysis of lymphocytes was performed on peripheral blood mononuclear cells cultured with mitogens and different MPA concentrations– 1 μM (10−3 mol/m3), 10 μM or 100 μM. Apoptotic cells were detected by Annexin V and 7-aminoactinomycin D (7-AAD). The expression of antigens (CD3, CD4, CD8, CD21, CD25, forkhead box P3 [FoxP3] and proliferating cell nuclear antigen [PCNA]) was assessed with monoclonal antibodies. The proliferation indices were analyzed in carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled cells. All analyses were performed using flow cytometry. The influence of MPA on apoptosis was dependent on the mechanism of cell activation and MPA concentration. MPA caused a decrease in the expression of lymphocyte surface antigens, CD3, CD8 and CD25. Its impact on the expression of CD4 and CD21 was negligible. Its negative influence on the expression of FoxP3 was dependent on cell stimulation. MPA inhibited lymphocyte proliferation. In conclusion, MPA inhibited the activity of stimulated canine lymphocytes by blocking lymphocyte activation and proliferation. The influence of MPA on the development of immune tolerance–expansion of Treg cells and lymphocyte apoptosis–was ambiguous and was dependent on the mechanism of cellular activation. The concentration that MPA reaches in the blood may lead to inhibition of the functions of the canine immune system. The applied panel of markers can be used for evaluation of the effects of immunosuppressive compounds in the dog. PMID:27138877

  18. [Chronic lymphocytic leukemia].

    Science.gov (United States)

    Aoki, Sadao

    2016-03-01

    Currently, several novel drugs are available for chronic lymphocytic leukemia (CLL) in Western countries. Of these drugs, those that inhibit the B-cell receptor (BCR) signaling pathway are the most promising. Ibrutinib inhibits BTK in the BCR pathway and can be administered orally. The results of several clinical trials suggest that ibrutinib is highly effective against relapsed/resistant (RR) and treatment-naïve CLL. Furthermore, ibrutinib shows equivalent efficacy on CLL with the 17p deletion. Idelalisib, which also blocks the BCR pathway, inhibits PIK3delta and induces CLL cell death. Clinical trials have shown outstanding efficacy of idelalisib against RR-CLL, especially when administered with antiCD20 antibodies. This drug is also effective against CLL with the 17p deletion. ABT-199 is another novel drug; it inhibits BCL2 signaling, not the BCR pathway, and can be administered orally. The efficacy of ABT-199 against RR-CLL has been demonstrated in a number of clinical trials. These drugs have only mild toxicity and can be used for patients in poor general condition. Unfortunately, none of these drugs have yet been approved in Japan. Rapid resolution of the 'drug lag' problem is necessary. PMID:27076234

  19. Growth hormone-insulinlike growth factor I and immune function.

    Science.gov (United States)

    Gelato, M C

    1993-04-01

    Growth hormone (GH) and insulinlike growth factor I (IGF-I) may be part of a neuroendocrine immune axis that stimulates cellular proliferation of primary lymphoid organs (bone marrow, thymus) as well as stimulates activation of peripheral lymphocytes and macrophages to enhance specific immune responses. GH can also stimulate production of thymic hormones and cytokines, and in this way impact on immune function. It is not clear whether GH and IGF-I act independently or whether the action of GH is mediated by local production of IGF-I by lymphocytes. Both GH and IGF-I and their receptors are present in lymphocytes. Thus, cells of the immune system may be important targets of the GH-IGF-I axis. PMID:18407143

  20. Analysis of the T-Lymphocytes and Their Subpopu-lations of the Peripheral Blood in Patients with Urticaria

    Institute of Scientific and Technical Information of China (English)

    王冬云; 彭振辉; 谭升顺; 楚瑞琦; 刘平

    2003-01-01

    Objective: To study the function of cellular immunity of patients with urticaria.Methods:T-lymphocytes subpopulations of the peripheraal blood in 60 patients with urticaria and 40 henlthy controls were examined by flow cylonuetry. Results: The number of CD3+ and CD4+ cells in the urticaria group were significantly lower than those in the control group ( P<0. 01 ), especially in patients with acute urticaria. Conclusion: There was immunologic dysfunction of T lymphocyte in the patients with urticaria, and not only humoral immunity takes part but also cellular immunity plays a certain role in the pathogenesis of urticaria.

  1. The study on the induction of specific immune cytotoxic T lymphocyte responses against pancreatic cancer by transfected dendritic cells with common tumor antigen survivin mRNAs in vitro%Survivin mRNA转染树突细胞诱导特异性抗胰腺癌免疫反应的体外研究

    Institute of Scientific and Technical Information of China (English)

    郭晓钟; 陈江

    2011-01-01

    Objective To investigate the induction of specific anti-tumor immune response by transfected dendritic cells (DCs) with survivin mRNA of human pancreatic cancer, and to provide the experimental evidences for the treatment of human pancreatic cancer with DCs vaccine. Methods DCs were isolated and cultured from peripheral blood mononuclear cells (PBMCs). After being transcripted and amplified, survivin mRNA was transfected into DCs by electroporation. The expression of survivin in DCs at different time points was detected by quantitative real-time PCR. The survival rate of DCs before and after transfection was determined by MTT method. The induction of specific cytotoxic T lymphocyte (CTL) response by survivin mRNA transfected DCs was measured by 51Cr standard cytotoxicity test. The induction of specific CTL activation by survivin mRNA transfected DCs was evaluated through testing released IFN-γ by ELISA method. Results After survivin mRNA transfection for 48h, the expression of survivin mRNA in DCs reached the highest point (46.09±6.57). After transfection, the survival rate of DCs was stabilized around 80%. The DCs transfected with survivin mRNA could effectively induce HLA-A2+ / survivin+ specific CTL immune responses. Stimulated with pancreatic cancer cell line Capan-2 cells or SCL-1 cells as control group, the IFN-γ released in 24 hours by survivin specific CTL were (28.79±5.70) U/ml and (25.12±2.13) U/ml respectively, there was no significant difference (P=0.761). Conclusion The induction of CTLs by DCs transfected with human pancreatic cancer survivin mRNA could produce specific anti-tumor immunity.%目的 研究人胰腺癌survivin mRNA转染树突细胞(DC)诱导的特异性抗肿瘤免疫反应,为DC疫苗治疗胰腺癌提供实验依据.方法 自样本外周血单核细胞中分离和培养DC.体外转录和PCR扩增survivin mRNA后使用电穿孔法将其转染DC.采用实时定量PCR技术检测不同时间点DC中survivin的表达.用四甲基

  2. Immunity to bacterial infection in the chicken.

    Science.gov (United States)

    Wigley, Paul

    2013-11-01

    Bacterial infections remain important to the poultry industry both in terms of animal and public health, the latter due to the importance of poultry as a source of foodborne bacterial zoonoses such as Salmonella and Campylobacter. As such, much focus of research to the immune response to bacterial infection has been to Salmonella. In this review we will focus on how research on avian salmonellosis has developed our understanding of immunity to bacteria in the chicken from understanding the role of TLRs in recognition of bacterial pathogens, through the role of heterophils, macrophages and γδ lymphocytes in innate immunity and activation of adaptive responses to the role of cellular and humoral immunity in immune clearance and protection. What is known of the immune response to other bacterial infections and in particular infections that have emerged recently as major problems in poultry production including Campylobacter jejuni, Avian Pathogenic Escherichia coli, Ornithobacterium rhinotracheale and Clostridium perfringens are discussed. PMID:23648643

  3. Verification of immune response optimality through cybernetic modeling.

    Science.gov (United States)

    Batt, B C; Kompala, D S

    1990-02-01

    An immune response cascade that is T cell independent begins with the stimulation of virgin lymphocytes by antigen to differentiate into large lymphocytes. These immune cells can either replicate themselves or differentiate into plasma cells or memory cells. Plasma cells produce antibody at a specific rate up to two orders of magnitude greater than large lymphocytes. However, plasma cells have short life-spans and cannot replicate. Memory cells produce only surface antibody, but in the event of a subsequent infection by the same antigen, memory cells revert rapidly to large lymphocytes. Immunologic memory is maintained throughout the organism's lifetime. Many immunologists believe that the optimal response strategy calls for large lymphocytes to replicate first, then differentiate into plasma cells and when the antigen has been nearly eliminated, they form memory cells. A mathematical model incorporating the concept of cybernetics has been developed to study the optimality of the immune response. Derived from the matching law of microeconomics, cybernetic variables control the allocation of large lymphocytes to maximize the instantaneous antibody production rate at any time during the response in order to most efficiently inactivate the antigen. A mouse is selected as the model organism and bacteria as the replicating antigen. In addition to verifying the optimal switching strategy, results showing how the immune response is affected by antigen growth rate, initial antigen concentration, and the number of antibodies required to eliminate an antigen are included. PMID:2338827

  4. Investigation of the effects of lymphocyte sub-groups of the use of Maraş powder (Nicotiana rustica L.

    Directory of Open Access Journals (Sweden)

    Nuriye İsmihan Ece Paköz

    2013-03-01

    Full Text Available Objective: This study was to investigate theeffects of lymphocyte sub-groups of the use ofMaraş powder.Method: This study used healthy volunteers,and no smoking or Maras powder (control groupused healthy volunteers. The blood samples forlymphocyte subsets of the cellular immune systemlymphocyte subsets of antibodies were evaluatedwith Becton Dickinson kits using a flow-cytometrikmethod.Results: Case group averages of CD4+/CD8+ Tcell ratios, CD19+ (B lymphocytes and the meanpercentage of CD4+ T lymphocytes were significantlylower than the control group (p0.05.Conclusions: Maras powder increases thecellular immunity relative in the smoking addictivepeople, while humoral immunity declines.As a result, immune responses that is resultingwith any deviation, predisposing factor for avariety of diseases. Therefore, informing of themaras powder users should be considered for harming their health as smoking as well.

  5. Stimulation of lymphocyte anti-melanoma activity by co-cultured macrophages activated by complex homeopathic medication

    International Nuclear Information System (INIS)

    Melanoma is the most aggressive form of skin cancer, and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have been uniformly disappointing. A Brazilian complex homeopathic medication (CHM), used as an immune modulator, has been recommended for patients with depressed immune systems. Previous studies in mice have demonstrated that the CHM activates macrophages, induces an increase in the number of leukocytes and improves the murine response against Sarcoma-180. Here we studied the interaction of mouse lymph node lymphocytes, co-cultured in vitro with macrophages in the presence or absence of the CHM, with B16F10 melanoma cells. Lymphocytes co-cultured with macrophages in the presence of the CHM had greater anti-melanoma activity, reducing melanoma cell density and increasing the number of lysed tumor cells. There was also a higher proportion of activated (CD25+) lymphocytes with increased viability. Overall, lymphocytes activated by treatment destroyed growing cancer cells more effectively than control lymphocytes. Co-culture of macrophages with lymphocytes in the presence of the CHM enhanced the anti-cancer performance of lymphocytes against a very aggressive lineage of melanoma cells. These results suggest that non-toxic therapies using CHMs are a promising alternative approach to the treatment of melanomas. In addition, they are attractive combination-therapy candidates, which may enhance the efficacy of conventional medicines by improving the immune response against tumor cells

  6. The cross-talk between enterocytes and intraepithelial lymphocytes.

    Science.gov (United States)

    Vitale, Serena; Picascia, Stefania; Gianfrani, Carmen

    2016-12-01

    The gut mucosa is continuously exposed to food and microbial antigens. Both enterocytes and intraepithelial lymphocytes have a pivotal role in maintaining the integrity of intestinal mucosa, as these cells guarantee a first line of defense against pathogens and toxic molecules. Enterocytes maintain a physical barrier against microbes and directly contribute to the gut homeostasis by sampling the luminal agents through several pattern recognition receptors or presenting antigen to mucosa T cells. Similarly, due to a close physical contact with the intestinal epithelial cells, the intraepithelial lymphocytes represent an important part of the gut lymphoid tissue, contrasting the entry and spread of pathogens. An alteration of the cross-talk between intestinal epithelial cells and intraepithelial lymphocytes might actively contribute to the development of intestinal immune disorders, as occurring in patients with celiac disease. In genetically predisposed individuals, the gluten exposure results in a massive production of interleukin-15, activation of intraepithelial lymphocytes, and modification of small intestinal mucosa architecture and function. We will review the recent studies on the pathophysiology of cross-talk between enterocytes and intraepithelial T cells, and how this interaction is crucial for intestinal integrity and homeostasis. PMID:27251606

  7. Regulatory T-lymphocytes in asthma.

    Science.gov (United States)

    van Oosterhout, A J M; Bloksma, N

    2005-11-01

    T-helper cell type (Th)2 lymphocytes play an important role in the initiation, progression and persistence of allergic diseases, including asthma. However, little is known about immunoregulatory mechanisms that determine susceptibility to, severity of, or persistence of asthma. The concept of a disturbed Th1/Th2 balance, although having furthered the present understanding of immunoregulation in asthma, has recently been named a "procrustean paradigm", because of its failure to adequately explain many (pre)clinical observations. In recent years, the general knowledge regarding the regulation of infectious, autoimmune diseases, asthma and allergen immunotherapy by T-regulatory (Treg) cells, has rapidly increased. Many different Treg subsets have been described, including CD8+ Treg cells, natural killer (NK) cells and several different CD4+ Treg cell subsets. In this review, the authors will focus on two major and well-described CD4+ Treg cell subsets. These consist of naturally occurring CD25+ Treg cells and adaptive Treg cells that are postulated to prevent immune responses against self-antigens and adaptive immune responses, respectively. The adaptive T-regulatory cells are further subdivided into T-regulatory cells type 1 and T-helper cell type 3 that mediate suppression exclusively via the cytokines interleukin-10 and transforming growth factor-beta, respectively. PMID:16264056

  8. Apicobasal Polarity Controls Lymphocyte Adhesion to Hepatic Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Natalia Reglero-Real

    2014-09-01

    Full Text Available Loss of apicobasal polarity is a hallmark of epithelial pathologies. Leukocyte infiltration and crosstalk with dysfunctional epithelial barriers are crucial for the inflammatory response. Here, we show that apicobasal architecture regulates the adhesion between hepatic epithelial cells and lymphocytes. Polarized hepatocytes and epithelium from bile ducts segregate the intercellular adhesion molecule 1 (ICAM-1 adhesion receptor onto their apical, microvilli-rich membranes, which are less accessible by circulating immune cells. Upon cell depolarization, hepatic ICAM-1 becomes exposed and increases lymphocyte binding. Polarized hepatic cells prevent ICAM-1 exposure to lymphocytes by redirecting basolateral ICAM-1 to apical domains. Loss of ICAM-1 polarity occurs in human inflammatory liver diseases and can be induced by the inflammatory cytokine tumor necrosis factor alpha (TNF-α. We propose that adhesion receptor polarization is a parenchymal immune checkpoint that allows functional epithelium to hamper leukocyte binding. This contributes to the haptotactic guidance of leukocytes toward neighboring damaged or chronically inflamed epithelial cells that expose their adhesion machinery.

  9. Hodgkin Disease and the Role of the Immune System

    OpenAIRE

    Kennedy-Nasser, Alana A.; Hanley, Patrick; Bollard, Catherine M.

    2011-01-01

    Hodgkin disease (HD) is a malignancy of primarily B lymphocytes, which has the unique ability to cause immunodeficiency, as well as provide immune evasion mechanisms to avoid self-destruction. In this review, we will discuss Hodgkin disease, its association with EBV, the immune deficiency caused by HD, tumor immune evasion mechanisms. Specifically, we will closely evaluate the roles of regulatory T cells in HD, cytotoxic T cells, cytokine and chemokine secretion, downregulation of Fas ligand ...

  10. Regulation of the adaptive immune system by innate lymphoid cells

    OpenAIRE

    Hepworth, Matthew R.; Sonnenberg, Gregory F.

    2014-01-01

    Innate lymphoid cells (ILCs) are a group of lymphocytes that promote rapid cytokine-dependent innate immunity, inflammation and tissue repair. In addition, a growing body of evidence suggests ILCs can influence adaptive immune cell responses. During fetal development a subset of ILCs orchestrate the generation and maturation of secondary lymphoid tissues. Following birth, ILCs continue to modulate adaptive immune cell responses indirectly through interactions with stromal cells in lymphoid ti...

  11. Ex vivo cytosolic delivery of functional macromolecules to immune cells.

    Directory of Open Access Journals (Sweden)

    Armon Sharei

    Full Text Available Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.

  12. The Importance of the Nurse Cells and Regulatory Cells in the Control of T Lymphocyte Responses

    Directory of Open Access Journals (Sweden)

    María Guadalupe Reyes García

    2013-01-01

    Full Text Available T lymphocytes from the immune system are bone marrow-derived cells whose development and activities are carefully supervised by two sets of accessory cells. In the thymus, the immature young T lymphocytes are engulfed by epithelial “nurse cells” and retained in vacuoles, where most of them (95% are negatively selected and removed when they have an incomplete development or express high affinity autoreactive receptors. The mature T lymphocytes that survive to this selection process leave the thymus and are controlled in the periphery by another subpopulation of accessory cells called “regulatory cells,” which reduce any excessive immune response and the risk of collateral injuries to healthy tissues. By different times and procedures, nurse cells and regulatory cells control both the development and the functions of T lymphocyte subpopulations. Disorders in the T lymphocytes development and migration have been observed in some parasitic diseases, which disrupt the thymic microenvironment of nurse cells. In other cases, parasites stimulate rather than depress the functions of regulatory T cells decreasing T-mediated host damages. This paper is a short review regarding some features of these accessory cells and their main interactions with T immature and mature lymphocytes. The modulatory role that neurotransmitters and hormones play in these interactions is also revised.

  13. [Ocular immune reconstitution inflammatory syndrome].

    Science.gov (United States)

    Ma, N; Ye, J J

    2016-02-11

    Immune reconstitution inflammatory syndrome (IRIS) is a collection of inflammatory disorders associated with paradoxical worsening of preexisting infectious processes or emerging diseases or even dead after the initiation of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV) infected individuals in a period of recovery of immune function. Ocular immune reconstitution inflammatory syndrome is mainly caused by cytomegalovirus which performing a series of ocular inflammation accompanied with the increase of CD4+ T lymphocytes, such as cytomegalovirus retinitis, after HAART. With HAART widely used, the patients of IRIS gradually increased. But the clinical presentations of IRIS were various because of different pathogens. This review summarized the clinical manifestations, risk factors, diagnosis and treatment of ocular IRIS.(Chin J Ophthalmol, 2016, 51: 150-153). PMID:26906710

  14. Immune tolerance in radiation chimeras

    International Nuclear Information System (INIS)

    Establishment of immune tolerance in radiation chimeras and the mechanism of maintaining it were discussed from certain points. Semiallogeneic radiation chimeras are mostly of long-living, and the hematopoietic organ of this individual consists mainly of the cells derived from the marrow donor, i. e., F1-type cells. F1-type lymphocytes can distinguish parental strain cells from themselves. In these chimeras, a F1-skin graft maintains to be fresh as long as the host is alive, showing immune tolerance effective through its life. In establishment and maintenance of this immune tolerance, the suppressing mechanism of host-type or F1-type seems to be involved. The allogeneic radiation chimera has very poor long-survival rate compared with that of the semiallogeneic radiation chimera. To raise this survival rate, efforts are now being made from the immunological point of view. (Ueda, J.)

  15. Characterization of Cytotoxic T Lymphocyte Function After Foot-and-Mouth Disease Virus Infection and Vaccination

    OpenAIRE

    Patch, Jared R; Kenney, Mary; Pacheco, Juan M.; Grubman, Marvin J.; Golde, William T.

    2013-01-01

    The induction of neutralizing antibodies specific for foot-and-mouth disease virus (FMDV) has been the central goal of vaccination efforts against this economically important disease of cloven-hoofed animals. Although these efforts have yielded much success, challenges remain, including little cross-serotype protection and inadequate duration of immunity. Commonly, viral infections are characterized by induction of cytotoxic T lymphocytes (CTL), yet the function of CTL in FMDV immunity is poo...

  16. Echinoderm immunity.

    Science.gov (United States)

    Smith, L Courtney; Ghosh, Julie; Buckley, Katherine M; Clow, Lori A; Dheilly, Nolwenn M; Haug, Tor; Henson, John H; Li, Chun; Lun, Cheng Man; Majeske, Audrey J; Matranga, Valeria; Nair, Sham V; Rast, Jonathan P; Raftos, David A; Roth, Mattias; Sacchi, Sandro; Schrankel, Catherine S; Stensvåg, Klara

    2010-01-01

    A survey for immune genes in the genome for the purple sea urchin has shown that the immune system is complex and sophisticated. By inference, immune responses of all echinoderms maybe similar. The immune system is mediated by several types of coelomocytes that are also useful as sensors of environmental stresses. There are a number of large gene families in the purple sea urchin genome that function in immunity and of which at least one appears to employ novel approaches for sequence diversification. Echinoderms have a simpler complement system, a large set of lectin genes and a number of antimicrobial peptides. Profiling the immune genes expressed by coelomocytes and the proteins in the coelomic fluid provide detailed information about immune functions in the sea urchin. The importance of echinoderms in maintaining marine ecosystem stability and the disastrous effects of their removal due to disease will require future collaborations between ecologists and immunologists working towards understanding and preserving marine habitats. PMID:21528703

  17. Effect of CD8+ Lymphocyte Depletion on Virus Containment after Simian Immunodeficiency Virus SIVmac251 Challenge of Live Attenuated SIVmac239Δ3-Vaccinated Rhesus Macaques

    OpenAIRE

    Schmitz, Jörn E.; Johnson, R. Paul; McClure, Harold M.; Manson, Kelledy H.; Wyand, Michael S.; Kuroda, Marcelo J.; Lifton, Michelle A.; Khunkhun, Rajinder S.; McEvers, Kimberly J.; Gillis, Jacqueline; Piatak, Michael; Lifson, Jeffrey D.; Grosschupff, Gudrun; Racz, Paul; Tenner-Racz, Klara

    2005-01-01

    Although live attenuated vaccines can provide potent protection against simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus challenges, the specific immune responses that confer this protection have not been determined. To test whether cellular immune responses mediated by CD8+ lymphocytes contribute to this vaccine-induced protection, we depleted rhesus macaques vaccinated with the live attenuated virus SIVmac239Δ3 of CD8+ lymphocytes and then challenged them with SIV...

  18. Effect of Curcumin on Immune Function of Mice

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    To investigate the effect of curcumin on immune function of mice, the effect of curcumin was examined on the proliferation of spleen lymphocytes of mice and the function of phagocytosis of peritoneal macrophage by using MTT test and the expression of the nucleoprotein of NFκB p65 was determined in spleen lymphocytes by employing Western Blot. Our results showed that curcumin could enhance the phagocytosis of peritoneal macrophages. Lowdose curcumin could upregulate the proliferation of spleen lymphocytes of mice, and highdose curcumin could suppress the proliferation of spleen lymphocytes. Curcumin could suppress the expression of NFκB p65. Our study suggested that curcumin can regulate immune function of mice in a dosedependent manner. The possible underlying mechanism might be its ability to suppress the activity of NFκB p65.

  19. Inhibition of cell mediated immune responses by copper, ceruloplasmin and oral contraceptives

    International Nuclear Information System (INIS)

    We have shown that free copper inhibited lymphocyte transformation in the whole blood lymphocyte cultures. Ceruloplasmin also inhibited lymphocyte transformation in the above tests as well as another test involving purified protein derivative from Mycobacterium tuberculosis. Women on oral contraceptives have elevated serum copper and ceruloplasmin levels, as do cancer patients. We hypothesize that women on oral contraceptives may have decreased cell mediated immune responses and may thus be at higher risk for cancer induction

  20. 双胰腺癌相关抗原RNA转染树突细胞诱导特异性抗癌免疫反应的实验研究%Induction of specific immune cytotoxic T lymphocyte responses against pancreatic cancer by transfected dendritic cells with MUC4 and Survivin mRNA in vitro

    Institute of Scientific and Technical Information of China (English)

    陈江; 郭晓钟; 李宏宇; 邵晓东; 许文达

    2014-01-01

    Objective To investigate the induction of specific anti-tumor immune response induced by MUC4 and Survivin mRNA co-transfected dendritic cells (DCs) to provide the experimental evidences for the treatment of human pancreatic cancer with multi-epitope loaded DC vaccine. Methods DCs were isolated and cultured from peripheral blood mononuclear cells (PBMCs). After being transcripted and amplified, MUC4 and Survivin mRNA were co-transfected into DCs by electroporation. The expression of MUC4 and Survivin in DCs were detected by Western blot. The survival rate of transfected DCs were determined by MTT method. The induction of specific CTL activation by MUC4 and Survivin mRNA co-transfected DCs were evaluated through testing released IFN-γ by ELISA method. The induction of specific cytotoxic T lymphocyte (CTL) re-sponse by MUC4 and Survivin mRNA co-transfected DCs were measured by 51Cr standard cytotoxicity test. Results After MUC4 and Survivin mRNA co-transfection for 72 hours, the expression amount of MUC4 and Survivin were lower than the expression amount of MUC4 or Survivin individually. Compared with the MUC4 or Survivin mRNA individual transfected DCs, the IFN-γreleased in 24 hours by CTLs stimulated with MUC4 and Survivin mRNA co-transfection DCs were (33.84 ± 3.51)U/ml which was significantly higher than the amount of (21.87 ± 4.12)U/ml by MUC4 or (16.61 ± 2.09)U/ml by Survivin mRNA individually (P < 0.05). DCs co-transfection with MUC4 and Survivin mRNA could effectively induce HLA-A2 +/MUC4+/Survivin + specific CTL immune responses against pancreatic cancer cells in vitro. Conclusion The induction of CTLs by DCs co-transfected with human pancreatic cancer MUC4 and Survivin mRNA could produce more powerful specific anti-tumor immunity than single antigen loaded DCs.%目的:研究人胰腺癌MUC4与Survivin mRNA联合转染树突细胞(DC)诱导的特异性抗肿瘤免疫反应,为构建负载多抗原表位DC疫苗治疗胰腺癌提供实验依据

  1. Immune checkpoint inhibition in lymphoid disease.

    Science.gov (United States)

    Eyre, Toby A; Collins, Graham P

    2015-08-01

    It has long been understood that the immune system has intrinsic anti-tumour activity in humans, and that a key mechanism of tumour progression is the ability of a tumour to escape this immune surveillance. A number of attempts have been made to harness this anti-tumour immunity in both solid tumour oncology and haematological malignancies with variable success. Examples include the use of allogeneic stem cell transplantation and donor lymphocyte infusion in haematological cancer and vaccine studies in solid tumours. Enhanced signalling of the Programmed cell death-1 (PDCD1, PD-1)/cytotoxic T-lymphocyte-associated protein 4 (CTLA4) 'immune checkpoint' pathway has emerged recently as a critical mechanism by which tumours can escape the natural anti-tumour immune response. As such, novel therapies have been developed to help enhance this natural immunity by switching off the PDCD1/CTLA4 immune checkpoint pathway. The following review will discuss the pathobiology of these pathways and the exciting new data now available in lymphoid malignancies. PMID:25824455

  2. Alteration of membrane phospholipid methylation by adenosine analogs does not affect T lymphocyte activation

    International Nuclear Information System (INIS)

    Membrane phospholipid methylation has been described during activation of various immune cells. Moreover recent data indicated modulation of immune cells functions by adenosine. As S-adenosyl-methionine and S-adenosyl-homocysteine are adenosine analogs and modulators of transmethylation reactions, the effects of SAH and SAM were investigated on membrane phospholipid methylation and lymphocyte activation. SAM was shown to induce the membrane phospholipid methylation as assessed by the 3Hmethyl-incorporation in membrane extract. This effect was inhibited by SAH. In contrast SAM and SAH did not affect the phytohemagglutinin-induced proliferative response of peripheral blood mononuclear cells. SAH neither modified the early internalization of membrane CD3 antigens nor did it prevent the late expression of HLA-DR antigens on lymphocytes activated by phytohemagglutinin. These results indicate that in vitro alteration of phospholipid methylation does not affect subsequent steps of human T lymphocyte activation and proliferation

  3. Significance of tumour mass on T-lymphocyte levels in patients with gastrointestinal cancer.

    Science.gov (United States)

    Shukla, H S; Whitehead, R H; Hughes, L E

    1979-08-01

    The relationship between tumour load and immunity in gastrointestinal cancer has been studied by sequential comparison in patients whose tumour has been removed and those whose tumour was found to be inoperable. Total lymphocyte count, absolute and percentage T- and B-lymphocyte counts, effect of papain on E-rosetting cell levels, and inhibitory effect of cancer sera on E-rosette formation by normal lymphocytes have been studied in 30 patients with stomach or colorectal cancer, and 10 control patients with benign gastrointestinal disease. The examination was done on each patient before and at regular intervals after operation up to 24 weeks. Operable cases, with removal of tumour load, showed a temporary fall in total lymphocyte count and T cell counts, which returned to normal by four weeks postoperatively. Inoperable cases (15 patients) showed a progressive fall in total lymphocyte count and a relatively greater depression of T cell counts, in parallel with increasing tumour mass. E-receptor blocking factor was demonstrated in the sera of cancer patients. This factor was related to tumour mass and presumably was of tumour origin, as it persisted in the inoperable group but disappeared by 12 weeks after tumour removal. The factor explained the excess depresion of T cells over total lymphocytes, but does not explain the continuing depression of total lymphocyte count in the cancer patients. PMID:314923

  4. Analysis of IL-2-like factor in lymphocyte culture supernatant of olive flounder, Paralichthys oliveaceus

    Science.gov (United States)

    Wu, Riqin; Zhang, Peijun; Li, Jun; Xu, Yongli

    2005-03-01

    To study immune mechanism of fish lymphocyte we performed a proliferation assay and ELISA using monoclonal antibody against human IL-2. The result showed that an interleukin-2 (IL-2)-like factor was detected in the supernatant of plant haemoglutinin (PHA)-stimulated lymphocyte culture from peripheral blood, spleen and head kidney of olive flounder, Paralichthys olivaceus. The quantities of IL-2-like factor in the supernatant from different lymphoid tissues were quite different. The IL-2 like factor in the supernatant from cultured head kidney lymphocytes was much higher than those of peripheral blood lymphocytes and spleen lymphocytes ( Precombinant human IL-2, (rhIL-2) was able to stimulate flounder thymocyte proliferation and used to detect the IL-2 receptor (IL-2R) on the surface of flounder lymphocyte. The cross-reaction between the lymphocytes of flounder peripheral blood and CD25(IL-2R) was detected with flow cytometry and shown that the percentage of CD25-positive cell in peripheral blood was 7.74±0.67%.

  5. Immune Exhaustion and Transplantation.

    Science.gov (United States)

    Sanchez-Fueyo, A; Markmann, J F

    2016-07-01

    Exhaustion of lymphocyte function through chronic exposure to a high load of foreign antigen is well established for chronic viral infection and antitumor immunity and has been found to be associated with a distinct molecular program and characteristic cell surface phenotype. Although exhaustion has most commonly been studied in the context of CD8 viral responses, recent studies indicate that chronic antigen exposure may affect B cells, NK cells and CD4 T cells in a parallel manner. Limited information is available regarding the extent of lymphocyte exhaustion development in the transplant setting and its impact on anti-graft alloreactivity. By analogy to the persistence of a foreign virus, the large mass of alloantigen presented by an allograft in chronic residence could provide an ideal setting for exhausting donor-reactive T cells. The extent of T cell exhaustion occurring with various allografts, the kinetics of its development, whether exhaustion is influenced positively or negatively by different immunosuppressants, and the impact of exhaustion on graft survival and tolerance development remains a fertile area for investigation. Harnessing or encouraging the natural processes of exhaustion may provide a novel means to promote graft survival and transplantation tolerance. PMID:26729653

  6. CYTOTOXIC T-LYMPHOCYTE IMMUNOTHERAPY FOR OVARIAN CANCER: A PILOT STUDY

    OpenAIRE

    Wright, Stephen E.; Rewers-Felkins, Kathleen A.; Quinlin, Imelda S.; Phillips, Catherine A.; Townsend, Mary; Philip, Ramila; Dobrzanski, Mark J.; Lockwood-Cooke, Pamela R.; Robinson, William

    2012-01-01

    The objective was to evaluate the toxicity and feasibility of intraperitoneal (IP) infusion of tumor-specific cytotoxic T-lymphocytes (CTL) as therapy for recurrent ovarian cancer, and to determine if repetitive cycles of CTL generation and infusion measurably increases the host’s ovarian cancer immune response.

  7. In vitro effects of plant and mushroom extracts on immunological function of chicken lymphocytes and macrophages

    Science.gov (United States)

    The present study was conducted to examine the effects of milk thistle (Silybum marianum), turmeric (Curcuma longa), reishi mushroom (Ganoderma lucidum), and shiitake mushroom (Lentinus edodes) on innate immunity and tumor cell viability. In vitro culture of chicken spleen lymphocytes with extracts ...

  8. Expression Profiles of Cloned Channel Catfish (Ictalurus punctatus) Lymphoid Cell Lines and Mixed Lymphocyte Cultures

    Science.gov (United States)

    Clonal channel catfish lymphoid cell lines and mixed lymphocyte cultures (MLC) have proven extremely useful in examining immune responses at the cellular and molecular levels. To date clonal catfish cell lines and MLC have been biologically and phenotypically characterized using a variety of techniq...

  9. Characterization of thymus - and bone marrow-derived lymphocytes in rats by means of 3H-uridine incorporation

    International Nuclear Information System (INIS)

    Lymphocytes from various lymphoid oro.ans and from the thoracic duct of normal and thymectomized rats, irradiated and reconstituted with syngeneic bone marrow were tested in vitro in a minimal non-enriched cultivation medium with 3H-uridine, and the percentage of uridine-labelled lymphocytes was determined. The highest number of heavily labelled small lymphocytes was found in the thymus and in the thoracic duct, fewer in peripheral blood, the lymph nodes and the spleen, the smallest number in the bone marrow. The thymectomized animals showed reduced uridine uptake. The method of immune rosette formation was used to determine the presence of B lymphocytes in the lymphoid rat population. The highest quantity of B lymphocytes was recorded in the bone marrow and the least in the thymus and in the thoracic duct. Thymectomized animals had a significantly higher percentage of EAC rosettes than normal and sham-operated animals. The methods employed and existing literary data enabled us to identify the heavily uridine-labelled lymphocytes as T cells, while unlabelled lymphocytes are considered to be B cells. The difference in uridine uptake in rat lymphocytes may serve as one of the T lymphocyte markers in a heterologous lymphoid population. (author)

  10. Effects of environmental stressors on lymphocyte proliferation in Florida manatees, Trichechus manatus latirostris.

    Science.gov (United States)

    Walsh, Cathy J; Luer, Carl A; Noyes, David R

    2005-02-10

    The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected each year by exposure to cold weather or harmful algal blooms (red tide; Karenia brevis). Exposures can be sublethal, resulting in stressed animals that are rescued and taken to authorized facilities for rehabilitation, or lethal if exposures are prolonged or unusually severe. To investigate whether sublethal environmental exposures can impair immune function in manatees, rendering animals vulnerable to disease or death, mitogen-induced proliferation was assessed in lymphocytes from manatees exposed to cold temperatures (N=20) or red tide (N=19) in the wild, and compared to lymphocyte responses from healthy free-ranging manatees (N=32). All animals sampled for this study were adults. Lymphocytes were stimulated in vitro with either concanavalin A (ConA) or phytohemagglutinin (PHA) and proliferation was assessed after 96 h using incorporation of the thymidine analog, bromodeoxyuridine (BrdU), into newly synthesized DNA. Proliferation of lymphocytes from manatees rescued from exposure to red tide or cold-stress was approximately one-third that of lymphocytes from healthy free-ranging manatees. To examine the direct effects of red tide toxins on lymphocyte function, mitogen-induced proliferation was assessed following co-culture of lymphocytes with K. brevis toxin extracts. Stimulation indices decreased with increasing toxin concentration, with a significant decrease in proliferation occurring in the presence of 400 ng red tide toxins/ml. When lymphocytes from cold-stressed manatees were co-cultured with red tide toxin extracts, proliferative responses were reduced even further, suggesting multiple stressors may have synergistic effects on immune function in manatees. PMID:15621310

  11. Peripheral Blood Lymphocyte Depletion After Hepatic Arterial {sup 90}Yttrium Microsphere Therapy for Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Carr, Brian I., E-mail: brianicarr@hotmail.com [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA and Department of Nutrition and Exptl Biology, Saverio De Bellis Medical Research Institute, Castellana Grotte, Bari (Italy); Metes, Diana M. [Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA and Department of Nutrition and Exptl Biology, Saverio De Bellis Medical Research Institute, Castellana Grotte, Bari (Italy)

    2012-03-01

    Purpose: The short- and long-term effects of {sup 90}Yttrium microspheres therapy for hepatocellular carcinoma (HCC) on peripheral blood lymphocytes are unknown and were therefore examined. Methods and Materials: Ninety-two HCC patients were enrolled in a {sup 90}Yttrium therapy study and routine blood counts were examined as part of standard clinical monitoring. Results: We found an early, profound, and prolonged lymphopenia. In a subsequent cohort of 25 additional HCC patients, prospective flow cytometric immune-monitoring analysis was performed to identify specific changes on distinct lymphocyte subsets (i.e., CD3, CD4, CD8 T, and CD19 B lymphocytes) and NK cells absolute numbers, in addition to the granulocytes and platelets subsets. We found that the pretreatment lymphocyte subset absolute numbers (with the exception of NK cells) had a tendency to be lower compared with healthy control values, but no significant differences were detected between groups. Posttherapy follow-up revealed that overall, all lymphocyte subsets, except for NK cells, were significantly (>50% from pretherapy values), promptly (as early as 24 h) and persistently (up to 30 months) depleted post-{sup 90}Yttrium microspheres therapy. In contrast, granulocytes increased rapidly (24 h) to compensate for lymphocyte depletion, and remained increased at 1-year after therapy. We further stratified patients into two groups, according to survival at 1 year. We found that lack of recovery of CD19, CD3, CD8, and especially CD4 T cells was linked to poor patient survival. No fungal or bacterial infections were noted during the 30-month follow-up period. Conclusions: The results show that lymphocytes (and not granulocytes, platelets, or NK cells) are sensitive to hepatic arterial {sup 90}Yttrium without associated clinical toxicity, and lack of lymphocyte recovery (possibly leading to dysregulation of adaptive cellular immunity) posttherapy indicates poor survival.

  12. Peripheral Blood Lymphocyte Depletion After Hepatic Arterial 90Yttrium Microsphere Therapy for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Purpose: The short- and long-term effects of 90Yttrium microspheres therapy for hepatocellular carcinoma (HCC) on peripheral blood lymphocytes are unknown and were therefore examined. Methods and Materials: Ninety-two HCC patients were enrolled in a 90Yttrium therapy study and routine blood counts were examined as part of standard clinical monitoring. Results: We found an early, profound, and prolonged lymphopenia. In a subsequent cohort of 25 additional HCC patients, prospective flow cytometric immune-monitoring analysis was performed to identify specific changes on distinct lymphocyte subsets (i.e., CD3, CD4, CD8 T, and CD19 B lymphocytes) and NK cells absolute numbers, in addition to the granulocytes and platelets subsets. We found that the pretreatment lymphocyte subset absolute numbers (with the exception of NK cells) had a tendency to be lower compared with healthy control values, but no significant differences were detected between groups. Posttherapy follow-up revealed that overall, all lymphocyte subsets, except for NK cells, were significantly (>50% from pretherapy values), promptly (as early as 24 h) and persistently (up to 30 months) depleted post-90Yttrium microspheres therapy. In contrast, granulocytes increased rapidly (24 h) to compensate for lymphocyte depletion, and remained increased at 1-year after therapy. We further stratified patients into two groups, according to survival at 1 year. We found that lack of recovery of CD19, CD3, CD8, and especially CD4 T cells was linked to poor patient survival. No fungal or bacterial infections were noted during the 30-month follow-up period. Conclusions: The results show that lymphocytes (and not granulocytes, platelets, or NK cells) are sensitive to hepatic arterial 90Yttrium without associated clinical toxicity, and lack of lymphocyte recovery (possibly leading to dysregulation of adaptive cellular immunity) posttherapy indicates poor survival.

  13. Age and dose related alteration of in vitro mixed lymphocyte culture response of blood lymphocytes from A-bomb survivors

    International Nuclear Information System (INIS)

    The responsiveness of peripheral blood lymphocytes to allogenic antigens in mixed lymphocyte culture (MLC) was measured in 139 atomic-bomb survivors. The study revealed a significant decrease in MLC response with increasing dose of previous radiation exposure. This decline was marked in the survivors who were older than 15 at the time of the bomb (ATB). The results suggest a possible relationship between the recovery of T-cell-related function and the thymic function which processes mature T cells for the immune system. Thus it may be that in the advanced age ATB group, the thymus function had started to involute, allowing less recovery of T-cell function compared to young survivors who had adequate processing T-cell activity

  14. Immune Response to Electromagnetic Fields through Cybernetic Modeling

    Science.gov (United States)

    Godina-Nava, J. J.; Segura, M. A. Rodríguez; Cadena, S. Reyes; Sierra, L. C. Gaitán

    2008-08-01

    We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen.

  15. Investigation of man's immune system (M112), part B

    Science.gov (United States)

    Ritzmann, S. E.; Levin, W. C.

    1973-01-01

    Fifty-six days of residence in a Skylab-type environment produce essentially no change in the reactivity of the human immune system, as typified by the rate of RNA or DNA synthesis in small lymphocytes. The one point of divergence between the Skylab simulation crew and previous Apollo crews, a marked depression in synthesis rates on the fourteenth day after the chamber study, may be due to some technical difficulty in the experiment. Lymphocyte morphology changes paralleled functional changes.

  16. Immune Response to Electromagnetic Fields through Cybernetic Modeling

    International Nuclear Information System (INIS)

    We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen

  17. Persistent virus infection despite chronic cytotoxic T-lymphocyte activation in gamma interferon-deficient mice infected with lymphocytic choriomeningitis virus

    DEFF Research Database (Denmark)

    Bartholdy, C; Christensen, Jan Pravsgaard; Wodarz, D;

    2000-01-01

    The role of gamma interferon (IFN-gamma) in the permanent control of infection with a noncytopathic virus was studied by comparing immune responses in wild-type and IFN-gamma-deficient (IFN-gamma -/-) mice infected with a slowly invasive strain of lymphocytic choriomeningitis virus (LCMV Armstrong......). While wild-type mice rapidly cleared the infection, IFN-gamma -/- mice became chronically infected. Virus persistence in the latter mice did not reflect failure to generate cytotoxic T-lymphocyte (CTL) effectors, as an unimpaired primary CTL response was observed. Furthermore, while ex vivo CTL activity...

  18. Gastrointestinal T Lymphocytes Retain High Potential for Cytokine Responses but Have Severe CD4+ T-Cell Depletion at All Stages of Simian Immunodeficiency Virus Infection Compared to Peripheral Lymphocytes

    OpenAIRE

    Smit-McBride, Zeljka; Mattapallil, Joseph J.; McChesney, Michael; Ferrick, David; Dandekar, Satya

    1998-01-01

    Gastrointestinal complications in human immunodeficiency virus (HIV) infection are indicative of impaired intestinal mucosal immune system. We used simian immunodeficiency virus (SIV)-infected rhesus macaques as an animal model for HIV to determine pathogenic effects of SIV on intestinal T lymphocytes. Intestinal CD4+ T-cell depletion and the potential for cytokine responses were examined during SIV infection and compared with results for lymphocytes from lymph nodes and blood. Flow cytometri...

  19. In vitro cell-mediated immunity assay using 125I-iododeoxyuridine

    International Nuclear Information System (INIS)

    We investigated an in vitro cell-mediated immunity assay using incorporation of 125I-iododeoxyuridine as an indicator of lymphocyte responsiveness to mitogen stimulation. The system permits the use of whole-blood cultures in rats and dogs

  20. Echinoderm immunity

    OpenAIRE

    JE García-Arrarás; F Ramírez-Gómez

    2010-01-01

    Echinoderms are exclusively marine animals that, after the chordates, represent the second largest group of deuterostomes. Their diverse species composition and singular ecological niches provide at the same time challenges and rewards when studying the broad range of responses that make up their immune mechanisms. Two types of responses comprise the immune system of echinoderms: a cellular response and a humoral one. Cell-based immunity is carried by the celomocytes, a morphologically hetero...

  1. DNA Immunization

    OpenAIRE

    Wang, Shixia; Lu, Shan

    2013-01-01

    DNA immunization was discovered in early 1990s and its use has been expanded from vaccine studies to a broader range of biomedical research, such as the generation of high quality polyclonal and monoclonal antibodies as research reagents. In this unit, three common DNA immunization methods are described: needle injection, electroporation and gene gun. In addition, several common considerations related to DNA immunization are discussed.

  2. Immune Thrombocytopenia

    OpenAIRE

    Kistanguri, Gaurav; McCrae, Keith R

    2013-01-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary form characterized by isolated thrombocytopenia (platelet count < 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia, or a secondary form in which immune thrombocytopenia develops in association with another disorder that is usually immune or infectious. ITP may affect individuals of all ages, with peaks during ...

  3. Treatment Options by Stage (Chronic Lymphocytic Leukemia)

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...

  4. Treatment Option Overview (Chronic Lymphocytic Leukemia)

    Science.gov (United States)

    ... ALL Treatment Childhood AML Treatment Research Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version General Information About Chronic Lymphocytic Leukemia Go to Health Professional Version Key Points Chronic ...

  5. Comparison of T-lymphocyte Subsets and Phenotypes between HIV-positive Subjects and HIV-negative Subjects

    Institute of Scientific and Technical Information of China (English)

    陈小平; 陈观今; 肖斌权; 施文钧; 徐惠芳; 高凯

    2001-01-01

    With the advance of research on HIV/AIDS, CD8 T-lymphocyte is believed to be independently an important immune factor of controlling HIV infection not only in its number but also in its func-tion. Multiple studies on phenotypic markers or surface antigens of lymphocytes show that level of expression of CD25 decrease while that of HLA-DR increased on lymphocytes in HIV-infected individuals compared with that in HIV-negative subjects and that levels of expression of these molecules represent a part of function of lymphocytes. But function testing of CD4 cell and CD8 cell is complicated in technique and time spending. In addition, some studies indicate that apoptosis of CD4 cells play an important role in HIV/AIDS pathogenesis. So it is clinically important to compare the lymphocyte subsets and phenotypes in HIV-positive subjects with those in HIV-negative individuals.

  6. Comparison of T-lymphocyte Subsets and Phenotypes between HIV-positive Subjects and HIV-negative Subjects

    Institute of Scientific and Technical Information of China (English)

    陈小平; 陈观今; 肖斌权; 施文钧; 徐惠芳; 高凯

    2001-01-01

    @@ With the advance of research on HIV/AIDS, CD8 T-lymphocyte is believed to be independently an important immune factor of controlling HIV infection not only in its number but also in its function. Multiple studies on phenotypic markers or surface antigens of lymphocytes show that level of expression of CD25 decrease while that of HIA-DR increased on lymphocytes in HIV-infected individuals compared with that in HIV-negative subjects and that levels of expression of these molecules represent a part of function of lymphocytes. But function testing of CD4 cell and CD8 cell is complicated in technique and time spending. In addition, some studies indicate that apoptosis of CD4 cells play an important role in HIV/AIDS pathogenesis. So it is clinically important to compare the lymphocyte subsets and phenotypes in HIV-positive subjects with those in HIV-negative individuals.

  7. High-definition mapping of retroviral integration sites defines the fate of allogeneic T cells after donor lymphocyte infusion

    OpenAIRE

    Cattoglio, Claudia; Maruggi, Giulietta; Bartholomae, Cynthia; Malani, Nirav; Pellin, Danilo; Cocchiarella, Fabienne; Magnani, Zulma; Ciceri, Fabio; Ambrosi, Alessandro; von Kalle, Christof; Bushman, Frederic D.; Bonini, Chiara; Schmidt, Manfred; MAVILIO, Fulvio; Recchia, Alessandra

    2010-01-01

    The infusion of donor lymphocytes transduced with a retroviral vector expressing the HSV-TK suicide gene in patients undergoing hematopoietic stem cell transplantation for leukemia/lymphoma promotes immune reconstitution and prevents infections and graft-versus-host disease. Analysis of the clonal dynamics of genetically modified lymphocytes in vivo is of crucial importance to understand the potential genotoxic risk of this therapeutic approach. We used linear amplification-mediated PCR and p...

  8. Lymphocyte Reactivity Contributes to Protection Conferred by Specific Antibody Passively Transferred to Herpes Simplex Virus-Infected Mice

    OpenAIRE

    Oakes, John E.; Davis, William B.; Taylor, John A.; Weppner, William A.

    1980-01-01

    Passively acquired immunity to herpes simplex virus (HSV) was studied in antithymocyte serum (ATS)-treated mice and athymic nude mice to determine whether immunocompetent lymphocytes contribute to the protection observed after transfer of HSV-specific antibody to infected animals. Mice were given three intraperitoneal injections of 0.1 ml of ATS at 24-h intervals. This treatment reduced concanavalin A and lipopolysaccharide stimulation of lymphocytes harvested from these animals by 90% when c...

  9. Tumor infiltration by chemokine receptor 7 (CCR7)+ T-lymphocytes is a favorable prognostic factor in metastatic colorectal cancer

    OpenAIRE

    Correale, Pierpaolo; Rotundo, Maria Saveria; Botta, Cirino; del Vecchio, Maria Teresa; Tassone, Pierfrancesco; Tagliaferri, Pierosandro

    2012-01-01

    The immune interactions occurring within the tumor microenvironment have a critical role in determining the outcome of colorectal cancer patients. We carried-out an immunohistochemical analysis of tumor infiltrating T-lymphocytes expressing chemokine receptor 7 (CCR7) in a series of colorectal cancer patients enrolled in a prospective clinical trial. We demonstrated that a high tumor infiltration score of this lymphocyte subset is predictive of longer progression free survival and overall sur...

  10. Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques.

    Science.gov (United States)

    Weed, Michael R; Carruth, Lucy M; Adams, Robert J; Ator, Nancy A; Hienz, Robert D

    2006-09-01

    The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells. PMID:18040802

  11. Apoptosis of circulating lymphocytes during pediatric cardiac surgery

    Science.gov (United States)

    Bocsi, J.; Pipek, M.; Hambsch, J.; Schneider, P.; Tárnok, A.

    2006-02-01

    There is a constant need for clinical diagnostic systems that enable to predict disease course for preventative medicine. Apoptosis, programmed cell death, is the end point of the cell's response to different induction and leads to changes in the cell morphology that can be rapidly detected by optical systems. We tested whether apoptosis of T-cells in the peripheral blood is useful as predictor and compared different preparation and analytical techniques. Surgical trauma is associated with elevated apoptosis of circulating leukocytes. Increased apoptosis leads to partial removal of immune competent cells and could therefore in part be responsible for reduced immune defence. Cardiovascular surgery with but not without cardiopulmonary bypass (CPB) induces transient immunosuppression. Its effect on T-cell apoptosis has not been shown yet. Flow-cytometric data of blood samples from 107 children (age 3-16 yr.) who underwent cardiac surgery with (78) or without (29) CPB were analysed. Apoptotic T-lymphocytes were detected based on light scatter and surface antigen (CD45/CD3) expression (ClinExpImmunol2000;120:454). Results were compared to staining with CD3 antibodies alone and in the absence of antibodies. T-cell apoptosis rate was comparable when detected with CD45/CD3 or CD3 alone, however not in the absence of CD3. Patients with but not without CPB surgery had elevated lymphocyte apoptosis. T-cell apoptosis increased from 0.47% (baseline) to 0.97% (1 day postoperatively). In CPB patients with complication 1.10% significantly higher (ANOVA p=0.01) comparing to CPB patients without complications. Quantitation of circulating apoptotic cells based on light scatter seems an interesting new parameter for diagnosis. Increased apoptosis of circulating lymphocytes and neutrophils further contributes to the immune suppressive response to surgery with CPB. (Support: MP, Deutsche Herzstiftung, Frankfurt, Germany)

  12. Splenic lymphocyte immune response induced by recombinant Toxoplasma gondii phosphoglycerate mutase 2 in combination with interleukin-2 or interferon γin mice%重组弓形虫磷酸甘油酸变位酶2联合白细胞介素-2或干扰素γ诱导小鼠的脾淋巴细胞免疫应答

    Institute of Scientific and Technical Information of China (English)

    李雅清; 王海龙; 祝建疆; 孟晓丽; 杨建一; 殷国荣

    2013-01-01

    Objective To observe the splenic lymphocyte immune response induced by intranasal immunization with recombinant Toxoplasma gondii phosphoglycerate mutase 2 (rTgPGAM2) in combination with interleukin-2 (IL-2) or interferon γ (IFNγ) in mice, and investigate the adjuvant effects of IL-2 and IFN γ. Methods Forty-eight BALB/c mice were randomly divided into six groups and immunized with 30 μg rTgPGAM2, 500 IU IL-2, 1 000 IU IFNγ, 30 μg rT-gPGAM2 + 500 IU IL-2, 30 μg rTgPGAM2 + 1 000 IU IFN7 and 20 μl PBS (control) respectively for 3 times by intranasal drip. The interval between the first and the second doses was 2 weeks, while that between the second and the third doses was one week. The mice were killed on day 14 after the third immunization, of which the proliferation activity of splenic lymphocytes were determined by CCK-8 method, and the IL-2, IFN7, IL-4 and IL-10 levels in culture supernatant of splenic lymphocytes by ELISA. Results After stimulation with rTgPGAM2, the stimulation indexes (Sis) of splenic lymphocytes of mice were significantly higher in five test groups than in control group (P < 0. 05 or P < 0. 01), and in rTgPGAM2 + IL-2 and rTgPGAM2 + IFNγ groups than in rTgPGAM2 group (P < 0. 01 or P < 0. 05). However,after stimulation with ConA, only the SI in IL-2 group was higher than that in control group (P < 0. 01). The IL-2 and IFNγ levels in culture supernatant of splenic lymphocytes were significantly higher in test groups than in control group (P < 0. 05), and in rTgPGAM2 + IL-2 and rTgPGAM2 + IFN7 groups than in rTgPGAM2 group(P < 0. 01 or P < 0. 05). The IL-4 levels in rTgPGAM2, rTgPGAM2 + IL-2 and rTgPGAM2 + IFNγ groups were significantly higher than that in control group (P < 0. 05). However, only the IL-10 levels in IFNγ and rTgPGAM2 + IFNγ groups were significantly higher than that in control group (P < 0. 05). Conclusion The splenic lymphocyte immune response induced in mice by intranasal immunization with r

  13. Age-Related Differences in Percentages of Regulatory and Effector T Lymphocytes and Their Subsets in Healthy Individuals and Characteristic STAT1/STAT5 Signalling Response in Helper T Lymphocytes

    Directory of Open Access Journals (Sweden)

    Marija Holcar

    2015-01-01

    Full Text Available The dynamic process of the development of the immune system can in itself result in age-related immune malfunctions. In this study, we analysed lymphocyte subsets in the peripheral blood of 60 healthy donors, divided into groups of children, adolescents, and adults, focusing on effector (Teff and regulatory (Treg T lymphocytes and STAT1/STAT5 signalling response in helper T lymphocytes (Th in adults, using flow cytometry. Our results demonstrate a decrease in the percentage of total Tregs and an increase in the percentage of total Teffs with age and a consequential immense increase in the Teff/Treg ratio. The increase of Teffs was most apparent in Th1, Th1Th17, and Th17CD161− subsets. Significant Th lymphocyte STAT1 expression differences were observed between children and adolescents, which were associated with the decrease in activated Tregs. Higher expression of STAT1 was found in FoxP3hi than in FoxP3low Th lymphocytes, while significant IL-2 induced STAT5 phosphorylation differences were found among the subsets of Th lymphocytes in adults. Our study demonstrates age-related changes in circulating Teff and Treg, as well as significant differences in STAT5/STAT1 signalling among FoxP3+ Th lymphocytes, providing new advances in the understanding of immunosenescence.

  14. Hematopoietic stem and progenitor cells in HIV/AIDS and immune reconstitution

    Institute of Scientific and Technical Information of China (English)

    Jielin Zhang; Clyde S Crumpacker

    2010-01-01

    @@ The human immunodeficiency virus type 1 (HIV-1) causes an acquired immunodeficiency syndrome (AIDS).HIV-1 infects human immune cells,specifically CD4+ lymphocytes, which leads to AIDS and undermines reconstitution of immunity. The unique challenges of HIV/AIDS have triggered multidisciplinary investigators to study the virology of the pathogen and the biology of the host cells, especially the interactions of HIV-1 with T-lymphocytes,macrophages, and hematopoietic stem and progenitor cells (HSPC) [1-8].

  15. Immune modulation following immunization with polyvalent vaccines in dogs.

    Science.gov (United States)

    Strasser, Alois; May, Bettina; Teltscher, Andrea; Wistrela, Eva; Niedermüller, Hans

    2003-08-15

    A decline in T-cell-mediated immunity and transient state of immunosuppression after immunization has been reported in dogs. Nevertheless, dogs are still routinely vaccinated with polyvalent live vaccines and severe disease does not generally occur. In order to investigate these effects on the canine immune system and to elucidate possible mechanisms we determined the following immune parameters in the blood of 33 clinically sound German shepherd dogs before and after standard vaccination with a polyvalent vaccine against distemper, parvovirus, viral hepatitis, leptospirosis, kennel cough and rabies: white and differential blood cell count, the serum concentrations and/or activities of IL-1, IL-2, IFN-gamma, TNF-alpha, neopterin and IgG, natural killer (NK) cell activity, bactericidal activity and complement hemolytic activity, lymphocyte proliferation test (LPT) and nitroblue tetrazolium test (NBT). Our major findings were that significant postvaccinal decreases in T-cell mitogenic response to PHA and in neutrophil function and neopterin serum concentration were accompanied by simultaneous increase in plasma IgG and hemolytic complement activity. This suggests a transient shift in the balance between cell-mediated and humoral (T(H)1/T(H)2) immunity rather than immunosuppression. These results do not imply that dogs should not receive live vaccines, as the response to vaccines just seems to create a state of altered homeostasis when immunization elicits protection by humoral and cell-mediated immunity. However, these recognized compromises of immune function should be considered and vaccines still be applied only in healthy animals and strictly according to the rules and regulations given by the manufacturer. PMID:12909408

  16. Lymphocyte receptors for pertussis toxin

    International Nuclear Information System (INIS)

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes

  17. The course of lymphocytic hypophysitis.

    Science.gov (United States)

    Bitton, R N; Slavin, M; Decker, R E; Zito, J; Schneider, B S

    1991-07-01

    A 27-year-old woman presented to our institution in her seventh month of pregnancy with complaints of headache and visual field disturbance. Workup revealed bitemporal hemianopia, a markedly enlarged pituitary gland on computed tomography scan, and biochemical evidence of partial hypopituitarism. At surgery, a biopsy specimen of the pituitary gland was taken revealing lymphocytic hypophysitis. The patient was treated with steroids and replacement doses of thyroid hormone. Visual fields improved postoperatively. A repeat computed tomography scan obtained 2 months after an uneventful pregnancy showed that her pituitary had regained normal size and contour. Over the next 9 months she had gradual recovery of all pituitary function. This case allowed us to follow and document the course of lymphocytic hypophysitis from its presentation as a macroadenoma with partial hypopituitarism to full recovery of both size and hormonal function of the pituitary. Lymphocytic hypophysitis should be considered in the differential diagnosis of a pituitary mass or pituitary dysfunction presenting in pregnancy. In patients with suspected lymphocytic hypophysitis and a pituitary mass, a trial of steroids may be therapeutic. PMID:2053072

  18. Radiosensitivity of lymphocytes among Filipinos: final report

    International Nuclear Information System (INIS)

    This report is about the studies on the radiosensitivity of Filipino lymphocytes to radiation that can elucidate on the potential of blood chromosomes as biological dosimeters. The objective of this study is to determine the radiosensitivity of lymphocytes among Filipinos and to establish the radiation-induced chromosome anomaly standard curve in lymphocytes for radiological dosimetry. 47 refs., 9 figs., 1 tab

  19. Growing B Lymphocytes in a Three-Dimensional Culture System

    Science.gov (United States)

    Wu, J. H. David; Bottaro, Andrea

    2010-01-01

    A three-dimensional (3D) culture system for growing long-lived B lymphocytes has been invented. The capabilities afforded by the system can be expected to expand the range of options for immunological research and related activities, including testing of immunogenicity of vaccine candidates in vitro, generation of human monoclonal antibodies, and immunotherapy. Mature lymphocytes, which are the effectors of adaptive immune responses in vertebrates, are extremely susceptible to apoptotic death, and depend on continuous reception of survival-inducing stimulation (in the forms of cytokines, cell-to-cell contacts, and antigen receptor signaling) from the microenvironment. For this reason, efforts to develop systems for long-term culture of functional, non-transformed and non-activated mature lymphocytes have been unsuccessful until now. The bone-marrow microenvironment supports the growth and differentiation of many hematopoietic lineages, in addition to B-lymphocytes. Primary bone-marrow cell cultures designed to promote the development of specific cell types in vitro are highly desirable experimental systems, amenable to manipulation under controlled conditions. However, the dynamic and complex network of stromal cells and insoluble matrix proteins is disrupted in prior plate- and flask-based culture systems, wherein the microenvironments have a predominantly two-dimensional (2D) character. In 2D bone-marrow cultures, normal B-lymphoid cells become progressively skewed toward precursor B-cell populations that do not retain a normal immunophenotype, and such mature B-lymphocytes as those harvested from the spleen or lymph nodes do not survive beyond several days ex vivo in the absence of mitogenic stimulation. The present 3D culture system is a bioreactor that contains highly porous artificial scaffolding that supports the long-term culture of bone marrow, spleen, and lymph-node samples. In this system, unlike in 2D culture systems, B-cell subpopulations developing

  20. NEW ASPECTS OF ANTI-INFECTION IMMUNITY

    Directory of Open Access Journals (Sweden)

    E. P. Kisseleva

    2011-01-01

    Full Text Available Abstract. Four types of adaptive immune response which are regulated by different T-cell populations, namely Th1, Th2, Th17 and T regs have been described. At the first time classification is based on the difference in transcription factors but not due to diversity of cytokines produced. Each population of T-lymphocytes possesses a set of unique transcription factors and directions of cell signaling. Each type of immune responses plays a key role in the protection against certain types of pathogens. The Th1-response is important against intracellular bacteria and fungi, the Th17 — against extracellular, the Th2 — against yeasts and protozoa. T-regulatory cells control all types of immune responses. Diversity of immune response mechanisms occurs due to involvement of different effector cells. The Th1-type of response is connected with macrophage activation, Th2-cells cooperate with B-lymphocytes as well as attract eosinophils and mast cells. Th17 lymphocytes stimulate neutrophils and epithelial cells. T-cell differentiation is directed by the cytokines produced by innate immune cells. Phagocytes recognize molecular patterns at the surface of pathogens via pattern-recognition receptors (PRR, become activated and synthesize cytokines. Pathogen plays important role in this process while instructing dendritic cells. Pathogen dials a special code from a number of phagocyte surface receptors, which is named as «combinatory» recognition. Phagocytes possess several different types of activation and synthesize different cytokines that direct T-lymphocytes to a certain type of differentiation.

  1. The effects of phototherapy on the numbers of circulating natural killer cells and T lymphocytes in psoriasis.

    LENUS (Irish Health Repository)

    Tobin, A M

    2009-04-01

    The innate immune system is believed to be important in the pathogenesis of psoriasis and natural killer (NK) have been found in increased numbers in psoriatic plaques. Alterations in the numbers of NK cells in peripheral blood have been reported. We investigated the effect of phototherapy on levels of peripheral NK cells and lymphocytes in patients with psoriasis. In nine patients whom we followed before, during and after narrowband ultraviolet B (UVB) treatment there were no differences in the numbers of circulating lymphocytes, lymphocyte subsets or cells expressing NK markers and controls. Treatment with narrowband UVB did, however, significantly lower circulating CD4 counts which gradually recovered posttreatment.

  2. Comparison of protein and DNA synthesis assays of guinea pig spleen lymphocytes after stimulation with influenza virus antigen and phytohemagglutinin

    International Nuclear Information System (INIS)

    Two in vitro methods for the demonstration of cell-mediated immune response are compared: Protein and DNA synthesis for detection of in vitro influenza virus antigen- and mitogen-induced lymphocyte stimulation. Guinea pig spleen lymphocytes sensitized with influenza virus antigen were tested in a microadaptation of the lymphocyte transformation test using 14C- or 3H-leucine and 3H-thymidine. As a positive control for T-cell stimulation phytohemagglutinin (PHA)-induced lymphocyte stimulation was measured. The following results were obtained: 1. Kinetics of the incorporation of 14C-leucine and 3H-thymidine in lymphocytes incubated with optimal and suboptimal PHA-doses respectively are quantitatively similar but different in time. 2. The results of the protein and DNA synthesis stimulation assays were correlated against influenza virus antigens. 3. The administration of influenza virus antigens in complete Freund's adjuvant induced a more intensive cell-mediated reaction than injections of antigens in aqueous suspensions, but the results of both methods of cell-mediated immune response (CMI) were correlated. 4. The optimal CMI under the experimental cinditions described is induced by an administration of 30 to 50 μg virus protein per animal and by a combined intramuscular - intraperitoneal immunization procedure. 5. The measurement of the early stimulation of protein synthesis in the protein synthesis stimulation test is substantially more rapid than for the classical lymphocyte transformation test. (author)

  3. Immunomodulation by neutrophil myeloperoxidase and hydrogen peroxide: differential susceptibility of human lymphocyte functions.

    Science.gov (United States)

    el-Hag, A; Lipsky, P E; Bennett, M; Clark, R A

    1986-05-01

    The coexistence of activated polymorphonuclear leukocytes and lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. To test this hypothesis, we examined the effects of neutrophil myeloperoxidase and H2O2 on lymphocytes. Human peripheral blood mononuclear leukocytes were exposed to myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase), and a halide, and were then tested for functional activities. Natural killer activity against K562 cells, lymphocyte proliferation in response to mitogens, and generation of immunoglobulin-secreting cells were all susceptible to oxidative injury by myeloperoxidase and H2O2. The degree as well as the mechanism of suppression was dependent on the glucose oxidase concentration (i.e., the rate of H2O2 delivery). At low H2O2 flux, myeloperoxidase was essential for induction of lymphocyte suppression; as the rate of H2O2 generation increased, suppression became myeloperoxidase-independent and was mediated by H2O2 alone. Various lymphocyte functions were differentially susceptible to oxidative injury by myeloperoxidase and H2O2. The proliferative response to poke-weed mitogen was the least sensitive, whereas antibody formation was the most sensitive. Proliferative responses to concanavalin A and phytohemagglutinin as well as natural killer activity displayed intermediate degrees of susceptibility. In all assays, lymphocyte viability was greater than 90%. Removal of monocytes from mononuclear leukocytes by adherence to glass increased susceptibility of lymphocytes to oxidative injury. Monocytes in proportions within the range present in peripheral blood mononuclear leukocytes protected lymphocyte functions against oxidative injury by myeloperoxidase and H2O2. This study demonstrates a differential susceptibility of various immune functions to oxidative injury by the neutrophil products myeloperoxidase and H2O2, and shows, in

  4. Desensitization oft lymphocyte function by CXCR3 ligands in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yu-Qing Liu; Ronnie T. Poon; Jeremy Hughes; Qin-Yu Li; Wan-Ching Yu; Sheung-Tat Fan

    2005-01-01

    CD4+ and CD8+ T cells from HCC patients exhibited diminished chemotactic responses to IP-10 in vitro compared to T cells from healthy control subjects.CONCLUSION: This study demonstrates functional desensitization of the chemokine receptor CXCR3 in lymphocytes from HCC patients by CXCR3 ligands secreted by tumor cells. This may cause lymphocyte dysfunction and subsequently impaired immune defense against the tumor.

  5. CHARACTERISTICS OF SIGNALING PATHWAYS MEDIATING A CYTOTOXIC EFFECT OF DENDRITIC CELLS UPON ACTIVATED Т LYMPHOCYTES AND NK CELLS

    Directory of Open Access Journals (Sweden)

    T. V. Tyrinova

    2014-07-01

    Full Text Available Abstract. Cytotoxic/pro-apoptogenic effects of IFNα-induced dendritic cells (IFN-DCs directed against Т-lymphocytes and NK cells were investigated in healthy donors. Using an allogenic MLC system, it was revealed that IFN-DCs induce apoptosis of both activated CD4+ and CD8+ T-lymphocytes, and NK cells. Apoptosis of CD4+ and CD8+ T-lymphocytes induced by their interaction with IFN-DCs was mediated by various signaling pathways. In particular, activated CD4+Т-lymphocytes were most sensitive to TRAIL- и Fas/ FasL-transduction pathways, whereas activated CD8+ T-lymphocytes were induced to apoptosis via TNFα-mediated pathway. PD-1/B7-H1-signaling pathway also played a distinct role in cytotoxic activity of IFNDCs towards both types of T lymphocytes and activated NK cells. The pro-apoptogenic/cytotoxic activity of IFN-DC against activated lymphocytes may be regarded as a mechanism of a feedback regulation aimed at restriction of immune response and maintenance of immune homeostasis. Moreover, upregulation of proapoptogenic molecules on DCs under pathological conditions may lead to suppression of antigen-specific response, thus contributing to the disease progression.

  6. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    Science.gov (United States)

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  7. Ibrutinib or Idelalisib in Treating Patients With Persistent or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma After Donor Stem Cell Transplant

    Science.gov (United States)

    2016-04-08

    Chronic Lymphocytic Leukemia; Non-Hodgkin Lymphoma; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Small Lymphocytic Lymphoma

  8. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  9. Evolution of B Cell Immunity

    OpenAIRE

    Parra, David; Takizawa, Fumio; Sunyer, J Oriol

    2013-01-01

    Two types of adaptive immune strategies are known to have evolved in vertebrates: the VLR-based system, which is present in jawless organisms and is mediated by VLRA and VLRB lymphocytes, and the BCR/TCR-based system, which is present in jawed species and is provided by B and T cell receptors expressed on B and T cells, respectively. Here we summarize features of B cells and their predecessors in the different animal phyla, focusing the review on B cells from jawed vertebrates. We point out t...

  10. Space flight and the immune system

    Science.gov (United States)

    Cogoli, A.

    1993-01-01

    Depression of lymphocyte response to mitogens in cosmonauts after space flight was reported for the first time in the early 1970s by Soviet immunologists. Today we know that depression of lymphocyte function affects at least 50% of space crew members. Investigations on the ground on subjects undergoing physical and psychological stress indicate that stress is a major factor in immune depression of astronauts. This is despite the fact that weightlessness per se has a strong inhibitory effect on lymphocyte activation in vitro. Although the changes observed never harmed the health of astronauts, immunological changes must be seriously investigated and understood in view of long-duration flight on space stations in an Earth orbit, to other planets such as Mars and to the Moon.

  11. Paucity of CD4+ natural killer T (NKT lymphocytes in sooty mangabeys is associated with lack of NKT cell depletion after SIV infection.

    Directory of Open Access Journals (Sweden)

    Namita Rout

    Full Text Available Lack of chronic immune activation in the presence of persistent viremia is a key feature that distinguishes nonpathogenic simian immunodeficiency virus (SIV infection in natural hosts from pathogenic SIV and HIV infection. To elucidate novel mechanisms downmodulating immune activation in natural hosts of SIV infection, we investigated natural killer T (NKT lymphocytes in sooty mangabeys. NKT lymphocytes are a potent immunoregulatory arm of the innate immune system that recognize glycolipid antigens presented on the nonpolymorphic MHC-class I-like CD1d molecules. In a cross-sectional analysis of 50 SIV-negative and 50 naturally SIV-infected sooty mangabeys, ligand alpha-galactosylceramide loaded CD1d tetramers co-staining with Valpha24-positive invariant NKT lymphocytes were detected at frequencies >or=0.002% of circulating T lymphocytes in approximately half of the animals. In contrast to published reports in Asian macaques, sooty mangabey NKT lymphocytes consisted of CD8(+ and CD4/CD8 double-negative T lymphocytes that were CXCR3-positive and CCR5-negative suggesting that they trafficked to sites of inflammation without being susceptible to SIV infection. Consistent with these findings, there was no difference in the frequency or phenotype of NKT lymphocytes between SIV-negative and SIV-infected sooty mangabeys. On stimulation with alpha-galactosylceramide loaded on human CD1d molecules, sooty mangabey NKT lymphocytes underwent degranulation and secreted IFN-gamma, TNF-alpha, IL-2, IL-13, and IL-10, indicating the presence of both effector and immunoregulatory functional capabilities. The unique absence of CD4(+ NKT lymphocytes in sooty mangabeys, combined with their IL-10 cytokine-secreting ability and preservation following SIV infection, raises the possibility that NKT lymphocytes might play a role in downmodulating immune activation in SIV-infected sooty mangabeys.

  12. Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate.

    Science.gov (United States)

    Hanyuda, Akiko; Ogino, Shuji; Qian, Zhi Rong; Nishihara, Reiko; Song, Mingyang; Mima, Kosuke; Inamura, Kentaro; Masugi, Yohei; Wu, Kana; Meyerhardt, Jeffrey A; Chan, Andrew T; Fuchs, Charles S; Giovannucci, Edward L; Cao, Yin

    2016-08-15

    Higher body mass index (BMI), higher body adiposity and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). Utilizing duplication-method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score, or T-cell [CD3(+) , CD8(+) , CD45RO (PTPRC)(+) or FOXP3(+) ] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person-years), we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (Ptrend   0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor. PMID:27037951

  13. Clinical evaluation of systemic and local immune responses in cancer: time for integration

    OpenAIRE

    Gutkin, Dmitriy W.; Shurin, Michael R.

    2013-01-01

    The immune system has a dual role in cancer development and progression. On the one hand, it can eradicate emerging malignant cells, but on the other hand, it can actively promote growth of malignant cells, their invasive capacities and their ability to metastasize. Immune cells with predominantly anti-tumor functionality include cells of the innate immune system, such as natural killer cells, and cells of adaptive immunity, such as conventional dendritic cells and cytotoxic T lymphocytes. Im...

  14. Phagocyte NADPH oxidase and specific immunity.

    Science.gov (United States)

    Cachat, Julien; Deffert, Christine; Hugues, Stephanie; Krause, Karl-Heinz

    2015-05-01

    The phagocyte NADPH oxidase NOX2 produces reactive oxygen species (ROS) and is a well-known player in host defence. However, there is also increasing evidence for a regulatory role of NOX2 in adaptive immunity. Deficiency in phagocyte NADPH oxidase causes chronic granulomatous disease (CGD) in humans, a condition that can also be studied in CGD mice. Clinical observations in CGD patients suggest a higher susceptibility to autoimmune diseases, in particular lupus, idiopathic thrombocytopenic purpura and rheumatoid arthritis. In mice, a strong correlation exists between a polymorphism in a NOX2 subunit and the development of autoimmune arthritis. NOX2 deficiency in mice also favours lupus development. Both CGD patients and CGD mice exhibit increased levels of immunoglobulins, including autoantibodies. Despite these phenotypes suggesting a role for NOX2 in specific immunity, mechanistic explanations for the typical increase of CGD in autoimmune disease and antibody levels are still preliminary. NOX2-dependent ROS generation is well documented for dendritic cells and B-lymphocytes. It is unclear whether T-lymphocytes produce ROS themselves or whether they are exposed to ROS derived from dendritic cells during the process of antigen presentation. ROS are signalling molecules in virtually any cell type, including T- and B-lymphocytes. However, knowledge about the impact of ROS-dependent signalling on T- and B-lymphocyte phenotype and response is still limited. ROS might contribute to Th1/Th2/Th17 cell fate decisions during T-lymphocyte activation and might enhance immunoglobulin production by B-lymphocytes. In dendritic cells, NOX2-derived ROS might be important for antigen processing and cell activation. PMID:25760962

  15. Echinoderm immunity

    Directory of Open Access Journals (Sweden)

    JE García-Arrarás

    2010-09-01

    Full Text Available Echinoderms are exclusively marine animals that, after the chordates, represent the second largest group of deuterostomes. Their diverse species composition and singular ecological niches provide at the same time challenges and rewards when studying the broad range of responses that make up their immune mechanisms. Two types of responses comprise the immune system of echinoderms: a cellular response and a humoral one. Cell-based immunity is carried by the celomocytes, a morphologically heterogeneous population of free roaming cells that are capable of recognizing and neutralizing pathogens. Celomocytes present diverse morphologies and functions, which include phagocytosis, encapsulation, clotting, cytotoxicity, wound healing among others. Humoral immunity is mediated by a wide variety of secreted compounds that can be found in the celomic fluid and play important roles in defense against infection. Compounds such as lectins, agglutinins, perforins, complement and some cytokines make up some of the humoral responses of echinoderms. Recent advances in the field of molecular biology, genomics and transcriptomics have allowed for the discovery of new immune genes and their products. These discoveries have expanded our knowledge of echinoderm immunity and are setting up the stage for future experiments to better understand the evolution of the immune mechanisms of deuterostomes

  16. Immunity booster

    International Nuclear Information System (INIS)

    The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae558) and of the Gram-negative ones (Klebsiella pneumoniae 507); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as food

  17. The short effect of pelvic radiotherapy of gynecological cancers on humoral and cell mediated immunity

    International Nuclear Information System (INIS)

    An analysis of short effect of pelvic irradiation on cellular and humoral immunity was made in 24 patients treated by irradiation alone or a combination of surgery and irradiation for uterine carcinoma, at 2, 6, 12 months after loco-regional therapy. Twelve months later there is a decrease of T lymphocytes (P = 0.01), whereas the B lymphocytes count is normal; the percentage of T and B lymphocytes remains stable, but the lymphocyte response to PHA after 3 days is reduced (p = 0.03). A significant decrease of immunoglobulins G, A and M is observed

  18. Protection Against Lung Cancer Patient Plasma-Induced Lymphocyte Suppression by Ganoderma Lucidum Polysaccharides

    Directory of Open Access Journals (Sweden)

    Li-Xin Sun

    2014-01-01

    Full Text Available Background/Aims: This study was conducted to determine the potential of Ganoderma lucidum polysaccharides (Gl-PS in protection against lung cancer patient plasma-induced suppression of lymphocytes. Lung cancer is a major cause of disease and loss of life in the United States and worldwide. Cancer cells release immunosuppressive mediators, such as PGE2, TGF-β, IL-10, and VEGF, to inhibit the immune response to escape from immune surveillance. Gl-PS has been shown to counteract this immune inhibition in an animal cell culture model, and thus to facilitate tumor control. The present study explored whether or not such an effect could also be demonstrated in human lung cancer patients. Methods: Immunofluorescence, flow cytometry, MTT, immunocytochemistry, and western blot analysis were used to assess lymphocyte activation with PHA. Results: The plasma of lung cancer patients suppressed proliferation, CD69 expression, and perforin and granzyme B production in lymphocytes upon activation by PHA, effects that were partially of fully reversed by Gl-PS. Conclusion: Lung cancer patient plasma-induced suppression of lymphocyte activation by phytohemagglutinin may be antagonized fully or partially by Gl-PS, an observation suggesting the potential of Gl-PS in cancer therapy.

  19. Imaging B lymphocytes in autoimmune inflammatory diseases

    International Nuclear Information System (INIS)

    B cells arise from stem cells precursor and develop through a tightly regulated and selective process that lead to the generation of different B cell populations such as transitional, mature, memory and plasma cells. These B cell subsets can be identified using flow cytometry by the expression of specific surface antigens. The growing knowledge of the pivotal role played by B cells in the development and progression of autoimmune diseases combined with the advances in monoclonal antibody technology, led in the last years to the generation of different biological agents targeting B cells. In this context, nuclear medicine can offer the possibility to use a panel of biologic radiopharmaceuticals for molecular imaging of inflammatory diseases. Radiopharmaceuticals bind to their targets with high affinity and specificity and have an excellent imaging diagnostic potential for the evaluation of disease activity, selection and monitoring of immune therapies. Several molecules have been radiolabelled for the imaging of T lymphocytes whereas, by now, the anti CD20 rituximab is the only biological therapy targeting B cells that demonstrated to be efficiently radiolabelled and used to detect inflammation in autoimmune patients

  20. Mechanisms of T Lymphocyte Activation Exposed by Super Resolution Microscopy

    Science.gov (United States)

    Campanello, Leonard; Losert, Wolfgang; Traver, Maria; Schaefer, Brian; York, Andrew; Schroff, Hari

    In order to avoid the deleterious consequences of an uncontrolled immune response, tight regulatory control of positive and negative regulators during lymphocyte activation is needed. Utilizing cutting-edge super-resolution imaging technologies in combination with quantitative image analysis we explore the interplay between positive and negative regulation in activated T lymphocytes and investigate whether intercellular signaling is possibly governed by the degradation of a complex intracellular structure called the POLKADOTS signalosome. In segmenting the POLKADOTS signalosome structure by the betweenness centrality of its 3D medial axis skeleton, it was discovered that autophagosomes, small degradative intracellular organelles, localize preferentially to the ends of the filamentous POLKADOTS signalosome. These results provide new insight into the mechanisms behind the complex regulatory process that govern T lymphocyte activation. This research was supported by an Irvington Postdoctoral Fellowship from the Cancer Research Institute (awarded to MT) and a U01 Grant from the National Institutes of Health (GM109887-01, awarded to BS and WL).

  1. Cell-extrinsic defective lymphocyte development in Lmna(-/- mice.

    Directory of Open Access Journals (Sweden)

    J Scott Hale

    Full Text Available BACKGROUND: Mutations in the LMNA gene, which encodes all A-type lamins, result in a variety of human diseases termed laminopathies. Lmna(-/- mice appear normal at birth but become runted as early as 2 weeks of age and develop multiple tissue defects that mimic some aspects of human laminopathies. Lmna(-/- mice also display smaller spleens and thymuses. In this study, we investigated whether altered lymphoid organ sizes are correlated with specific defects in lymphocyte development. PRINCIPAL FINDINGS: Lmna(-/- mice displayed severe age-dependent defects in T and B cell development which coincided with runting. Lmna(-/- bone marrow reconstituted normal T and B cell development in irradiated wild-type recipients, driving generation of functional and self-MHC restricted CD4(+ and CD8(+ T cells. Transplantation of Lmna(-/- neonatal thymus lobes into syngeneic wild-type recipients resulted in good engraftment of thymic tissue and normal thymocyte development. CONCLUSIONS: Collectively, these data demonstrate that the severe defects in lymphocyte development that characterize Lmna(-/- mice do not result directly from the loss of A-type lamin function in lymphocytes or thymic stroma. Instead, the immune defects in Lmna(-/- mice likely reflect indirect damage, perhaps resulting from prolonged stress due to the striated muscle dystrophies that occur in these mice.

  2. Immunity challenge.

    Science.gov (United States)

    Davenport, R John

    2003-06-11

    As people get older, their immune systems falter. The elderly are more susceptible to infections than youngsters are, and hyperactive inflammatory responses appear to contribute to some age-associated illnesses, including Alzheimer's disease and atherosclerosis. Investigating the effect of aging on the immune system was once a scientific stepchild, but card-carrying immunologists are now tackling the problem head-on. Despite the immune system's complexity, researchers have started to make sense of how its components change with age. As the research progresses, scientists hope to bolster elderly people's response to infectious diseases and quiet the inflammation that can make aging a painful experience. PMID:12844525

  3. Mannose receptor is a novel ligand for L-selectin and mediates lymphocyte binding to lymphatic endothelium.

    Science.gov (United States)

    Irjala, H; Johansson, E L; Grenman, R; Alanen, K; Salmi, M; Jalkanen, S

    2001-10-15

    Continuous lymphocyte recirculation between blood and lymphoid tissues forms a basis for the function of the immune system. Lymphocyte entrance from the blood into the tissues has been thoroughly characterized, but mechanisms controlling lymphocyte exit from the lymphoid tissues via efferent lymphatics have remained virtually unknown. In this work we have identified mannose receptor (MR) on human lymphatic endothelium and demonstrate its involvement in binding of lymphocytes to lymphatic vessels. We also show that the binding requires L-selectin, and L-selectin and MR form a receptor-ligand pair. On the other hand, L-selectin binds to peripheral lymph node addressins (PNAds) on high endothelial venules (HEVs) that are sites where lymphocytes enter the lymphatic organs. Interestingly, MR is absent from HEVs and PNAds from lymphatic endothelium. Thus, lymphocyte L-selectin uses distinct ligand molecules to mediate binding at sites of lymphocyte entrance and exit within lymph nodes. Taken together, interaction between L-selectin and MR is the first molecularly defined mechanism mediating lymphocyte binding to lymphatic endothelium. PMID:11602634

  4. Synthesis of antibodies to hepatitis B virus by cultured lymphocytes from chronic hepatitis B surface antigen carriers

    International Nuclear Information System (INIS)

    It has been postulated that host immune defects are responsible for the development and persistence of the hepatitis B surface antigen (HBsAg) carrier state. The synthesis of both anti-HBs and antibody to hepatitis B core antigen (anti-HBc) in cultures containing peripheral blood mononuclear cells from chronic HBsAg carriers and from control (antibody-positive) patients was measured in the presence of pokeweed mitogen. Similar amounts of polyclonal IgG and IgM were synthesized by cultures containing lymphocytes from chronic carriers and controls. Anti-HBc was detectable in lymphocyte supernatants from 2 of 20 controls and from 21 of 29 carriers. The presence of anti-HBc synthesis in vitro correlated with high serum titers of anti-HBc. In contrast, anti-HBs was detected in lymphocyte supernatants from 6 of 20 controls (predominantly in those who had high serum titers of anti-HBs) but in none of the supernatants from 29 HBsAg carriers. Co-culture experiments were performed using T and B lymphocyte fractions that had been purified by affinity chromatography. B lymphocytes from carriers co-cultured with allogeneic irradiated (''helper'') T lymphocytes from controls synthesized normal amounts of IgG, IgM, and anti-HBc but still did not synthesize detectable amounts of anti-HBs. In the converse experiments, B lymphocytes from controls were co-cultured with irradiated T lymphocytes from carriers. The T lymphocytes from 16 of 24 carriers augmented anti-HBs production by control B cells normally, the remaining eight did not. Finally, mixtures of control B cells and control irradiated T lymphocytes were co-cultured with T lymphocytes from chronic HBsAg carriers. 5 of 12 carriers demonstrated active suppression of anti-HBs production, and in three this suppression was specific, as IgG and IgM production remained normal

  5. Long term effects of radiation of T and B lymphocytes in peripheral blood of patients with Hodgkin's disease

    International Nuclear Information System (INIS)

    Total lymphocyte counts, and the percentage of T and B lymphocytes and monocytes in untreated patients with Hodgkin's disease were not significantly different from those observed in normal donors. At the completion of radiotherapy, the mean total lymphocyte count of 503/mm3 was 4 SD below the mean for normal controls. Although a group of 26 patients in continuous complete remission from 12 to 111 months after radiation treatment regained normal total numbers of lymphocytes and monocytes, they exhibited a striking T lymphocytopenia and B lymphocytosis. Concomitantly, there was a significant increase of null (neither T nor B) lymphocytes. The response of peripheral blood lymphocytes to phytohemagglutinin, concanavalin A, and tetanus toxoid before treatment was significantly impaired. 1 to 10 yr after completion of treatment, there seemed to be little or no recovery of these responses. The capacity of peripheral blood lymphocytes to respond to allo-antigens on foreign lymphocytes in vitro (mixed lymphocyte reaction) was normal in nine untreated patients. However, the mixed lymphocyte reaction was markedly impaired during the first 2 yr after treatment. There was a partial and progressive restoration of the mixed lymphocyte reaction during the next 3 yr, and normal responses were observed in patients in continuous complete remission for 5 yr or more. The in vivo response to dinitrochlorobenzene was also examined. 88 percent (15/17) of patients initially sensitive to dinitrochlorobenzene were anergic to the allergen at the completion of a course of radiotherapy, but nine of these regained their hypersensitivity response during the 1st yr after treatment. The restoration of cell mediated immune functions after radiotherapy is time dependent and its kinetics may differ for various T-cell functions

  6. Ratio of monocytes to lymphocytes in peripheral blood in patients diagnosed with active tuberculosis

    Directory of Open Access Journals (Sweden)

    Jun Wang

    2015-04-01

    Full Text Available Objective:The ratio of monocytes to lymphocytes in peripheral blood could reflect an indi- vidual's immunity to Mycobacterium tuberculosis. The objective of this study was to evaluate the relationship between ratio of monocytes to lymphocytes and clinical status of patients with active tuberculosis.Methods:This was a retrospective review of data collected from the clinical database of The Fifth People's Hospital of Wuxi, Medical College of Jiangnan University. A total of 419 patients who had newly diagnosed active tuberculosis and 108 cases from 419 patients with tuberculosis therapy either near completion or completed were selected. Controls were 327 healthy donors.Results:Median ratio of monocytes to lymphocytes was 0.36 (IQR, 0.22-0.54 in patients before treatment, and 0.16 (IQR, 0.12-0.20 in controls (p25% was significant predictors for active tuberculosis (OR = 114.73, 95% CI, 39.80-330.71; OR = 89.81, 95% CI, 53.18-151.68, respectively. After treatment, the median ratio of monocytes to lymphocytes recovered to be nearly normal. Compared to other patients, patients with extrapulmonary tuberculosis and of age >60 years were more likely to have extreme ratio of monocytes to lymphocytes (AOR = 2.57, 95% CI, 1.08-6.09; AOR = 4.36, 95% CI, 1.43-13.29, respectively.Conclusions:Ratio of monocytes to lymphocytes 25% is predictive of active tuberculosis.

  7. Signal integration during T lymphocyte activation and function: lessons from the Wiskott-Aldrich syndrome

    Directory of Open Access Journals (Sweden)

    Vinícius eCotta-de-Almeida

    2015-02-01

    Full Text Available Over the last decades, research dedicated to the molecular and cellular mechanisms underlying Primary immunodeficiencies (PID has helped to understand the etiology of many of these diseases and to develop novel therapeutic approaches. Beyond these aspects, PID are also studied because they offer invaluable natural genetic tools to dissect the human immune system. In this review, we highlight the research that has focused over the last 20 years on T lymphocytes from Wiskott-Aldrich syndrome (WAS patients. WAS T lymphocytes are defective for the WAS protein (WASP, a regulator of actin cytoskeleton remodeling. Therefore, study of WAS T lymphocytes has helped to grasp that many steps of T lymphocyte activation and function depend on the crosstalk between membrane receptors and the actin cytoskeleton. These steps include motility, immunological synapse assembly, signaling, as well as the implementation of helper, regulatory and cytotoxic effector functions. The recent concept that WASP also works as a regulator of transcription within the nucleus is an illustration of the complexity of signal integration in T lymphocytes. Finally, this review will discuss how further study of WAS may contribute to solve novel challenges of T lymphocyte biology.

  8. Oxidative Damage in Lymphocytes of Copper Smelter Workers Correlated to Higher Levels of Excreted Arsenic

    Science.gov (United States)

    Escobar, Jorge; Varela-Nallar, Lorena; Coddou, Claudio; Nelson, Pablo; Maisey, Kevin; Valdés, Daniel; Aspee, Alexis; Espinosa, Victoria; Rozas, Carlos; Montoya, Margarita; Mandiola, Cristian; Rodríguez, Felipe E.; Acuña-Castillo, Claudio; Escobar, Alejandro; Fernández, Ricardo; Diaz, Hernán; Sandoval, Mario; Imarai, Mónica; Rios, Miguel

    2010-01-01

    Arsenic has been associated with multiple harmful effects at the cellular level. Indirectly these defects could be related to impairment of the integrity of the immune system, in particular in lymphoid population. To characterize the effect of Arsenic on redox status on this population, copper smelter workers and arsenic unexposed donors were recruited for this study. We analyzed urine samples and lymphocyte enriched fractions from donors to determinate arsenic levels and lymphocyte proliferation. Moreover, we studied the presence of oxidative markers MDA, vitamin E and SOD activity in donor plasma. Here we demonstrated that in human beings exposed to high arsenic concentrations, lymphocyte MDA and arsenic urinary levels showed a positive correlation with SOD activity, and a negative correlation with vitamin E serum levels. Strikingly, lymphocytes from the arsenic exposed population respond to a polyclonal stimulator, phytohemaglutinin, with higher rates of thymidine incorporation than lymphocytes of a control population. As well, similar in vitro responses to arsenic were observed using a T cell line. Our results suggest that chronic human exposure to arsenic induces oxidative damage in lymphocytes and could be considered more relevant than evaluation of T cell surveillance. PMID:21253489

  9. NEUROTRANSMITTERS AND IMMUNITY: 1. DOPAMINE

    Directory of Open Access Journals (Sweden)

    Lucian Hritcu

    2007-08-01

    Full Text Available Dopamine is one of the principal neurotransmitters in the central nervous system (CNC, and its neuronal pathways are involved in several key functions such as behavior (Hefco et al., 2003a,b, control of movement, endocrine regulation, immune response (Fiserova et al., 2002; Levite et al., 2001, Hritcu et al., 2006a,b,c, and cardiovascular function. Dopamine has at least five G-protein, coupled receptor subtypes, D1-D5, each arising from a different gene (Sibley et al., 1993. Traditionally, these receptors have been classified into D1-like (the D1 and D5 and D2-like (D2, D3 and D4 receptors subtypes, primarily according to their ability to stimulate or inhibit adenylate cyclase, respectively, and to their pharmacological characteristics (Seeman et al., 1993. Receptors for dopamine (particularly of D2 subclass are the primary therapeutic target in a number of neuropathological disorders including schizophrenia, Parkinson’s disease and Huntington’s chorea (Seeman et al., 1987. Neither dopamine by itself, nor dopaminergic agonists by themselves, has been shown to activate T cell function. Nevertheless, lymphocytes are most probably exposed to dopamine since the primary and secondary lymphoid organs of various mammals are markedly innervated, and contain nerve fibers which stain for tyrosine hydroxylase (Weihe et al., 1991, the enzyme responsible for dopamine synthesis. Moreover, cathecolamines and their metabolites are present in single lymphocytes and in extracts of T and B cell clones, and pharmacological inhibition of tyrosine hydroxylase reduces catecholamine levels, suggesting catecholamine synthesis by lymphocytes (Bergquist et al., 1994. The existence of putative dopamine receptors of D2, D3, D4 and D5 subtypes on immune cells has been proposed of several authors, primarily on the basis of dopaminergic ligand binding assays and specific mRNA expression as monitored by reverse transcription-PCR. Several experiments evoked the idea of a

  10. Lymphocyte migration and radiation lymphopenia

    Energy Technology Data Exchange (ETDEWEB)

    Ekstrand, K.E.; Plunkett, S.; Heise, E.R.; Dixon, R.L.; Raben, M.

    1981-10-01

    The dose received by suppressor and helper T lymphocyte suppopulations during a course of pelvic radiation therapy is calculated, taking into account variances in the migration pattern of the two cell types. It is found that the difference in the calculated dose may explain the apparent paradox that the cell type, which is found to be more radioresistant in vitro, is more depleted by the in vivo irradiation.

  11. Lymphocyte migration and radiation lymphopenia

    International Nuclear Information System (INIS)

    The dose received by suppressor and helper T lymphocyte suppopulations during a course of pelvic radiation therapy is calculated, taking into account variances in the migration pattern of the two cell types. It is found that the difference in the calculated dose may explain the apparent paradox that the cell type, which is found to be more radioresistant in vitro, is more depleted by the in vivo irradiation

  12. Adult Immunization

    OpenAIRE

    Omer Coskun

    2008-01-01

    Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years) require. There are also other vaccines that need to be tailored t...

  13. Forcing it on: Cytoskeletal dynamics during lymphocyte activation

    Science.gov (United States)

    Upadhyaya, Arpita

    2012-02-01

    Formation of the immune synapse during lymphocyte activation involves cell spreading driven by large scale physical rearrangements of the actin cytoskeleton and the cell membrane. Several recent observations suggest that mechanical forces are important for efficient T cell activation. How forces arise from the dynamics of the cytoskeleton and the membrane during contact formation, and their effect on signaling activation is not well understood. We have imaged membrane topography, actin dynamics and the spatiotemporal localization of signaling clusters during the very early stages of spreading. Formation of signaling clusters was closely correlated with the movement and topography of the membrane in contact with the activating surface. Further, we observed membrane waves driven by actin polymerization originating at these signaling clusters. Actin-driven membrane protrusions likely play an important role in force generation at the immune synapse. In order to study cytoskeletal forces during T-cell activation, we studied cell spreading on elastic gels. We found that gel stiffness influences cell morphology, actin dynamics and receptor activation. Efforts to determine the quantitative relationships between cellular forces and signaling are underway. Our results suggest a role for cytoskeleton driven forces during signaling activation in lymphocytes.

  14. [Potency determination of horse anti-human-lymphocyte serum (ALS) by means of the lymphocyte resistance test, a modification of Schroder's leukocyte resistance test].

    Science.gov (United States)

    Mundt, B; Preussner, S; Frick, G; Bast, G

    1975-01-01

    The leukocyte resistance test of Schröder was used for the purpose of modifying the in vitro determination of cytotoxic potency of ALS during the course of immunization. In contrast to the original method, where the test was carried out with whole blood, the incubation was made with pure lymphocyte cell suspensions. The results obtained show that the extensive procedure of examination enables the cytotoxic effectiveness of antilymphocytic antibodies to be evaluated. PMID:54295

  15. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  16. Failure of freshly inplanted alloantigen in vivo to attract circulating allosensitized lymphocytes.

    Science.gov (United States)

    Migliori, R J; Hoffman, R A; Gruber, S A; Debe, E C; Ascher, N L; Simmons, R L

    1988-02-01

    The important role served by donor-specific T lymphocytes in allograft rejection is well accepted. However, the mechanisms that attract the first alloreactive T cells to the graft are unclear. This study was performed to determine whether circulating specifically sensitized lymphocytes are attracted to alloantigen expressed on the surface of donor cells prior to the initiation of inflammatory reactions by the host. 111Indium-oxine labeled, bulk sensitized lymphocytes were injected intravenously into syngeneic mice bearing allogeneic and syngeneic peritoneal exudate cells in opposite hind footpads. Initially, twice as many sensitized lymphocytes were attracted to feet bearing the syngeneic peritoneal cells rather than the allogeneic peritoneal cells. In fact, the activity recovered from the allogeneic peritoneal cell depot was no greater than a contralateral footpad bearing media alone. This selective recruitment was present as early as 30 min following the transfer of radiolabeled cells. Furthermore, the labeled specifically sensitized lymphocytes were attracted to syngeneic macrophages within the peritoneal cell population. No other syngeneic and no allogeneic cells, at all, were capable of attracting circulating sensitized cells. Like specifically sensitized lymphocytes, thymocytes and concanavalin A blasts preferentially homed to sites of syngeneic macrophage deposition. Finally, clones of allospecific cytolytic and helper T cells also failed to migrate to sites of the specified donor alloantigen deposition. Thus, highly immune T cells accumulated, preferentially at sites of syngeneic macrophage inoculation. There is therefore no evidence to support the hypothesis that circulating specifically sensitized lymphocytes are attracted to alloantigen in vivo. Rather, it appears that the initial attraction of specifically sensitized, as well as unsensitized, lymphocytes is directed toward syngeneic macrophages. These data lend support to the hypothesis that the

  17. Iron, folacin, vitamin B12 and zinc status and immune response in the elderly

    International Nuclear Information System (INIS)

    The relationships of iron, folacin, vitamin B12 and zinc status to cell-mediated immune response were investigated among 125 healthy, elderly persons (60-87 years of age). Plasma ferritin, plasma and red cell folate, and plasma vitamin B12 levels were assayed immuno-radiometrically. Plasma and hair zinc levels were determined by atomic absorption spectroscopy. Immune response was determined by transformation of peripheral blood lymphocytes after stimulation with phytohemagglutinin (PHA) and concanavalin A (con A), and in mixed lymphocyte reaction. Deficiencies of iron, folacin vitamin B12 and zinc were each associated (independently) with significantly lower lymphocyte responses to PHA and con A, and mixed lymphocyte reaction (P 12 or zinc. Further, they suggest that deficiencies of these nutrients may play a role in the depression of cell-mediated immunity with age, which in turn may lead to increased susceptibility to infectious diseases and cancer in the elderly

  18. Role of cellular immunity in halothane hepatitis: an in vitro study

    Institute of Scientific and Technical Information of China (English)

    Lu Zhijie; Miao Xuerong; Wang Xiaoyan; Wu Jingxiang; Lv Xin; Yu Weifeng

    2008-01-01

    Objective: To explore the effect of cellular immunity in halothane hepatitis. Methods: Hepatotoxicity model was established by exposing male Hartley guinea pigs to 1% halothane via inspiration for 4 h each time for 1 or 3 times within a 42-day interval. Then their hepatocytes and lymphocytes were collected and divided into 2 parts for different cultures. Hepatocytes were cultivated with or without 1% halothane for 4 h and lymphocytes were cultivated with or without 12.5 μg/ml trifluoroacetylated guinea pig serum albumin (TFA-GSA). Then the 2 kinds of hepatocytes were co-cultivated with lymphocytes (1:100) with or without TFA-GSA induction respectively and the supernatant fluid was taken after 24, 48 and 72 h to determine the concentration of alanine aminotransferase (ALT). The halothane cultivated hepatocytes were co-cultivated with various proportion of TFA-GSA antigen induced lymphocytes and ALT was determined after 48 h to determine the proper proportion of hepatocytes and lymphocyte. Results: Lymphocytes of 3 times halothane induced guinea pigs caused a significant increase of ALT in hepatocytes with or without halothane induction. But the lymphocytes of l time halothane induced guinea pigs only caused a significant increase of ALT in hepatocytes with induction of halothane. The increase of ALT was only seen after 48- and 72-hour co-culture. The proper proportion of hepatocytes and lymphocytes was l:100 for lymphocytes cytotoxicity. Conclusion: Lymphocytes is sensitized after inhalation of halothane and generates cytotoxicity to hepatocytes. The immune response of lymphocytes to hepatocytes will be enhanced by repeated inhalation of halothane. The cellular immunity may be one of the mechanisms of halothane induced hepatotoxicity.

  19. T-lymphocyte dependency of B-lymphocyte blastogenic response to phytomitogens

    International Nuclear Information System (INIS)

    Human peripheral blood T and B lymphocytes were separated by a method based on the stable rosette formation of T lymphocytes with neuraminidase-treated sheep erythrocytes, followed by centrifugation over a Ficoll-Hypaque gradient. Monocytes were isolated from the T-depleted B lymphocyte preparation by allowing the monocytes to ingest iron particles and by subsequent centrifugation over a Ficoll-Hypaque gradient. The T lymphocytes responded extremely well to PHA and very well to PWM, while the B lymphocytes were unresponsive to either PHA or PWM. However, when the B lymphocytes were cultured together with irradiated autologous or allogeneic T lymphocytes (1 : 1,1:2 or 1 : 4 ratio), both PHA and PWM became mitogenic to B lymphocytes. Irradiated T lymphocytes alone did not respond to either PHA or PWM, indicating that the 3H-thymidine incorporation seen in the mixed-cell culture was due to the activation of unirradiated B lymphocytes. The B lymphocytes failed to respond to these phytomitogens in the presence of lower concentrations of irradiated T lymphocytes. The monocytes were found to be incapable of helping the B lymphocytes to respond to PHA or PWM. (author)

  20. In vitro modeling of the interaction between human epithelial cells and lymphocytes upon influenza infection.

    Science.gov (United States)

    Ilyushina, Natalia A; Wright, Peter F

    2016-09-01

    Influenza viruses are a continuous threat to humans because of their ability to cross species barriers and adapt to new hosts. Data from murine studies, along with limited human data, suggest that CD8(+) cytotoxic T lymphocytes (CTL) that recognize conserved epitopes of structural influenza proteins are the main mediators of influenza virus clearance. Additionally, the fact that many CTLs recognize epitopes shared between different influenza strains offers the potential for broad cross-strain immunity. However, the mechanisms of cellular immunity against influenza viruses are poorly defined in humans, where the CTL response has been hard to measure and interpret. We developed a novel CTL assay that utilizes fully differentiated nasal human epithelial cells taken from volunteers as permissive targets for autologous peripheral blood-derived influenza virus-specific cytotoxic T lymphocytes. This in vitro system of human lymphocyte-epithelial cell co-cultures can be considered as the closest approximation to events in vivo and can be employed for studying the interactions between the pathogen and human host. Modeling of the natural interaction process between the primary cell type that supports the productive replication of influenza and immune cells may allow us to put in perspective CTLs as a correlate of immunity to influenza in humans. PMID:27102577

  1. Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    Science.gov (United States)

    2016-08-31

    Anemia; Fever, Sweat, and Hot Flashes; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; Weight Change

  2. Persistent hyperglycemia modulates gut immune function and microbiota in rats

    OpenAIRE

    Mori, Katsuya; Suzuki, Takeshi; Igarashi, Toru; Inoue, Kei; Asahara, Takashi; Nomoto, Koji; Seki, Hiroyuki; Yamada, Takashige; Minamishima, Shizuka; Kosugi, Shizuko; Katori, Nobuyuki; Morisaki, Hiroshi

    2015-01-01

    Background Since hyperglycemia-induced cellular dysfunction could be associated with alterations of the immune system, we tested the hypothesis that hyperglycemia augments the aberrant immune responses such as inflammation and differentiation of CD4+ T lymphocytes in the mesenteric lymph nodes (MLNs), and induces alterations of microbiota both under physiological and pathological conditions. Methods Male Wistar rats were randomly allocated into 4 groups: Control and Endotoxemia (lipopolysacch...

  3. Lymphocyte migration into syngeneic implanted lymph nodes

    International Nuclear Information System (INIS)

    To judge the functional activity of lymphocytes of an implanted lymph node (LN), the proliferative response of lymphocytes of the implanted organ in the blast-transformation reaction in vitro and their ability to induce a local graft versus host reaction (GVHR) were determined. The lymphocyte suspension for labeling with 51Cr was obtained from peripheral LN in different situations from syngeneic mice. The resulting lymphocyte suspension was labeled with a solution of sodium chromate-51Cr in a concentration of 20-40 microCi/100.106 cells in 1 ml for 40 min at 370C. The proliferative activity of a suspension of lymphocytes was estimated as incorporation of 3H-thymidine into DNA during incubation of the cell suspension for 3 days. Data on migration of 51Cr-labeled cells and the results of the morphological observations revealed marked ability of lymphocytes of the peripheral pool to colonize the regenerating stroma

  4. Human lymphocyte production of immunoreactive thyrotropin.

    OpenAIRE

    Smith, E M; Phan, M.; Kruger, T E; Coppenhaver, D H; Blalock, J E

    1983-01-01

    Interferon-alpha inducers were previously shown to cause human lymphocyte production of a corticotropin (ACTH)-like peptide. Thyrotropin (TSH) was not produced under these conditions. In contrast, this report shows that a T-cell mitogen (staphylococcal enterotoxin A), which does not induce the ACTH-like peptide, caused human lymphocyte production of an immunoreactive (ir) TSH. Lymphocyte synthesis of the ir TSH was first detectable at 24 hr, peaked at 48 hr, and thereafter declined. NaDodSO4/...

  5. Lymphocytic Thrombophilic Arteritis Induced by Minocycline

    OpenAIRE

    Kassardjian, Michael; Horowitz, David; Shitabata, Paul K.; Clark, Lani E.

    2012-01-01

    Lymphocytic thrombophilic arteritis is an entity only recently defined in the literature. This term describes a distinctive histopathological combination of lymphocytic vascular inflammation associated with a hyalinized fibrin ring in the vessel lumina, changes reflecting a thrombophilic endovasculitis. The authors present the case of a woman who developed lymphocytic thrombophilic arteritis coinciding with the use of minocycline. In addition to these histopathological findings, the cutaneous...

  6. Splenic lymphoma with circulating villous lymphocytes.

    OpenAIRE

    Imbing, F; Kumar, D.; Kumar, S.; Yuoh, G; Gardner, F

    1995-01-01

    This report describes the occurrence of splenic lymphoma with villous lymphocytes (SLVL) in a 56 year old white female with a family history of chronic lymphocytic leukaemia. Other unusual features included a marked lymphocytosis with counts up to 224 x 10(9)/l and marked clumping of lymphocytes in EDTA anticoagulated blood. The neoplastic cells were CD19+, CD20+, CD22+, CD22+, IgM+, lambda+, kappa-, CD5-, and CD10-. The spleen had nodular infiltrates of B lymphocytes in the region of the whi...

  7. Effects of irradiation on normal human lymphocytes

    International Nuclear Information System (INIS)

    After the normal human blood was exposured to 60Co gamma-rays, neutrons and X-ray with different doses, the human lymphocytes induced by PHA, ConA, LPS and PWM were cultured in vitro. The proliferation and differentiation kinetics of human lymphocytes were studied by using 3H-TdR, 14C-UR and 14C-valine incorporation technique. The irradiation inhibition on syntheses of DNA, RNA and protein was observed. The results from the experiments showed: (1) The proliferation and differentiation of human lymphocytes, different lymphocytes subgroups, induced by various mitogens were different. (2) The injury effects of irradiation on synthese of DNA and protein in the lymphocytes stimulated with ConA and PHA were greater than that in the lymphocytes induced by LPS and PWM. (3) The injury effect of lymphocytes irradiated by neutrons was greater than that lymphocytes irradiated by gamma-rays and X-rays. (4) In the irradiated human lymphocytes subgroups induced by various mitogens, the more ability of repairing broken DNA strand subgroup had, the more strong resistance to irradiation it was

  8. Elicitation of Simian Immunodeficiency Virus-Specific Cytotoxic T Lymphocytes in Mucosal Compartments of Rhesus Monkeys by Systemic Vaccination

    OpenAIRE

    Baig, Jamal; Levy, Daniel B.; McKay, Paul F.; Schmitz, Joern E.; Santra, Sampa; Subbramanian, Ramu A.; Kuroda, Marcelo J.; Lifton, Michelle A.; Gorgone, Darci A.; Wyatt, Linda S.; Moss, Bernard; Huang, Yue; Chakrabarti, Bimal K.; Ling XU; Kong, Wing-Pui

    2002-01-01

    Since most human immunodeficiency virus (HIV) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an HIV infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. Studying vaccine-elicited mucosal immune responses has been problematic because of the difficulties associated with sampling T lymphocytes from those anatomic compartments. In the present study, we demonstrate that mucosal cytotoxic T lymph...

  9. Chronic lymphocytic leukaemia: contemporary conceptions of etiology, pathogenesis and peculiarities of clinical manifestations (review

    Directory of Open Access Journals (Sweden)

    Chesnokova N.P.

    2011-06-01

    Full Text Available The research work presents an analysis of literature review and results of investigations on the problems of etiology, pathogenesis, classification and peculiarities of clinical manifestations of chronic lymphocytic leukaemia. Special attention is paid to both contemporary conceptions of carcinogenesis, reflecting the role of proto-oncogenes activation, an-tioncogenes and apoptosis genes suppression in mechanisms of neoplasia development and «specific mechanisms» of oncogenic transformation induction of B-lymphocytes and the subsequent development of the stages of promotion, progression and marked clinical manifestations of formation. Possibility of further improvement of use of immune phe-notype character and oncomarkers in diagnostics of chronic lymphocytic leukaemia clinical variants and in evaluation of effectiveness of its therapy has been indicated in the article

  10. Energy metabolism in developing chicken lymphocytes is altered during the embryonic to posthatch transition.

    Science.gov (United States)

    Rudrappa, Shashidhara G; Humphrey, Brooke D

    2007-02-01

    Adequate energy status in lymphocytes is vital for their development. The ability of developing chicken lymphocytes to acquire and metabolize energy substrates was determined during embryonic days (e) and neonatal days (d) of life when primary-energy substrate metabolism is altered at the whole-animal level. In 3 experiments, bursacytes and thymocytes were isolated on e17, e20, d1, d3, d7, or d14 to analyze markers associated with glucose, glutamine, and lipid metabolism. Bursacyte glucose transporter-3 (Glut-3) mRNA abundance increased from d1 to d14 and hexokinase-1 (HK-1) mRNA abundance was maximum on e20 (Pglutamine metabolism. Understanding the factors that regulate lymphocyte development in neonatal chicks may help promote their adaptive immune responses to pathogens in early life. PMID:17237322

  11. Two-Photon Imaging of Lymphocyte Motility and Antigen Response in Intact Lymph Node

    Science.gov (United States)

    Miller, Mark J.; Wei, Sindy H.; Parker, Ian; Cahalan, Michael D.

    2002-06-01

    Lymphocyte motility is vital for trafficking within lymphoid organs and for initiating contact with antigen-presenting cells. Visualization of these processes has previously been limited to in vitro systems. We describe the use of two-photon laser microscopy to image the dynamic behavior of individual living lymphocytes deep within intact lymph nodes. In their native environment, T cells achieved peak velocities of more than 25 micrometers per minute, displaying a motility coefficient that is five to six times that of B cells. Antigenic challenge changed T cell trajectories from random walks to ``swarms'' and stable clusters. Real-time two-photon imaging reveals lymphocyte behaviors that are fundamental to the initiation of the immune response.

  12. Role of Sphingosine 1-Phosphate Receptor Type 1 in Lymphocyte Egress from Secondary Lymphoid Tissues and Thymus

    Institute of Scientific and Technical Information of China (English)

    Kenji Chiba; Hirofumi Matsuyuki; Yasuhiro Maeda; Kunio Sugahara

    2006-01-01

    Circulation of mature lymphocytes between blood and secondary lymphoid tissues plays a central role in the immune system. Homing of lymphocytes from blood into secondary lymphoid tissues beyond high endothelial venules is highly dependent on the interaction between the chemokines CCL19, CCL21, CXCL12, and CXCL13,and their receptors CCR7, CXCR4 and CXCR5. However, the molecular mechanism(s) of lymphocyte egress from secondary lymphoid tissues to lymph remained unclear. We have found a new class of immunomodulator, FTY720 by chemical modification of vegetative wasp-derived natural product, ISP-I (myriocin). FTY720 has been shown to be highly effective in experimental allograft and autoimmune disease models. A striking feature of FTY720 is the induction of a marked decrease in peripheral blood lymphocytes at doses that show immunomodulating activity in these models. The reduction of circulating lymphocytes by FTY720 is caused by sequestration of iymphocytes into secondary lymphoid tissues and thymus. FTY720 is rapidly converted to (S)-enantiomer of FTY720-phosphate[(S)-FTY720-P] by sphingosine kinase 2 in vivo. (S)-FTY720-P acting as a potent agonist of S1P receptor type 1(S1P1), induces long-term down-regulation of S1P1 on lymphocytes, and thereby inhibits the migration of lymphocytes toward S1P. Thus, it is presumed that FTY720-induced lymphocyte sequestration is due to the inhibition of S1P/S1P1-dependent lymphocyte egress from secondary lymphoid tissues and thymus by its active metabolite (S)-FTY720-P. Throughout the analysis of the mechanism of action of FTY720, it is clarified that S1P/S1P1 interaction plays an important role for lymphocyte egress from secondary lymphoid tissues and thymus.

  13. Effects of alcohol consumption on the allergen-specific immune response in mice

    DEFF Research Database (Denmark)

    Linneberg, Allan; Roursgaard, Martin; Hersoug, Lars-Georg;

    2008-01-01

    There is evidence that chronic alcohol consumption impairs the T-helper 1 (Th1) lymphocyte-regulated cell-mediated immune response possibly favoring a Th2 deviation of the immune response. Moreover, a few epidemiological studies have linked alcohol consumption to allergen-specific IgE sensitization....

  14. Immune thrombocytopenia.

    Science.gov (United States)

    Kistangari, Gaurav; McCrae, Keith R

    2013-06-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary or a secondary form. ITP may affect individuals of all ages, with peaks during childhood and in the elderly, in whom the age-specific incidence of ITP is greatest. Bleeding is the most common clinical manifestation of ITP. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Corticosteroids remain the most common first line therapy for ITP. This article summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. PMID:23714309

  15. Biomarkers of CD4+ CTL cell Mediated Immunity to Tuberculosis

    Science.gov (United States)

    The immune responses mediated by interactions between T-lymphocyte subsets and mycobacteria-infected macrophages are critical for control of tuberculosis. In these studies, the bovine model was used to characterize the cytolytic and mycobactericidal CD4+ T cell response induced by BCG vaccination. ...

  16. 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.

  17. The influence of leptin on the activity of lung lymphocytes under simulated microgravity.

    Science.gov (United States)

    Li, Xu; Liu, Chang-Ting; Zhou, Hong

    2009-10-01

    Exposure to microgravity has been implicated in the compromised immune function in space travellers, resulting in opportunistic infections, poor wound healing, and cancer. Since recent studies have suggested that leptin was capable of modulating immune responses, the purpose of this study was to examine effects of microgravity on the activation and proliferation of rat lung lymphocytes and then to examine the effects of leptin-mediated signal transduction mechanisms of lymphocyte activation in these same conditions. In control conditions (T-flasks cultured cells) leptin was not able by itself to increase lymphocytes proliferation, or induce significant increase of either IL-2 production or expression of lymphocytes activation markers, such as CD25 and CD71, while it markedly enhanced the positive effects induced on these parameters by concanavalin A (ConA). Using clinostatic rotating wall vessel (RWV) bioreactors to simulate a microgravity environment, we found that ConA responsiveness was inhibited. Moreover, under these conditions, leptin was not able to reverse these impaired functions. Accordingly with the above cited inhibitory effects exerted by the simulated microgravity environment, evidence was also obtained of defects in lymphocyte intracellular signal transduction induced by the incubation in RWV bioreactors, namely concerning decreased ConA-mediated PKC activity, and reduced expression of NF-kappaB, c-fos, and ERK1/2. Again, leptin appeared to be unable in restoring a physiologic increase of these parameters, different from what could be observed after complementation of the ConA-mediated signalling with phorbol myristate acetate, which instead demonstrated to overcome the inhibition of lymphocytes activating functions, in the presence of simulated microgravity conditions. PMID:19626337

  18. Immunophenotyping of peripheral blood lymphocytes at children and adolescents with Hashimoto's thyroiditis

    International Nuclear Information System (INIS)

    Two-color immunophenotyping of lymphocyte subsets using a lysed whole blood method was performed in 46 children and adolescents with Hashimoto's thyroiditis (HT) from contaminated areas and in 18 children from 'clean' areas of Belarus. 46 healthy children of matched age and sex distribution were used as control group. Analysis of lymphocyte subsets in children with HT living in contamination areas shower a considerable decrease in the levels of total lymphocytes, CD8+ T cells (T-suppressors), total B cells, and CD5+ B cells together with an activation of NK and CD56+, CD8+CD57+T cells (T-killers not restricted by HLA antigens). The study of cellular immunity in children with different doses of ionizing radionuclides revealed that prolonged influence of very small doses of ionizing radiation resulted in significant changes in lymphocyte subsets; interestingly, B cell subsets were the first to react to such influence while stability of T-killers and NK was the highest. These changes were the greatest in children with HT with the highest dose of incorporated radionuclides. Significant correlation between the levels of main lymphocyte subsets and the doses of accumulated radionuclides observed in this study also indicated that their relation was dose-dependent. The results of the study suggest that 1) lymphocyte subsets are different in their reaction to chronic internal irradiation which, evidently, is determined by their proliferation activity, degree of differentiation, and function; 2) increase in the dose of incorporated radionuclides in children and adolescents with HT leads to different reaction of sells- a decrease in T-suppressors, B cells and activation of cells responsible for nonspecific cytotoxicity- T-killers unrestricted by HLA antigens and NK; 3) children and adolescents with HT from contaminated regions have much more pronounced imbalance of cellular immunity and activation of cellular cytotoxic reactions damaging the thyroid tissue than those with HT

  19. STUDIES OF LYMPHOCYTE SUBSETS IN PATIENTS WITH A MIXED INFECTION CAUSED BY THE VIRUSES FROM HERPESVIRIDAE FAMILY

    Directory of Open Access Journals (Sweden)

    T. I. Dolgikh

    2010-01-01

    Full Text Available Present work deals with specific immunologic changes that are typical to various types of mixed infection caused by viruses from Herpesviridae family during their activation phase. These changes include increased amounts of CD3+/CD25+ lymphocytes and CD3+/CD4+ cells, decreased levels of CD3+/CD95+ cells, increased contents of natural killer cells, altered interrelations between the immune system parameters. Involvement of cytomegalovirus or Epstein-Barr virus (EBV in the mixed infection is associated with some special changes of the lymphocyte subsets. I.e., a co-infection with herpes virus simplex (HSV type 1/2 and cytomegalovirus is characterized by increased amounts of activated T-lymphocytes and T-helper cells, whereas mixed HSV/EBV infection is accompanied by sharp reduction in CD3+/CD95+ lymphocytes.

  20. Stochastic model for computer simulation of the number of cancer cells and lymphocytes in homogeneous sections of cancer tumors

    CERN Document Server

    Castellanos-Moreno, Arnulfo; Corella-Madueño, Adalberto; Gutiérrez-López, Sergio; Rosas-Burgos, Rodrigo

    2014-01-01

    We deal with a small enough tumor section to consider it homogeneous, such that populations of lymphocytes and cancer cells are independent of spatial coordinates. A stochastic model based in one step processes is developed to take into account natural birth and death rates. Other rates are also introduced to consider medical treatment: natural birth rate of lymphocytes and cancer cells; induced death rate of cancer cells due to self-competition, and other ones caused by the activated lymphocytes acting on cancer cells. Additionally, a death rate of cancer cells due to induced apoptosis is considered. Weakness due to the advance of sickness is considered by introducing a lymphocytes death rate proportional to proliferation of cancer cells. Simulation is developed considering different combinations of the parameters and its values, so that several strategies are taken into account to study the effect of anti-angiogenic drugs as well the self-competition between cancer cells. Immune response, with the presence ...

  1. Persisting injuries in immune system and their effects on health in a-bomb survivors

    International Nuclear Information System (INIS)

    This review describes findings concerning persisting effects of A-bomb radiation on immune cells and their relation to diseases. Injuries in immune system are mainly the depression of cellular immunity mediated by T-lymphocytes, especially CD4 T-cells, and the elevation of humoral immunity by B-cells. These are conceivably the imbalance results in immune system of incomplete recovery of those T-cells after exposure and thymus retraction by aging and of consequently affecting the functional differentiation of CD4 T-cells to lower the cellular immunity and to elevate the humoral immunity. Lowered cellular immunity in the survivors can be related to their liver and cardiovascular diseases caused by infection and cancer caused by tumor antigens and oncoviruses. Thus immunological investigations of the survivors are revealing not only the effect of radiation on the immune system but also the correlation between immunity and diseases. (K.H.)

  2. Membrane characteristics and functional analysis of human T and B lymphocytes : a contributions to the analysis of immunodeficiency in children

    NARCIS (Netherlands)

    R.K.B. Schuurman

    1980-01-01

    textabstractConcepts of the immune system in man change along with models based on experimental research (52). In the past three decennia the function of human lymphocytes~ their differentiation pathways and their disorders have been unraveled by a close collaboration between animal and human immuno

  3. Peripheral CD25 positive T lymphocytes with biased T cell receptor Vβ gene usage in autoimmune endogenous posterior uveitis

    OpenAIRE

    Tighe, P J; Forrester, J V; Liversidge, J.; Sewell, H F

    1995-01-01

    Aims—To determine T cell receptor (TCR) Vβ gene usage in peripheral blood T lymphocytes of patients with endogenous posterior uveitis (EPU). If biased TCR variable (V) gene usage occurs in this autoimmune disease, it should be detectable in immune activated peripheral blood T cells in vivo.

  4. Variable Lymphocyte Receptor Recognition of the Immunodominant Glycoprotein of Bacillus anthracis Spores

    Energy Technology Data Exchange (ETDEWEB)

    Kirchdoerfer, Robert N.; Herrin, Brantley R.; Han, Byung Woo; Turnbough, Jr., Charles L.; Cooper, Max D.; Wilson, Ian A. (SNU); (Scripps); (Emory); (UAB); (Emory Vaccine)

    2012-07-25

    Variable lymphocyte receptors (VLRs) are the adaptive immune receptors of jawless fish, which evolved adaptive immunity independent of other vertebrates. In lieu of the immunoglobulin fold-based T and B cell receptors, lymphocyte-like cells of jawless fish express VLRs (VLRA, VLRB, or VLRC) composed of leucine-rich repeats and are similar to toll-like receptors (TLRs) in structure, but antibodies (VLRB) and T cell receptors (VLRA and VLRC) in function. Here, we present the structural and biochemical characterization of VLR4, a VLRB, in complex with BclA, the immunodominant glycoprotein of Bacillus anthracis spores. Using a combination of crystallography, mutagenesis, and binding studies, we delineate the mode of antigen recognition and binding between VLR4 and BclA, examine commonalities in VLRB recognition of antigens, and demonstrate the potential of VLR4 as a diagnostic tool for the identification of B. anthracis spores.

  5. Neospora caninum-infected cattle develop parasite-specific CD4+ cytotoxic T lymphocytes.

    Science.gov (United States)

    Staska, Lauren M; McGuire, Travis C; Davies, Christopher J; Lewin, Harris A; Baszler, Timothy V

    2003-06-01

    Cattle infected with Neospora caninum readily experience transplacental parasite transmission, presumably after maternal parasitemia, leading to abortion or birth of congenitally infected calves. Cytotoxic T lymphocytes (CTL) are important mediators of protective immunity against Toxoplasma gondii, an intracellular apicomplexan protozoan closely related to N. caninum. In this study, N. caninum-specific CTL expanded from peripheral blood mononuclear cells of two major histocompatibility complex-mismatched, experimentally infected cattle were identified by using a (51)Cr release cytotoxicity assay. Enrichment and blocking of CD4(+)- and CD8(+)-T-lymphocyte effector subsets indicated that CD4(+) CTL killed N. caninum-infected, autologous target cells and that killing was mediated through a perforin/granzyme pathway. Detection and characterization of CTL responses to N. caninum in the natural, outbred, bovine host will facilitate identification of immunogens and design of immunization strategies to induce parasite-specific CTL against transplacental N. caninum transmission in cattle. PMID:12761108

  6. The Bidirectional Relationship between Sleep and Immunity against Infections

    Directory of Open Access Journals (Sweden)

    Elizabeth G. Ibarra-Coronado

    2015-01-01

    Full Text Available Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The function of sleep in altering immune responses must be determined to understand how sleep deprivation increases the susceptibility to viral, bacterial, and parasitic infections. There are several explanations for greater susceptibility to infections after reduced sleep, such as impaired mitogenic proliferation of lymphocytes, decreased HLA-DR expression, the upregulation of CD14+, and variations in CD4+ and CD8+ T lymphocytes, which have been observed during partial sleep deprivation. Also, steroid hormones, in addition to regulating sexual behavior, influence sleep. Thus, we hypothesize that sleep and the immune-endocrine system have a bidirectional relationship in governing various physiological processes, including immunity to infections. This review discusses the evidence on the bidirectional effects of the immune response against viral, bacterial, and parasitic infections on sleep patterns and how the lack of sleep affects the immune response against such agents. Because sleep is essential in the maintenance of homeostasis, these situations must be adapted to elicit changes in sleep patterns and other physiological parameters during the immune response to infections to which the organism is continuously exposed.

  7. Sympathetic neural modulation of the immune system

    International Nuclear Information System (INIS)

    One route by which the central nervous system communicates with lymphoid organs in the periphery is through the sympathetic nervous system (SNS). To study SNS regulation of immune activity in vivo, selective removal of peripheral noradrenergic nerve fibers was achieved by administration of the neurotoxic drug, 6-hydroxydopamine (6-OHDA), to adult mice. To assess SNS influence on lymphocyte proliferation in vitro, uptake of 125iododeoxyuridine (125IUdR), a DNA precursor, was measured following 6-OHDA treatment. Sympathectomy prior to epicutaneous immunization with TNCB did not alter draining lymph nodes (LN) cell proliferation, whereas 6-OHDA treatment before footpad immunization with KLH reduced DNA synthesis in popliteal LN by 50%. In mice which were not deliberately immunized, sympathectomy stimulated 125IUdR uptake inguinal and axillary LN, spleen, and bone marrow. In vitro, these LN and spleen cells exhibited decreased proliferation responses to the T cell mitogen, concanavalin A (Con A), whereas lipopolysaccharide (LPS)-stimulated IgG secretion was enhanced. Studies examining 51Cr-labeled lymphocyte trafficking to LN suggested that altered cell migration may play a part in sympathectomy-induced changes in LN cell function

  8. Lipopolysaccharide Increases Immune Activation and Alters T Cell Homeostasis in SHIVB’WHU Chronically Infected Chinese Rhesus Macaque

    OpenAIRE

    Zhang, Gao-Hong; Wu, Run-Dong; Zheng, Hong-Yi; Zhang, Xiao-Liang; Zhang, Ming-Xu; Tian, Ren-Rong; Liu, Guang-Ming; Pang, Wei; Zheng, Yong-Tang

    2015-01-01

    Immune activation plays a significant role in the disease progression of HIV. Microbial products, especially bacterial lipopolysaccharide (LPS), contribute to immune activation. Increasing evidence indicates that T lymphocyte homeostasis disruptions are associated with immune activation. However, the mechanism by which LPS affects disruption of immune response is still not fully understood. Chronically SHIVB'WHU-infected Chinese rhesus macaques received 50 μg/kg body weight LPS in this study....

  9. Lipopolysaccharide Increases Immune Activation and Alters T Cell Homeostasis in SHIVB'WHU Chronically Infected Chinese Rhesus Macaque

    OpenAIRE

    Gao-Hong Zhang; Run-Dong Wu; Hong-Yi Zheng; Xiao-Liang Zhang; Ming-Xu Zhang; Ren-Rong Tian; Guang-Ming Liu; Wei Pang; Yong-Tang Zheng

    2015-01-01

    Immune activation plays a significant role in the disease progression of HIV. Microbial products, especially bacterial lipopolysaccharide (LPS), contribute to immune activation. Increasing evidence indicates that T lymphocyte homeostasis disruptions are associated with immune activation. However, the mechanism by which LPS affects disruption of immune response is still not fully understood. Chronically SHIVB’WHU-infected Chinese rhesus macaques received 50 μg/kg body weight LPS in this study....

  10. Giardia induces proliferation and interferon γ production by intestinal lymphocytes

    OpenAIRE

    Ebert, E

    1999-01-01

    BACKGROUND—Murine intraepithelial lymphocytes kill Giardia lambia; responses of human intestinal lymphocytes to this parasite are unknown. 
AIMS—To examine giardia induced proliferation, interferon γ production, migration, and cytotoxicity by lymphocytes from the human intestine and peripheral blood. 
METHODS—Giardia were added to intraepithelial lymphocytes, lamina propria lymphocytes, and peripheral blood lymphocytes, obtained from jejunal mucosa and blood of otherwise ...

  11. Circulating lymphocyte is an important determinant of the effectiveness of preoperative radiotherapy in advanced rectal cancer

    International Nuclear Information System (INIS)

    Although preoperative radiotherapy (RT) is widely used as the initial treatment for locally advanced rectal cancer (RC) in the neoadjuvant setting, factors determining clinical response have not been adequately defined. In order to find other factors possibly related with radiosensitivity, we evaluated the relationships between circulating blood cell counts and RT effects. In 179 cases with advanced RC, we retrospectively examined hemoglobin (Hb) levels and counts of white blood cells (WBC), platelets and WBC subsets before and after RT and investigated their associations with the complete response (CR) rate together with other clinicopathological factors. The ratio of lymphocytes in WBC taken before RT was significantly greater in 15 CR cases as compared with those in non-CR cases. Patients with high lymphocyte percentages (25.7%) showed better outcome than the counterparts. Conversely, the ratio of neutrophiles was reduced in CR cases. The lymphocyte ratio showed an independent association with CR with multivariate analysis, and tended to be maintained at relatively high levels in CR cases. In RC patients, peripheral blood lymphocytes have a significant impact on the CR rate in response to RT. Lymphocyte-mediated immune reactions are supposed to have positive roles on clinical response in radiotherapy for RC

  12. Cognitive awareness of carbohydrate intake does not alter exercise-induced lymphocyte apoptosis

    Directory of Open Access Journals (Sweden)

    James Wilfred Navalta

    2011-01-01

    Full Text Available OBJECTIVE: The purpose of this investigation was to determine whether cognitive awareness of carbohydrate beverage consumption affects exercise-induced lymphocyte apoptosis, independent of actual carbohydrate intake. INTRODUCTION: Carbohydrate supplementation during aerobic exercise generally protects against the immunosuppressive effects of exercise. It is not currently known whether carbohydrate consumption or simply the knowledge of carbohydrate consumption also has that effect. METHODS: Endurance trained male and female (N = 10 athletes were randomly assigned to one of two groups based on either a correct or incorrect cognitive awareness of carbohydrate intake. In the incorrect group, the subjects were informed that they were receiving the carbohydrate beverage but actually received the placebo beverage. Participants completed a 60-min ride on a cycle ergometer at 80% VO2peak under carbohydrate and placebo supplemented conditions. Venous blood samples were collected at rest and immediately after exercise and were used to determine the plasma glucose concentration, lymphocyte count, and extent of lymphocyte apoptosis. Cognitive awareness, either correct or incorrect, did not have an effect on any of the measured variables. RESULTS: Carbohydrate supplementation during exercise did not have an effect on lymphocyte count or apoptotic index. Independent of drink type, exercise resulted in significant lymphocytosis and lymphocyte apoptosis (apoptotic index at rest = 6.3 ± 3% and apoptotic index following exercise = 11.6 ± 3%, P<0.01. CONCLUSION: Neither carbohydrate nor placebo supplementation altered the typical lymphocyte apoptotic response following exercise. While carbohydrate supplementation generally has an immune-boosting effect during exercise, it appears that this influence does not extend to the mechanisms that govern exercise-induced lymphocyte cell death.

  13. Sleep disruption and its effect on lymphocyte redeployment following an acute bout of exercise.

    Science.gov (United States)

    Ingram, Lesley A; Simpson, Richard J; Malone, Eva; Florida-James, Geraint D

    2015-07-01

    Sleep disruption and deprivation are common in contemporary society and have been linked with poor health, decreased job performance and increased life-stress. The rapid redeployment of lymphocytes between the blood and tissues is an archetypal feature of the acute stress response, but it is not known if short-term perturbations in sleep architecture affect lymphocyte redeployment. We examined the effects of a disrupted night sleep on the exercise-induced redeployment of lymphocytes and their subtypes. 10 healthy male cyclists performed 1h of cycling at a fixed power output on an indoor cycle ergometer, following a night of undisrupted sleep (US) or a night of disrupted sleep (DS). Blood was collected before, immediately after and 1h after exercise completion. Lymphocytes and their subtypes were enumerated using direct immunofluorescence assays and 4-colour flow cytometry. DS was associated with elevated concentrations of total lymphocytes and CD3(-)/CD56(+) NK-cells. Although not affecting baseline levels, DS augmented the exercise-induced redeployment of CD8(+) T-cells, with the naïve/early differentiated subtypes (KLRG1(-)/CD45RA(+)) being affected most. While the mobilisation of cytotoxic lymphocyte subsets (NK cells, CD8(+) T-cells γδ T-cells), tended to be larger in response to exercise following DS, their enhanced egress at 1h post-exercise was more marked. This occurred despite similar serum cortisol and catecholamine levels between the US and DS trials. NK-cells redeployed with exercise after DS retained their expression of perforin and Granzyme-B indicating that DS did not affect NK-cell 'arming'. Our findings indicate that short-term changes in sleep architecture may 'prime' the immune system and cause minor enhancements in lymphocyte trafficking in response to acute dynamic exercise. PMID:25582807

  14. Pregnancy: an immune challenge

    Directory of Open Access Journals (Sweden)

    Maria Angelica Ehara Watanabe

    2014-12-01

    Full Text Available Several studies demonstrate the importance of immunological aspects of pregnancy. During pregnancy, the embryo is implanted in the womb, where it will develop until the end of pregnancy. Amongst the immune aspects, the importance of the modulation of T lymphocytes, natural killers (NK cells and many cytokines in maternal organism can be mentioned. The maternal tolerance to the fetus appears to be mediated by specific maternal hormones and by the expression of human leukocyte antigen G (HLA-G - characteristic in pregnancy. Other studies suggest that fetal rejection and complications during pregnancy may occur because of the presence of minor histocompatibility antigens (mHAg, acquired by blood sharing of the mother with the fetus, and because of the presence of maternal antibodies against the sperm and against the fetus. The purpose of this review is to describe the immunological aspects that allow maternal tolerance to the fetus during pregnancy, as well as possible causes for rejection of the embryo and complications during pregnancy.

  15. Effect of Regular Circus Physical Exercises on Lymphocytes in Overweight Children

    OpenAIRE

    Cesar Miguel Momesso dos Santos; Fábio Takeo Sato; Maria Fernanda Cury-Boaventura; Silvia Helena Guirado-Rodrigues; Kim Guimaraes Caçula; Cristiane Cassoni Gonçalves Santos; Elaine Hatanaka; Heloisa Helena de Oliveira; Vinicius Coneglian Santos; Gilson Murata; Cristina Neves Borges-Silva; Sandro Massao Hirabara; Tania Cristina Pithon-Curi; Renata Gorjão

    2015-01-01

    Obesity associated with a sedentary lifestyle can lead to changes in the immune system balance resulting in the development of inflammatory diseases. The aim of this study was to compare lymphocyte activation mechanisms between overweight children practicing regular circus physical exercises with non-exercised children. The study comprised 60 pubescent children randomly divided into 4 groups: Overweight Children (OWC) (10.67 ± 0.22 years old), Overweight Exercised Children (OWE) (10.00 ± 0.41...

  16. Interleukin-7 mediates glucose utilization in lymphocytes through transcriptional regulation of the hexokinase II gene

    OpenAIRE

    Chehtane, Mounir; Khaled, Annette R.

    2010-01-01

    The cytokine interleukin-7 (IL-7) has essential growth activities that maintain the homeostatic balance of the immune system. Little is known of the mechanism by which IL-7 signaling regulates metabolic activity in support of its vital function in lymphocytes. We observed that IL-7 deprivation caused a rapid decline in the metabolism of glucose that was attributable to loss of intracellular glucose retention. To identify the transducer of the IL-7 metabolic signal, we examined the expression ...

  17. Dengue virus-specific cross-reactive CD8+ human cytotoxic T lymphocytes.

    OpenAIRE

    Bukowski, J F; Kurane, I; Lai, C J; Bray, M; Falgout, B; Ennis, F A

    1989-01-01

    Stimulation with live dengue virus of peripheral blood mononuclear cells from a dengue virus type 4-immune donor generated virus-specific, serotype-cross-reactive, CD8+, class I-restricted cytotoxic T lymphocytes (CTL) capable of lysing dengue virus-infected cells and cells pulsed with dengue virus antigens of all four serotypes. These CTL lysed autologous fibroblasts infected with vaccinia virus-dengue virus recombinant viruses containing the E gene or several nonstructural dengue virus type...

  18. Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice

    OpenAIRE

    Brachman, Rebecca A.; Lehmann, Michael L.; Maric, Dragan; Herkenham, Miles

    2015-01-01

    We examined whether cells of the adaptive immune system retain the memory of psychosocial stress and thereby alter mood states and CNS function in the host. Lymphocytes from mice undergoing chronic social defeat stress or from unstressed control mice were isolated and adoptively transferred into naive lymphopenic Rag2−/− mice. Changes in affective behavior, hippocampal cell proliferation, microglial activation states, and blood cytokine levels were examined in reconstituted stress-naive mice....

  19. Morphological, immunophenotypic and clinical characteristics of dogs with lymphocytic - plasmacytic duodenitis

    OpenAIRE

    Đorđević Milena; Krstić V.; Krstić N.; Vasiljević Maja; Ilić V.; Vučićević Ivana; Aleksić-Kovačević Sanja

    2012-01-01

    The most important morphological feature of the immune response in lymphocytic-plasmacytic duodenitis (LPD) in dogs is the presence of a mononuclear infiltrate in the duodenal mucosa. The ethiopatogenesis of this disease is still unknown, nor are known all the immunophenotypic characteristics of the infiltrate cells, which would be of help in the elucidation of the pathogenesis of LPD. The study involved 60 adult dogs of different breeds and both sexes: 54 ...

  20. Immuno phenotype of blood lymphocytes in radiation-associated Hodgkin's disease

    International Nuclear Information System (INIS)

    Immuno phenotype of peripheral blood lymphocytes has been studied in Hodgkin's disease including patients exposed to radionuclides of the characteristic Chernobyl pattern. The group of patients under study has been characterized by decreasing T- and NK-cell immunity, such a decrease being more pronounced in radiation-associated Hodgkin's lymphoma. The data obtained as well as the evidence of Epstein-Barr virus activation could explain the aggressiveness of the disease in such patients and the difficulties in their treatment

  1. Fifty cases of human immunodeficiency virus (HIV) infection: immunoultrastructural study of circulating lymphocytes.

    OpenAIRE

    Feremans, W W; Huygen, K.; Menu, R; Farber, C M; de Caluwe, J P; van Vooren, J P; Marcelis, L; Andre, L; Brasseur, M; Bondue, H

    1988-01-01

    The peripheral lymphocytes of 50 cases of human immunodeficiency virus (HIV) infection (13 of acquired immune deficiency syndrome (AIDS), 17 of AIDS related complex (ARC), and 20 healthy carriers) were studied immunoultrastructurally. The prevalence of "tubuloreticular structures" and "tubular confronting cisternae" increased with the progression of the disease. Numerous tubular confronting cisternae were noted in patients presenting with a high serum acid labile alpha-interferon values. The ...

  2. Non-Hodgkin Lymphoma Risk and Variants in Genes Controlling Lymphocyte Development

    OpenAIRE

    Johanna M. Schuetz; Denise Daley; Stephen Leach; Lucia Conde; Berry, Brian R.; Gallagher, Richard P.; Connors, Joseph M; Gascoyne, Randy D.; Bracci, Paige M.; Skibola, Christine F.; Spinelli, John J.; Angela R Brooks-Wilson

    2013-01-01

    Non-Hodgkin lymphomas (NHL) are a heterogeneous group of solid tumours of lymphoid cell origin. Three important aspects of lymphocyte development include immunity and inflammation, DNA repair, and programmed cell death. We have used a previously established case-control study of NHL to ask whether genetic variation in genes involved in these three important processes influences risk of this cancer. 118 genes in these three categories were tagged with single nucleotide polymorphisms (SNPs), wh...

  3. Experimental hyperglycemia induces an increase of monocyte and T-lymphocyte content in adipose tissue of healthy obese women.

    Directory of Open Access Journals (Sweden)

    Michaela Tencerová

    Full Text Available Hyperglycemia represents one of possible mediators for activation of immune system and may contribute to worsening of inflammatory state associated with obesity. The aim of our study was to investigate the effect of a short-term hyperglycemia (HG on the phenotype and relative content of immune cells in circulation and subcutaneous abdominal adipose tissue (SAAT in obese women without metabolic complications.Three hour HG clamp with infusion of octreotide and control investigations with infusion of octreotide or saline were performed in three groups of obese women (Group1: HG, Group 2: Octreotide, Group 3: Saline, n=10 per group. Before and at the end of the interventions, samples of SAAT and blood were obtained. The relative content of immune cells in blood and SAAT was determined by flow cytometry. Gene expression analysis of immunity-related markers in SAAT was performed by quantitative real-time PCR.In blood, no changes in analysed immune cell population were observed in response to HG. In SAAT, HG induced an increase in the content of CD206 negative monocytes/macrophages (p<0.05 and T lymphocytes (both T helper and T cytotoxic lymphocytes, p<0.01. Further, HG promoted an increase of mRNA levels of immune response markers (CCL2, TLR4, TNFα and lymphocyte markers (CD3g, CD4, CD8a, TBX21, GATA3, FoxP3 in SAAT (p<0.05 and 0.01. Under both control infusions, none of these changes were observed.Acute HG significantly increased the content of monocytes and lymphocytes in SAAT of healthy obese women. This result suggests that the short-term HG can modulate an immune status of AT in obese subjects.

  4. Effects of Interval and Continuous Exercise Training on CD4 Lymphocyte Apoptotic and Autophagic Responses to Hypoxic Stress in Sedentary Men

    OpenAIRE

    Tzu-Pin Weng; Shu-Chun Huang; Yu-Fen Chuang; Jong-Shyan Wang

    2013-01-01

    Exercise is linked with the type/intensity-dependent adaptive immune responses, whereas hypoxic stress facilitates the programmed death of CD4 lymphocytes. This study investigated how high intensity-interval (HIT) and moderate intensity-continuous (MCT) exercise training influence hypoxia-induced apoptosis and autophagy of CD4 lymphocytes in sedentary men. Thirty healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n=10) or MCT (sustained 60%V...

  5. Intrahepatic CD8+ lymphocyte trapping during tolerance induction using mushroom derived formulations: A possible role for liver in tolerance induction

    Institute of Scientific and Technical Information of China (English)

    Mony Shuvy; Tiberiu Hershcovici; Cristina Lull-Noguera; Harry Wichers; Ofer Danay; Dan Levanon; Lidya Zolotarov; Yaron Ilan

    2008-01-01

    AIM: To determine the immunomodulatory effect of Shiitake (a mushroom extract),we tested its effect on liver-mediated immune regulation in a model of immune-mediated colitis.METHODS: Four groups of mice were studied.Colitis was induced by intracolonic instillation of TNBS in groups A and B.Groups A and C were treated daily with Shiitake extract,while groups B and D received bovine serum albumin.Mice were evaluated for development of macroscopic and microscopic.The immune effects of Shiitakke were determined by FACS analysis of intra-hepatic and intrasplenic lymphocytes and IFN-γ ELISPOT assay.RESULTS: Administration of Shiitake resulted in marked alleviation of colitis,manifested by significant improvement in the macroscopic and microscopic scores,and by reduction in IFN-γ-producing colonies in group A,compared to group B mice (1.5 pfu/mL vs 3.7 pfu/mL,respectively).This beneficial effect was associated with a significant increase in the intrahepatic CD8+ lymphocyte trapping,demonstrated by an increased intrasplenic/intrahepatic CD4/CD8 lymphocyte ratio.These effects were accompanied by a 17% increase in the number of intrahepatic natural killer T (NKT) cells.A similar effect was observed when Shiitake was administered to animals without disease induction.CONCLUSION: Shiitake extract affected livermediated immune regulation by altering the NKT lymphocyte distribution and increasing intrahepatic CD8+ T lymphocyte trapping,thereby leading to alleviation of immune-mediated colitis.

  6. Protective Role of Cytotoxic T Lymphocytes in Filovirus Hemorrhagic Fever

    Directory of Open Access Journals (Sweden)

    Kelly Lyn Warfield

    2011-01-01

    Full Text Available Infection with many emerging viruses, such as the hemorrhagic fever disease caused by the filoviruses, Marburg (MARV, and Ebola virus (EBOV, leaves the host with a short timeframe in which to mouse a protective immune response. In lethal cases, uncontrolled viral replication and virus-induced immune dysregulation are too severe to overcome, and mortality is generally associated with a lack of notable immune responses. Vaccination studies in animals have demonstrated an association of IgG and neutralizing antibody responses against the protective glycoprotein antigen with survival from lethal challenge. More recently, studies in animal models of filovirus hemorrhagic fever have established that induction of a strong filovirus-specific cytotoxic T lymphocyte (CTL response can facilitate complete viral clearance. In this review, we describe assays used to discover CTL responses after vaccination or live filovirus infection in both animal models and human clinical trials. Unfortunately, little data regarding CTL responses have been collected from infected human survivors, primarily due to the low frequency of disease and the inability to perform these studies in the field. Advancements in assays and technologies may allow these studies to occur during future outbreaks.

  7. Alteration of lymphocyte phenotype and function in sickle cell anemia: Implications for vaccine responses.

    Science.gov (United States)

    Balandya, Emmanuel; Reynolds, Teri; Obaro, Stephen; Makani, Julie

    2016-09-01

    Individuals with sickle cell anemia (SCA) have increased susceptibility to infections, secondary to impairment of immune function. Besides the described dysfunction in innate immunity, including impaired opsonization and phagocytosis of bacteria, evidence of dysfunction of T and B lymphocytes in SCA has also been reported. This includes reduction in the proportion of circulating CD4+ and CD8+ T cells, reduction of CD4+ helper: CD8+ suppressor T cell ratio, aberrant activation and dysfunction of regulatory T cells (Treg ), skewing of CD4+ T cells towards Th2 response and loss of IgM-secreting CD27 + IgM(high) IgD(low) memory B cells. These changes occur on the background of immune activation characterized by predominance of memory CD4+ T cell phenotypes, increased Th17 signaling and elevated levels of C-reactive protein and pro-inflammatory cytokines IL-6 and TNF-α, which may affect the immunogenicity and protective efficacy of vaccines available to prevent infections in SCA. Thus, in order to optimize the use of vaccines in SCA, a thorough understanding of T and B lymphocyte functions and vaccine reactivity among individuals with SCA is needed. Studies should be encouraged of different SCA populations, including sub-Saharan Africa where the burden of SCA is highest. This article summarizes our current understanding of lymphocyte biology in SCA, and highlights areas that warrant future research. Am. J. Hematol. 91:938-946, 2016. © 2016 Wiley Periodicals, Inc. PMID:27237467

  8. RAG2 unleashed: lymphocytes beware

    Science.gov (United States)

    Fugmann, Sebastian D.

    2011-01-01

    The programmed degradation of the RAG2 enzyme upon entry to S phase restricts V(D)J recombination to the G0–G1 phase of the cell cycle. In this issue of Immunity Zhang et al. (2011) show that this is critical to prevent lymphoma formation. PMID:21349423

  9. RAG-2 unleashed: lymphocytes beware.

    Science.gov (United States)

    Fugmann, Sebastian D

    2011-02-25

    The programmed degradation of the RAG-2 enzyme upon entry to S phase restricts V(D)J recombination to the G0-G1 phase of the cell cycle. In this issue of Immunity, Zhang et al. (2011) show that this is critical to prevent lymphoma formation. PMID:21349423

  10. RAG2 unleashed: lymphocytes beware

    OpenAIRE

    Fugmann, Sebastian D.

    2011-01-01

    The programmed degradation of the RAG2 enzyme upon entry to S phase restricts V(D)J recombination to the G0–G1 phase of the cell cycle. In this issue of Immunity Zhang et al. (2011) show that this is critical to prevent lymphoma formation.

  11. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull. 2008; 7(2: 159-166

  12. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  13. Hidden talents of natural killers: NK cells in innate and adaptive immunity

    OpenAIRE

    Cooper, Megan A.; Colonna, Marco; Yokoyama, Wayne M.

    2009-01-01

    Natural killer (NK) cells are innate immune lymphocytes capable of killing target cells and producing immunoregulatory cytokines. Herein, we discuss recent studies that indicate that NK cells span the conventional boundaries between innate and adaptive immunity. For example, it was recently discovered that NK cells have the capacity for memory-like responses, a property that was previously thought to be limited to adaptive immunity. NK cells have also been identified in multiple tissues, and ...

  14. New perspectives for large-scale repertoire analysis of immune receptors.

    Science.gov (United States)

    Boudinot, Pierre; Marriotti-Ferrandiz, Maria Encarnita; Pasquier, Louis Du; Benmansour, Abdenour; Cazenave, Pierre-André; Six, Adrien

    2008-05-01

    In vertebrates, the world of antigenic motifs is matched to large populations of lymphocytes through specific recognition of an epitope by a given receptor unique to a lymphocyte clone. The concept of immune repertoire was proposed to describe this diversity of lymphocyte receptors - Ig and TCR - required by the network of interactions. The immune repertoires became useful tools to describe lymphocyte and receptor populations through the development of the immune system and in pathological situations. Recently, the development of mass technologies made possible a comprehensive survey of immune repertoires at the genome, transcript and protein levels, and some of these techniques have been already adapted to TCR and Ig repertoire analyses. Such approaches generate very big datasets, which necessitates complex and multi-parametric annotations in dedicated databases. They also require new analysis methods, leading to the integration of structure and dynamics of the immune repertoires, at different time scales (immune response, development of the individual, evolution of the species). Such methods may be extended to the analysis of new classes of adaptive-like receptors, which were recently discovered in different invertebrates and in agnathans. Ultimately, they may allow a parallel monitoring of pathogen and immune repertoires addressing the reciprocal influences that decide for the host survival or death. In this review, we first study the characteristics of Ig and TCR repertoires, and we examine several systematic approaches developed for the analysis of these "classical" immune repertoires at different levels. We then consider examples of the recent developments of modeling and statistical analysis, and we discuss their relevance and their importance for the study of the immune diversity. An extended view of immune repertoires is proposed, integrating the diversity of other receptors involved in immune recognition. Also, we discuss how repertoire studies could link

  15. Immune checkpoint‑targeted cancer immunotherapies

    Directory of Open Access Journals (Sweden)

    Julian Swatler

    2016-01-01

    Full Text Available Tumor cells may express on their surface various characteristic antigens that can induce antitumor immunity. However, cancer in human body may induce an immunosuppressive microenvironment that limits immune response to its antigens. For many years scientists have tried to develop an immunotherapy which would induce a potent antitumor immune response and lead to an elimination of the disease. One of the most promising immunotherapies is blockade of immune checkpoints, i.e. a group of costimulatory molecules negatively regulating the immune system. Their blockade would overcome immune tolerance in the tumor microenvironment and amplify antitumor immunity. What’s more, immune checkpoint blockade may turn out even more profitable, as some of immune checkpoints and their ligands are expressed on tumor surface and on tumor infiltrating lymphocytes, contributing to the immunosuppressive cancer microenvironment. Phase III clinical trials have confirmed efficacy of an anti‑CTLA‑4 antibody ipilimumab, thereby leading to its acceptance for the treatment of advanced melanoma. Thanks to promising results of the phase I clinical trials, a breakthrough therapy designation and an early approval for the treatment have been granted to anti‑PD‑1 antibodies ‑ nivolumab (for the treatment of advanced melanoma and advanced non‑small cell lung cancer and pembrolizumab (for the treatment of advanced melanoma and, in the treatment of advanced bladder cancer, an anti‑PD‑L1 antibody ‑ MPDL3280A as well. Other immune checkpoints, such as LAG‑3, TIM‑3, BTLA, B7‑H3 and B7‑H4, are also under early evaluation.

  16. Immune mechanisms in Babesia-infected animals

    International Nuclear Information System (INIS)

    The course of a Babesia infection depends on the species of host and parasite involved. Animals infected with virulent babesias may need chemotherapy before acquired immunity develops. Maintenance of immunity is not dependent on the presence of the parasite. Babesia infections are characteristically of long duration. The immune response to babesias includes both humoral and cellular components. Antibody levels detected in serodiagnostic tests do not relate to levels of resistance to the parasite. Some antibodies, however, appear to be protective. Antiparasitic antibodies may damage parasites in or outside the red cell and act as opsonins. T-cell-deficient and anti-lymphocyte-serum-treated rodents are more susceptible to rodent piroplasms indicating a role for T-cells as either helper cells and/or as mediators of cell-mediated immunity (CMI). There is indirect evidence of CMI, but the cell-mediated mechanisms involved in parasite killing are not known. In domestic animals immunity is largely species- and strain-specific. Antigenic variation by babesias occurs. In rodents, however, there is cross-immunity between different species of rodent piroplasms and between rodent piroplasms and some malaria parasites. Prior infection with agents such as BCG, and Corynebacterium parvum, gives mice non-specific resistance to rodent piroplasms possibly mediated through a soluble non-antibody factor. This factor may also be liberated during piroplasm infections and by being toxic to malaria parasites account for heterologous immunity. Active immunization against babesias has been achieved with avirulent strains, irradiated parasites and dead parasites in adjuvant. During Babesia infections the primary and, to a lesser degree, the secondary immune response to heterologous antigens can be depressed. Maximum depression coincides with peak parasitaemia when antigen priming may be abolished completely. Immunosuppression during Babesia infections can prolong or exacerbate concurrent

  17. Immune checkpoints

    OpenAIRE

    Chawla, Akhil; Philips, Anne V; Alatrash, Gheath; Mittendorf, Elizabeth,

    2014-01-01

    Early clinical trials investigating monoclonal antibodies targeting the T-cell inhibitory receptor programmed cell death 1 (PD-1) and its ligand PD-L1 have shown efficacy in melanoma, non-small cell lung cancer and renal cell carcinoma. We recently demonstrated PD-L1 expression in 20% of triple negative breast cancers suggesting that targeting the PD-1/PD-L1 immune checkpoint may be an effective treatment modality in patients with this disease.

  18. Earthworm Immunity

    Czech Academy of Sciences Publication Activity Database

    Bilej, Martin; Procházková, Petra; Šilerová, Marcela; Josková, Radka

    New York: Landes Biosciences and Springer Science +Business Media, 2010 - (Söderhäll, K.), 66-79. (Advances in Experimental Medicine and Biology. 708). ISBN 978-1-4419-8058-8 R&D Projects: GA ČR GA206/07/0378; GA AV ČR IAA600200704; GA MŠk 2B06155 Institutional research plan: CEZ:AV0Z50200510 Keywords : earthworms * immunity Subject RIV: EC - Immunology

  19. Radiation damage and recovery of the immune system

    International Nuclear Information System (INIS)

    The objectives of the project are concentrated on the problems related to damage and recovery of the immune system after radiation exposure. Mouse populations were studied after whole-body exposure to acute x-ray doses ranging from 1 to 10 Gy. Untreated and treated survivors were studied to assess the number and activity of blood leukocytes and to evaluate the immune functions of spleen lymphocytes. Comparison of the effects of various treatments after different radiation doses should indicate the conditions for optimal intervention to accelerate recovery of the immune system and to prevent radiation death. (R.P.) 27 refs

  20. Immune Response to Ebola Virus Infection

    Directory of Open Access Journals (Sweden)

    Alain Alonso Remedios

    2016-06-01

    Full Text Available Ebola virus belongs to the family Filoviridae and causes a highly lethal hemorrhagic fever. Affected patients show an impaired immune response as a result of the evasion mechanisms employed by the virus. Cathepsin is an enzyme present in the granules of phagocytes which cleaves viral surface glycoproteins, allowing virus entry into the host cell. In addition, this virus is resistant to the antiviral effects of type I interferon, promotes the synthesis of proinflammatory cytokines and induces apoptosis of monocytes and lymphocytes. It also induces an incomplete activation of dendritic cells, thus avoiding the presentation of viral antigens. Although specific antibodies are produced after the first week, their neutralizing capacity is doubtful. The virus evades the immune response and replicates uncontrollably in the host. This paper aims to summarize the main characteristics of the immune response to Ebola virus infection.

  1. Evolution of Multispecificity in an Immune Network

    CERN Document Server

    Harada, K

    1999-01-01

    Divergence in antigen response of the immune network is discussed, based on shape-space modelling. The present model extends the shape-space model by introducing the evolution of specificity of idiotypes. When the amount of external antigen increases, stability of the immune network changes and the network responds to the antigen. It is shown that specific and non-specific responses emerge as a function of antigen levels. A specific response is observed with a fixed point attractor, and a non-specific response is observed with a long-lived chaotic transient state of the lymphocyte population dynamics. The network topology also changes between these two states. The relevance of such a long-lived transient state is discussed with respect to immune function.

  2. Enhancing Immune Responses for Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Shao-An Xue; Hans J Stauss

    2007-01-01

    Although the immune system possesses the means to respond to cancer, it often fails to control the spread of malignancy. Nonetheless, equipping endogenous immunity to release a strong antitumor response has significant advantages over conventional therapies. This review explores some of the options available to accomplish this,focusing first on vaccinations with tumor antigens to stimulate the immune system and empower stronger antitumor responses. We then compare and contrast the so-far limited clinical success of vaccination with the well-documented curative potential of adoptive therapy using T lymphocytes transfer. Finally, we highlight novel approaches using T cell receptor (TCR) gene transfer strategy to exploit allogeneic T cell repertoires in conjunction with receptors selected in vitro for defined MHC/peptide combinations, as a basis for antigen-specific gene therapy of cancers.

  3. Effects of microgravity on the immune system

    Science.gov (United States)

    Sonnenfeld, Gerald; Taylor, Gerald R.

    1991-01-01

    Changes in resistance to bacterial and viral infections in Apollo crew members has stimulated interest in the study of immunity and space flight. Results of studies from several laboratories in both humans and rodents have indicated alterations after space flight that include the following immunological parameters: thymus size, lymphocyte blastogenesis, interferon and interleukin production, natural killer cell activity, cytotoxic T-cell activity, leukocyte subset population distribution, response of bone marrow cells to colony stimulating factors, and delayed hypersensitivity skin test reactivity. The interactions of the immune system with other physiological systems, including muscle, bone, and the nervous system, may play a major role in the development of these immunological parameters during and after flight. There may also be direct effects of space flight on immune responses.

  4. Comparison of Changes in Immunological Parameters in Human Lymphocytes in 2D Versus 3D Clinostats-Goal Towards Microgravity Analog Calibration for Future Space Experiments

    Science.gov (United States)

    Sundaresan, Alamelu; Russomano, Thais; Pellis, Neal R.

    2008-06-01

    Exposure to microgravity may produce changes in the performance of the immunological system at the cellular level as well as in the major physiological systems of the body. Studies in true spaceflight and similar studies in 2D clinostats (Rotating wall vessels) related to decreased immune function in astronaut blood and normal human lymphocytes indicate a decrease in cell proliferation, T cell activation, locomotion and altered lymphocyte signal transduction (Sundaresan and Pellis, 2008, Sundaresan et al., 2004). The present study was designed to investigate whether the proliferation and viability of lymphocytes are reduced by exposure to rotation in a 3D-Clinostat, which is used to simulate microgravity for cells.

  5. Characterization of the lymphocyte membrane receptor for factor H (β1H- globulin) with an antibody to anti-factor H idiotype

    OpenAIRE

    Lambris, JD; Ross, GD

    1982-01-01

    Antibody to the binding site (idiotype) of anti-factor H was shown to have specificity for both B lymphocyte membrane H receptors and C3b. Goat F(ab’)(2) anti-human H was purified by absorption and elution from H agarose and used for rabbit immunization to produce anti-anti-H (aaH). After absorption with nonimmune goat IgG, (125)I-labeled aaH bound to B lymphocytes and to sheep erythrocytes coated with C3b (EC3b) but did not bind to T lymphocytes or to EC3d. All B cell- and C3b-specific activ...

  6. Triple cancer: chronic lymphocytic leukemia with bladder and prostate carcinoma.

    Science.gov (United States)

    Gajendra, Smeeta; Sharma, Rashi; Sahoo, Manas Kumar

    2015-08-01

    B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is a common lymphoproliferative disorder with an increased risk of developing subsequent neoplasms of epithelial and mesenchymal origin. The decreased immunity and B-cell dysfunction in CLL probably accounts for this emergence of second malignancies. We report a case of synchronous bladder transitional cell carcinoma (TCC) and prostatic carcinoma with CLL. A 74-year-old male who underwent transurethral resection of the prostate (TURP) for benign prostatic hyperplasia 2 years before, presented with recurrent urinary tract infection. Peripheral blood smear revealed leukocytosis with absolute lymphocytosis (absolute lymphocyte count: 37870 cells/mm³). Flow cytometric immunophenotyping revealed 75% abnormal lymphoid cells which were positive for CD 19, CD5, CD23, CD22, CD200, CD20 (moderate) with lambda light chain restriction and negative for CD3, CD10, FMC7, CD38, CD138, IgM, CD103, CD123. F Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) showed increased metabolic activity of the left lateral wall of the urinary bladder extending to the left UV junction, adjacent part of trigone and bladder neck region along with multiple heterogeneous enhancing areas with increased FDG avidity within the prostate. Transurethral resection of the bladder tumour by cystoscopy was performed. Histopathology showed high grade, muscle invasive urothelial carcinoma. Due to presence of uptake in the prostate, transurethral resection of the prostate was done and histopathology revealed adenocarcinoma of prostate (prostate specific antigen- positive), Gleason grade III+III and Gleason score 6. A high index of suspicion is required to detect synchronous and metachronous malignancies. Ancillary studies such as immunohistochemistry, flow cytometry and PET/CT are often essential for detection and an accurate diagnosis. PMID:26277675

  7. Importance of B Lymphocytes and the IgG-Binding Protein Sbi in Staphylococcus aureus Skin Infection.

    Science.gov (United States)

    Zhao, Fan; Chong, Anita S; Montgomery, Christopher P

    2016-01-01

    Recurrent Staphylococcus aureus infections are common, suggesting that immunity elicited by these infections is not protective. We previously reported that S. aureus skin infection (SSTI) elicited antibody-mediated immunity against secondary SSTI in BALB/c mice. In this study, we investigated the role of humoral immunity and the IgG-binding proteins Sbi and SpA in S. aureus SSTI. We found that B lymphocyte-deficient μMT mice were highly susceptible to infection, compared with congenic BALB/c mice. Importantly, transfer of immune serum protected μMT mice, demonstrating an appropriate response to protective antibody. We found that deletion of sbi, but not spa, impaired virulence, as assessed by skin lesion severity, and that Sbi-mediated virulence required B lymphocytes/antibody. Furthermore, neither Sbi nor SpA impaired the elicited antibody response or protection against secondary SSTI. Taken together, these findings highlight a B lymphocyte/antibody-dependent role of Sbi in the pathogenesis of S. aureus SSTI, and demonstrate that neither Sbi nor SpA interfered with elicited antibody-mediated immunity. PMID:26828524

  8. Importance of B Lymphocytes and the IgG-Binding Protein Sbi in Staphylococcus aureus Skin Infection

    Directory of Open Access Journals (Sweden)

    Fan Zhao

    2016-01-01

    Full Text Available Recurrent Staphylococcus aureus infections are common, suggesting that immunity elicited by these infections is not protective. We previously reported that S. aureus skin infection (SSTI elicited antibody-mediated immunity against secondary SSTI in BALB/c mice. In this study, we investigated the role of humoral immunity and the IgG-binding proteins Sbi and SpA in S. aureus SSTI. We found that B lymphocyte-deficient μMT mice were highly susceptible to infection, compared with congenic BALB/c mice. Importantly, transfer of immune serum protected μMT mice, demonstrating an appropriate response to protective antibody. We found that deletion of sbi, but not spa, impaired virulence, as assessed by skin lesion severity, and that Sbi-mediated virulence required B lymphocytes/antibody. Furthermore, neither Sbi nor SpA impaired the elicited antibody response or protection against secondary SSTI. Taken together, these findings highlight a B lymphocyte/antibody-dependent role of Sbi in the pathogenesis of S. aureus SSTI, and demonstrate that neither Sbi nor SpA interfered with elicited antibody-mediated immunity.

  9. Diagnosis of drug hypersensitivity: lymphocyte transformation test and cytokines

    International Nuclear Information System (INIS)

    For all types of allergic reactions including immediate type of reactions, types II and III reactions as well as delayed-type reactions the recognition of the antigen by specifically sensitized T-lymphocytes is a prerequisite. Evidences for the key role of T-lymphocytes in the pathophysiology of allergic drug reactions are positive patch test reactions and the LTT. The proliferative response that can be measured by means of the incorporation of 3H-thymidine during DNA synthesis can be expressed as stimulation index (SI) which is the relation between the cell proliferation with antigen compared without antigen. In addition drug-specific activation of PBMC consistently resulted in IL-5 expression and secretion. The sensitivity of the LTT for the detection of drug sensitization could be improved up to 92% by the measurement of released interleukin-5. The expression and secretion of other cytokines such as IFN-γ and IL-10 was less consistently and had a diagnostic sensitivity of 36 and 50%, respectively. Microarrays are a promising new technical platform to look for better markers which can be used as a read out in the LTT and other similar assays and to study pharmacological interactions between drugs including cytokines such as interferons and the immune system

  10. Reactive oxygen species-mediated bacterial killing by B lymphocytes.

    Science.gov (United States)

    Kovács, István; Horváth, Magdolna; Lányi, Árpád; Petheő, Gábor L; Geiszt, Miklós

    2015-06-01

    Regulated production of ROS is mainly attributed to Nox family enzymes. In neutrophil granulocytes and macrophages, Nox2 has a crucial role in bacterial killing, and the absence of phagocytic ROS production leads to the development of CGD. Expression of Nox2 was also described in B lymphocytes, where the role of the enzyme is still poorly understood. Here, we show that peritoneal B cells, which were shown recently to possess phagocytic activity, have a high capacity to produce ROS in a Nox2-dependent manner. In phagocytosing B cells, intense intraphagosomal ROS production is detected. Finally, by studying 2 animal models of CGD, we demonstrate that phagocyte oxidase-deficient B cells have a reduced capacity to kill bacteria. Our observations extend the number of immune cell types that produce ROS to kill pathogens. PMID:25821233

  11. Chronic Lymphocytic Inflammation Specifies the Organ Tropism of Prions

    Science.gov (United States)

    Heikenwalder, Mathias; Zeller, Nicolas; Seeger, Harald; Prinz, Marco; Klöhn, Peter-Christian; Schwarz, Petra; Ruddle, Nancy H.; Weissmann, Charles; Aguzzi, Adriano

    2005-02-01

    Prions typically accumulate in nervous and lymphoid tissues. Because proinflammatory cytokines and immune cells are required for lymphoid prion replication, we tested whether inflammatory conditions affect prion pathogenesis. We administered prions to mice with five inflammatory diseases of the kidney, pancreas, or liver. In all cases, chronic lymphocytic inflammation enabled prion accumulation in otherwise prion-free organs. Inflammatory foci consistently correlated with lymphotoxin up-regulation and ectopic induction of FDC-M1+ cells expressing the normal cellular prion protein PrPC. By contrast, inflamed organs of mice lacking lymphotoxin-α or its receptor did not accumulate the abnormal isoform PrPSc, nor did they display infectivity upon prion inoculation. By expanding the tissue distribution of prions, chronic inflammatory conditions may act as modifiers of natural and iatrogenic prion transmission.

  12. Does plutonium intake in workers affect lymphocyte function?

    International Nuclear Information System (INIS)

    Measurements of mononuclear cells in peripheral blood of persons with long term internal depositions of plutonium indicate a preferential reduction in suppressor T-lymphocytes (T/sub s/) in some individuals. The decrease in T/sub s/ cells is apparently due to altered radiosensitivity, which is domonstrated in cultured cells subjected to in vitro x-ray radiation. The increase in ratios correlates with the quantity of plutonium deposition in these subjects, but there are wide individual differences. Confirmatory studies are needed in other persons with long term alpha or chronic gamma radiation exposure. If confirmed, the implications would include recognition of a potential mechanism for an enhanced immune system reactivity in some individuals exposed to chronic low level radiation. 13 refs., 1 fig., 1 tab

  13. Immune activity evaluation of GPC3 peptides recognized by HLA-A11 restricted T lymphocytes in hepatocellular carcinoma patients%GPC3特异性HLA-A11限制的T淋巴细胞表位肽免疫活性检测

    Institute of Scientific and Technical Information of China (English)

    孙斌; 郑加生; 陈德喜; 李雯; 计云霞; 郭向华; 杨晓珍; 郝美君; 李伟华; 白飞云; 王延军

    2014-01-01

    目的:设计合成人类白细胞抗原(HLA)-A11限制性T细胞识别的磷脂酰肌醇蛋白聚糖3(GPC3)多肽,并检测其免疫原性和反应性。方法利用BIMAS 和SYFPEITHI评分系统评价GPC3多肽与HLA-A11分子的结合能力,预测出相应的抗原谱,合成HLA-A1101限制性GPC3多肽库;流式细胞仪检测HCC患者HLA-A11分子的表达;多肽刺激外周血淋巴细胞,酶联免疫斑点试验(ELISPOT)检测T细胞对GPC3多肽的反应性。结果流式细胞仪检测32例HCC患者,7例HLA-A11分子表达阳性(21.9%);ELISPOT检测发现17例(53.1%)HCC患者的T细胞应答阳性,7例(21.9%)HLA-A11表型检测阳性的 HCC患者,T细胞应答结果成强阳性。HLA-A11限制性GPC3多肽应答率符合人群中相应基因位点的自然表达率。结论 GPC3多肽设计合理,具有良好的免疫原性和反应性。%Objective To design and synthesize GPC3 peptides recognized by HLA -A11 - restricted T lymphocytes, and to detect their immunogenicity and reactivity. Methods The GPC3 peptides and HLA-A11 molecules were evaluated, and the corresponding antigen spectrum was predicted by BIMAS and SYFPEITHI scoring system. HLA-A1101 which restricted GPC3 peptide library was synthesized; the expression of HLA-A11 molecules in hepatocell-lular carcinoma (HCC) patients was tested by flow cytometry; peripheral blood lymphocytes were stimulated with peptides, and reactive T lymphocytes were detected with ELISPOT for secretion of IFN-γ. Results Thirty-two HCC patients were detected by flow cytometry for HLA-A11 molecular expression with 7 cases (21.9%) positive. By ELISPOT, 17 cases were detected for T lymphocytes respose with positive. Meanwhile, the T lymphocytes responses in the 7 HCC patients were de-tected as strongly positive, showing that the HLA-A11 restricted GPC3 peptide response rate was consisted with the natural expression rate of the corresponding gene locus. Conclusion The GPC3

  14. Effect of space flight on cell-mediated immunity

    Science.gov (United States)

    Mandel, A. D.; Balish, E.

    1977-01-01

    The cell-mediated immune response to Listeria monocytogenes was studied in rats subjected to 20 days of flight aboard the Soviet biosatellite Kosmos 7820. Groups of rats were immunized with 1,000,000 formalin-killed Listeria suspended in Freunds Complete Adjuvant, 5 days prior to flight. Immunized rats subjected to the same environmental factors as the flight rats, except flight itself, and immunized and nonimmunized rats held in a normal animal colony served as controls. Following recovery, lymphocyte cultures were harvested from spleens of all rats, cultured in vitro in the presence of L. monocytogenes antigens, Phytohemagglutinin, Conconavlin A, or purified protein derivative (PPD), and measured for their uptake of H-3-thymidine. Although individual rats varied considerably, all flight and immunized control rats gave a blastogenic response to the Listeria antigens and PPD. With several mitogens, the lymphocytes of flight rats showed a significantly increased blastogenic response over the controls. The results of this study do not support a hypothesis of a detrimental effect of space flight on cell-mediated immunity. The data suggest a possible suppressive effect of stress and gravity on an in vitro correlate of cell-mediated immunity.

  15. Lasting monitoring of immune state in patients with coronary atherosclerosis

    Science.gov (United States)

    Malinova, Lidia I.; Denisova, Tatyana P.; Tuchin, Valery V.

    2007-02-01

    Immune state monitoring is an expensive, invasive and sometimes difficult necessity in patients with different disorders. Immune reaction dynamics study in patients with coronary atherosclerosis provides one of the leading components to complication development, clinical course prognosis and treatment and rehabilitation tactics. We've chosen intravenous glucose injection as metabolic irritant in the following four groups of patients: men with proved coronary atherosclerosis (CA), non insulin dependent diabetes mellitus (NIDDM), men hereditary burden by CA and NIDDM and practically healthy persons with longlivers in generation. Immune state parameters such as quantity of leukocytes and lymphocytes, circulating immune complexes levels, serum immunoglobulin levels, HLA antigen markers were studied at 0, 30 and 60 minutes during glucose loading. To obtain continues time function of studied parameters received data were approximated by polynomials of high degree with after going first derivatives. Time functions analyze elucidate principally different dynamics studied parameters in all chosen groups of patients, which couldn't be obtained from discontinuous data compare. Leukocyte and lymphocyte levels dynamics correlated HLA antigen markers in all studied groups. Analytical estimation of immune state in patients with coronary atherosclerosis shows the functional "margin of safety" of immune system state under glucose disturbance. Proposed method of analytical estimation also can be used in immune system monitoring in other groups of patients.

  16. Influence of radioiodine therapy on the immuno phenotype of peripheral blood lymphocytes of patients with thyroid cancer of different age

    International Nuclear Information System (INIS)

    The authors present the results of a study of the phenotypic composition of blood lymphocytes in patients with differentiated thyroid cancer of different all age before and on day 6 after radioiodine therapy. The phenotypic profile of peripheral blood cells was determined in patients of three age groups: patients aged under 18 years (group 1), patients whose age was within the range 19 to 40 years (group 2), and patients older than 41 years (group 3). The studies have shown that in patients with thyroid cancer, abnormalities developed in the composition of peripheral blood lymphocytes, which were more pronounced in elderly patients. Under the influence of radioiodine, disturbances in the immune system of patients are aggravated. The most significant after-effects of radioiodine therapy that had been identified in patients of all age groups, were represented by a significant decrease in the number of B-lymphocytes, an increase in natural killer cells and CD95+ lymphocytes. Furthermore, it was found that radioiodine has the most significant effect on the immune system of children and adolescents. In this age group, the content of lymphocyte subpopulations is changing: CD4+, CD8+, IRI, CD19+, CD16+CD56+, CD95+ and HLA-DR, which suggests the need for further dynamic studies in this age group of patients, which is the most sensitive to radioiodine effect in order to determine the extent of immunological disorders and the terms of their recovery

  17. Sudden unexpected death associated with lymphocytic thyroiditis

    DEFF Research Database (Denmark)

    Vestergaard, Vibeke; Drostrup, Dorthe Høj; Thomsen, Jørgen L

    2007-01-01

    performed blind with semiquantitative assessment of the following six parameters: (a) height of the follicular epithelium, (b) the amount of lymphocytes, (c) the presence of plasma cells, (d) hyperplastic follicular changes, (e) oxyphilic changes, and (f) fibrosis. The most striking result was the finding...... of extensive lymphocytic infiltration of the thyroid parenchyma in five of the 124 cases, of which four belonged in the group of 'unknown cause of death'. This discovery leads to reflections regarding lymphocytic thyroiditis as a cause of death, either by itself or in combination with other disorders...

  18. Exploiting death: apoptotic immunity in microbial pathogenesis.

    Science.gov (United States)

    Ucker, D S

    2016-06-01

    Innate immunity typically is responsible for initial host responses against infections. Independently, nucleated cells that die normally as part of the physiological process of homeostasis in mammals (including humans) suppress immunity. Specifically, the physiological process of cell death (apoptosis) generates cells that are recognized specifically by viable cells of all types and elicit a profound transient suppression of host immunity (termed 'innate apoptotic immunity' (IAI)). IAI appears to be important normally for the maintenance of self-tolerance and for the resolution of inflammation. In addition, pathogens are able to take advantage of IAI through a variety of distinct mechanisms, to enable their proliferation within the host and enhance pathogenicity. For example, the protist pathogen Leishmania amazonensis, at its infective stage, mimics apoptotic cells by expressing apoptotic-like protein determinants on the cell surface, triggering immunosuppression directly. In contrast, the pathogenic bacterium Listeria monocytogenes triggers cell death in host lymphocytes, relying on those apoptotic cells to suppress host immune control and facilitate bacterial expansion. Finally, although the inhibition of apoptotic cell death is a common attribute of many viruses which facilitates their extended replication, it is clear that adenoviruses also reprogram the non-apoptotic dead cells that arise subsequently to manifest apoptotic-like immunosuppressive properties. These three instances represent diverse strategies used by microbial pathogens to exploit IAI, focusing attention on the potency of this facet of host immune control. Further examination of these cases will be revealing both of varied mechanisms of pathogenesis and the processes involved in IAI control. PMID:26943319

  19. PATHOGENESIS OF IMMUNE ALTERATIONS AND CORRECTIVE ROLE OF AMLODIPINE IN EXPERIMENTAL CHRONIC RENAL FAILURE

    Directory of Open Access Journals (Sweden)

    M. V. Osikov

    2016-01-01

    Full Text Available The purpose of this study was to assess some mechanisms of changes in immune state, and to evaluate a role of amlodipine, a known calcium channel blocker, as a potential corrective drug in experimental chronic renal failure (CRF. An animal CRF model was produced in rats by a two-stage operative resection of 5/6 of the renal tissue. Amlodipine is used per os at a daily dose of 0.25 mg/kg for 7 days. Flow cytofluorimetric approach was used to discern peripheral blood lymphocytes: CD3+ (mainly, T lymphocytes, CD45RA+ (mainly, B cells, as well as the following cell markers: Annexin 5-FITC+/7-AAD- (early apoptosis, Annexin 5-FITC+/7-AAD+ (late apoptosis and, in part, necrotic cells. Moreover, we have measured serum concentrations of urea, creatinine, phosphate, total calcium, parathyroid hormone (PTH, IL-1β, IL-4, interferon-γ, superoxide dismutase (SOD and catalase activities. Evaluation of Th1- and Th2-dependent immune response was carried out, respectively, by detection of delayed-type hypersensitivity, and scoring the antibody-forming cells in rat spleen induced by immunization with allogeneic erythrocytes. Primary, secondary and final products of lipid peroxidation were evaluated in lipid extracts from peripheral blood lymphocytes. Changes of immune state in CRF included depression of Th1 and Th2 dependent immune response, reduced number of lymphocytes bearing T and В cell markers, increased IL-1β concentrations in blood, along with decreased amounts of IFNγ and IL-4. Probable pathogenesis of the altered immune state may be associated with increased number of peripheral lymphocytes being at early and late stages of apoptosis/necrosis, elevated blood levels of IL-1β, total calcium, parathyroid hormone, reduced concentrations of IFNγ, and increased contents of primary, secondary and final peroxidation products in peripheral blood lymphocytes, being accompanied by inhibition of the SOD and catalase activity in blood plasma

  20. Sweet Syndrome in a Patient with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Curious Lymphocyte/Neutrophil Fluctuations

    OpenAIRE

    Çiğdem Usul Afşar; Semra Paydaş; Meral Günaldı; Berna Bozkurt Duman; Vehbi Erçolak; Suzan Zorludemir; Arbil Açıkalın

    2013-01-01

    Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by tender, red inflammatory nodules or papules that occur in association with infection, malignancy, connective tissue disease, or following exposure to certain drugs. Here, we present Sweet syndrome in a case with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) which is a relatively rare co-occurrence. Conflict of interest:None declared.

  1. Sweet Syndrome in a Patient with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Curious Lymphocyte/Neutrophil Fluctuations

    Directory of Open Access Journals (Sweden)

    Çiğdem Usul Afşar

    2013-12-01

    Full Text Available Sweet syndrome, also referred to as acute febrile neutrophilic dermatosis, is characterized by tender, red inflammatory nodules or papules that occur in association with infection, malignancy, connective tissue disease, or following exposure to certain drugs. Here, we present Sweet syndrome in a case with small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL which is a relatively rare co-occurrence.

  2. Modeled microgravity-induced protein kinase C isoform expression in human lymphocytes

    Science.gov (United States)

    Sundaresan, A.; Risin, D.; Pellis, N. R.

    2004-01-01

    In long-term space travel, the crew is exposed to microgravity and radiation that invoke potential hazards to the immune system. T cell activation is a critical step in the immune response. Receptor-mediated signaling is inhibited in both microgravity and modeled microgravity (MMG) as reflected by diminished DNA synthesis in peripheral blood lymphocytes and their locomotion through gelled type I collagen. Direct activation of protein kinase C (PKC) bypassing cell surface events using the phorbol ester PMA rescues MMG-inhibited lymphocyte activation and locomotion, whereas the calcium ionophore ionomycin had no rescue effect. Thus calcium-independent PKC isoforms may be affected in MMG-induced locomotion inhibition and rescue. Both calcium-dependent isoforms and calcium-independent PKC isoforms were investigated to assess their expression in lymphocytes in 1 g and MMG culture. Human lymphocytes were cultured and harvested at 24, 48, 72, and 96 h, and serial samples were assessed for locomotion by using type I collagen and expression of PKC isoforms. Expression of PKC-alpha, -delta, and -epsilon was assessed by RT-PCR, flow cytometry, and immunoblotting. Results indicated that PKC isoforms delta and epsilon were downregulated by >50% at the transcriptional and translational levels in MMG-cultured lymphocytes compared with 1-g controls. Events upstream of PKC, such as phosphorylation of phospholipase Cgamma in MMG, revealed accumulation of inactive enzyme. Depressed calcium-independent PKC isoforms may be a consequence of an upstream lesion in the signal transduction pathway. The differential response among calcium-dependent and calcium-independent isoforms may actually result from MMG intrusion events earlier than PKC, but after ligand-receptor interaction.

  3. Increased presence of effector lymphocytes during Helicobacter hepaticus-induced colitis

    Institute of Scientific and Technical Information of China (English)

    Sarah J McCaskey; Elizabeth A Rondini; Jonathan F Clinthorne; Ingeborg M Langohr; Elizabeth M Gardner; Jenifer I Fenton

    2012-01-01

    AIM:To identify and characterize drosophila mothers against decapentaplegic (SMAD)3-dependent changes in immune cell populations following infection with HeliCobacter hepaticus (H.hepaticus).METHODS:SMAD3-/-(n =19) and colitis-resistant SMAD3+/-(n =24) mice (8-10 wk of age) were infected with H.hepaticus and changes in immune cell populations [T lymphocytes,natural killer (NK) cells,T regulatory cells] were measured in the spleen and mesenteric lymph nodes (MsLNs) at 0 d,3 d,7 d and 28 d post-infection using flow cytometry.Genotypedependent changes in T lymphocytes and granzyme B+ cells were also assessed after 28 d in proximal colon tissue using immunohistochemistry.RESULTS:As previously observed,SMAD3-/-,but not SMAD3+/-mice,developed colitis,peaking at 4 wk post-infection.No significant changes in T cell subsets were observed in the spleen or in the MsLNs between genotypes at any time point.However,CD4+ and CD8+/CD62L10 cells,an effector T lymphocyte population,as well as NK cells (NKp46/DX5+) were significantly higher in the MsLNs of SMAD3-/-mice at 7 d and 28 d post-infection.In the colon,a higher number of CD3+ cells were present in SMAD3-/-compared to SMAD3+/-mice at baseline,which did not significantly change during infection.However,the number of granzyme B+ cells,a marker of cytolytic lymphocytes,significantly increased in SMAD3-/-mice 28 d post-infection compared to both SMAD3+/-mice and to baseline values.This was consistent with more severe colitis development in these animals.CONCLUSION:Data suggest that defects in SMAD3signaling increase susceptibility to H.hepaticus-induced colitis through aberrant activation and/or dysregulation of effector lymphocytes.

  4. INFLUENCE OF MODIFIED BIOFLAVONOIDS UPON EFFECTOR LYMPHOCYTES IN MURINE MODEL OF CONTACT SENSITIVITY

    Directory of Open Access Journals (Sweden)

    D. Z. Albegova

    2015-01-01

    Full Text Available Contact sensitivity reaction (CSR to 2,4-dinitrofluorobenzene (DNFB in mice is a model of in vivo immune response, being an experimental analogue to contact dermatitis in humans. CSR sensitization phase begins after primary contact with antigen, lasting for 10-15 days in humans, and 5-7 days, in mice. Repeated skin exposure to the sensitizing substance leads to its recognition and triggering immune inflammatory mechanisms involving DNFB-specific effector T lymphocytes. The CSR reaches its maximum 18-48 hours after re-exposure to a hapten. There is only scarce information in the literature about effects of flavonoids on CSR, including both stimulatory and inhibitory effects. Flavonoids possessed, predominantly, suppressive effects against the CSR development. In our laboratory, a model of contact sensitivity was reproduced in CBA mice by means of cutaneous sensitization by 2,4-dinitrofluorobenzene. The aim of the study was to identify the mechanisms of immunomodulatory action of quercetin dihydrate and modified bioflavonoids, using the method of adoptive transfer contact sensitivity by splenocytes and T-lymphocytes. As shown in our studies, a 30-min pre-treatment of splenocytes and T-lymphocytes from sensitized mice with modified bioflavonoids before the cell transfer caused complete prevention of contact sensitivity reaction in syngeneic recipient mice. Meanwhile, this effect was not associated with cell death induction due to apoptosis or cytotoxicity. Quercetin dihydrate caused only partially suppression the activity of adaptively formed T-lymphocytes, the contact sensitivity effectors. It was shown that the modified bioflavonoid more stronger suppress adoptive transfer of contact sensitivity in comparison with quercetin dehydrate, without inducing apoptosis of effector cells. Thus, the modified bioflavonoid is a promising compound for further studies in a model of contact sensitivity, due to its higher ability to suppress transfer of CSR with

  5. Effects of iron overload on the immune system.

    Science.gov (United States)

    Walker, E M; Walker, S M

    2000-10-01

    Iron and its binding proteins have immunoregulatory properties, and shifting of immunoregulatory balances by iron excess or deficiency may produce severe, deleterious physiological effects. Effects of iron overload include decreased antibody-mediated and mitogen-stimulated phagocytosis by monocytes and macrophages, alterations in T-lymphocyte subsets, and modification of lymphocyte distribution in different compartments of the immune system. The importance of iron in regulating the expression of T-lymphocyte cell surface markers, influencing the expansion of different T-cell subsets, and affecting immune cell functions can be demonstrated in vitro and in vivo. The poor ability of lymphocytes to sequester excess iron in ferritin may help to explain the immune system abnormalities in iron-overloaded patients. Iron overload as seen in hereditary hemochromatosis patients enhances suppressor T-cell (CD8) numbers and activity, decreases the proliferative capacity, numbers, and activity of helper T cells (CD4) with increases in CD8/CD4 ratios, impairs the generation of cytotoxic T cells, and alters immunoglobulin secretion when compared to treated hereditary hemochromatosis patients or controls. A correlation has recently been found between low CD8+ lymphocyte numbers, liver damage associated with HCV positivity, and severity of iron overload in beta-thalassemia major patients. Iron overload, with its associated increases of serum iron levels and transferrin saturation, may cause a poor response to interferon therapy. Iron overload with hyperferremia is associated with suppressed functions of the complement system (classic or alternative types). High plasma ferritin content in patients with chronic, diffuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, and hereditary hemochromatosis may induce the development of anti-ferritin antibodies with the production of circulating immune complexes. Increased body stores of iron in

  6. Age- and dose-related alteration of in vitro mixed lymphocyte culture response of blood lymphocytes from A-bomb survivors

    International Nuclear Information System (INIS)

    The responsiveness of peripheral blood lymphocytes to allogenic antigens in mixed lymphocyte culture (MLC) was measured in 139 atomic bomb survivors. The study revealed a significant decrease in MLC with increasing dose of previous radiation exposure. This decline was remarkable in the survivors who were older than 15 at the time of the bomb (ATB). The results suggest a possible relationship between the recovery of T-cell-related function and the thymic function which processes mature T-cells for the immune system. Thus it may be that, in the advanced age ATB group, the thymus function has started to involute allowing less recovery of T-cell function compared to young survivors who have adequate processing T-cell activity. (author)

  7. Air pollution exposure during critical time periods in gestation and alterations in cord blood lymphocyte distribution: a cohort of livebirths

    Directory of Open Access Journals (Sweden)

    Herr Caroline EW

    2010-08-01

    Full Text Available Abstract Background Toxic exposures have been shown to influence maturation of the immune system during gestation. This study investigates the association between cord blood lymphocyte proportions and maternal exposure to air pollution during each gestational month. Methods Cord blood was analyzed using a FACSort flow cytometer to determine proportions of T lymphocytes (CD3+ cells and their subsets, CD4+ and CD8+, B lymphocytes (CD19+ and natural killer (NK cells. Ambient air concentrations of 12 polycyclic aromatic hydrocarbons (PAH and particulate matter 2.5 were measured using fixed site monitors. Arithmetic means of these pollutants, calculated for each gestational month, were used as exposure metrics. Data on covariates were obtained from medical records and questionnaires. Multivariable linear regression models were fitted to estimate associations between monthly PAH or PM2.5 and cord blood lymphocytes, adjusting for year of birth and district of residence and, in further models, gestational season and number of prior live births. Results The adjusted models show significant associations between PAHs or PM2.5 during early gestation and increases in CD3+ and CD4+ lymphocytes percentages and decreases in CD19+ and NK cell percentages in cord blood. In contrast, exposures during late gestation were associated with decreases in CD3+ and CD4+ fractions and increases in CD19+ and NK cell fractions. There was no significant association between alterations in lymphocyte distribution and air pollution exposure during the mid gestation. Conclusions PAHs and PM2.5 in ambient air may influence fetal immune development via shifts in cord blood lymphocytes distributions. Associations appear to differ by exposure in early versus late gestation.

  8. 21 CFR 864.8500 - Lymphocyte separation medium.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lymphocyte separation medium. 864.8500 Section 864...) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8500 Lymphocyte separation medium. (a) Identification. A lymphocyte separation medium is a device used to isolate lymphocytes...

  9. Lymphocytes from the site of disease but not blood lymphocytes indicate the cause of arthritis.

    OpenAIRE

    Ford, D K; da Roza, D; Schulzer, M

    1985-01-01

    The [3H]thymidine uptake procedure for measuring lymphocyte responses was applied to lymphocytes derived concurrently from synovial effusions and from peripheral blood. The stimulating antigens were crude preparations of those micro-organisms that are related to the enteritis and the non-gonococcal urethritis that precipitate reactive arthritis. Salmonella, shigella, and campylobacter antigens stimulated synovial but not peripheral blood lymphocytes in eight cases of enteric reactive arthriti...

  10. Anti-cytotoxic T lymphocyte antigen-4 antibodies in melanoma

    Directory of Open Access Journals (Sweden)

    Tosti G

    2013-10-01

    Full Text Available Giulio Tosti, Emilia Cocorocchio, Elisabetta PennacchioliDivisione Melanomi e Sarcomi, Istituto Europeo di Oncologia, Milano, ItalyAbstract: Approaches aimed at enhancement of the tumor specific response have provided proof for the rationale of immunotherapy in cancer, both in animal models and in humans. Ipilimumab, an anti-cytotoxic T lymphocyte antigen-4 (CTLA-4 antibody, is a new generation immunotherapeutic agent that has shown activity in terms of disease free and overall survival in metastatic melanoma patients. Its use was approved by the US Food and Drug Administration in March 2011 to treat patients with late stage melanoma that has spread or that cannot be removed by surgery. The mechanism of action of CTLA-4 antibodies in the activation of an antitumor immune response and selected clinical studies of ipilimumab in advanced melanoma patients are discussed. Ipilimumab treatment has been associated with immune related adverse events due to T-cell activation and proliferation. Most of these serious adverse effects are associated with the gastrointestinal tract and include severe diarrhea and colitis. The relationship between immune related adverse events and antitumor activity associated with ipilimumab was explored in clinical studies. Potential biomarkers predictive for clinical response and survival in patients treated with anti-CTLA-4 therapy are presently under investigation. Besides the conventional patterns of response and stable disease as defined by standard Response Evaluation Criteria in Solid Tumors criteria, in subsets of patients, ipilimumab has shown patterns of delayed clinical activity which were associated with an improved overall survival. For this reason a new set of response criteria for tumor immunotherapy has been proposed, which was termed immune related response criteria. These new criteria are presently used to better analyze clinical activity of immunotherapeutic regimens. Ipilimumab is currently under

  11. Distribution of Lymphocytes in the Mucosa Associated Lymphoid Tissues (MALT of Naturally Occurring Infectious Bursal Disease (IBD in Chicken

    Directory of Open Access Journals (Sweden)

    M. M. Uddin*, M. Z. I. Khan1, K. N. Islam, A. S. M. G. Kibria, G. N. Adhikary2, M. N. H. Parvez3, J. Basu, M. B. Uddin4 and M. M. Rahman5

    2010-04-01

    Full Text Available This study was aimed to investigate changes in the number and distribution of lymphocytes in the mucosa associated lymphoid tissues (MALT of digestive tract (proventriculus, duodenum, jejunum, ileum, cecum and cecal tonsils and respiratory system (lungs of chicken infected by Infectious Bursal Disease Virus (IBDV. Samples were divided into two groups; IBDV infected group (21, 24 and 30 days old and control group (non infected birds; 21 days old. Haematoxylin and eosin stained slides were prepared for microscopic studies to observe the distribution and the number of lymphocytes in the mucosa of the digestive tract and respiratory system. Lymphocytes were significantly (P<0.05 lower in proventriculus, duodenum, jejunum, ileum, cecum, cecal tonsils and lungs of IBDV infected chickens than the control. Moreover, the reduction in lymphocytes number was maximum in duodenum and cecal tonsils, while minimal in lungs. Depletion of lymphocyte was mainly in the lamina propria and the core of the villi and depletion increased with the advance of age of IBDV infected chicken. These results demonstrate that IBDV destroys the lymphocytes of the MALT and suppresses the immunity.

  12. Loss of signal transduction and inhibition of lymphocyte locomotion in a ground-based model of microgravity

    Science.gov (United States)

    Sundaresan, Alamelu; Risin, Diana; Pellis, Neal R.; McIntire, L. V. (Principal Investigator)

    2002-01-01

    Inflammatory adherence to, and locomotion through the interstitium is an important component of the immune response. Conditions such as microgravity and modeled microgravity (MMG) severely inhibit lymphocyte locomotion in vitro through gelled type I collagen. We used the NASA rotating wall vessel bioreactor or slow-turning lateral vessel as a prototype for MMG in ground-based experiments. Previous experiments from our laboratory revealed that when lymphocytes (human peripheral blood mononuclear cells [PBMCs]) were first activated with phytohemaglutinin followed by exposure to MMG, locomotory capacity was not affected. In the present study, MMG inhibits lymphocyte locomotion in a manner similar to that observed in microgravity. Phorbol myristate acetate (PMA) treatment of PBMCs restored lost locomotory capacity by a maximum of 87%. Augmentation of cellular calcium flux with ionomycin had no restorative effect. Treatment of lymphocytes with mitomycin C prior to exposure to MMG, followed by PMA, restored locomotion to the same extent as when nonmitomycin C-treated lymphocytes were exposed to MMG (80-87%), suggesting that deoxyribonucleic acid replication is not essential for the restoration of locomotion. Thus, direct activation of protein kinase C (PKC) with PMA was effective in restoring locomotion in MMG comparable to the normal levels seen in Ig cultures. Therefore, in MMG, lymphocyte calcium signaling pathways were functional, with defects occurring at either the level of PKC or upstream of PKC.

  13. The Chernobyl trace in the peripheral blood lymphocytes of children living on the territories contaminated with radionuclides

    International Nuclear Information System (INIS)

    Lymphocytes were characterized by cytogenetic, cytochemical and immune phenotype parameters. The stratification of the children population was demonstrated: in lymphocytes of children living on more contaminated territories (over 15 Ci/square km) radiation-induced aberrations are often, and judging by environment-dependent cytochemical lymphocyte markers, these children have a higher risk of the possible foreseen accident consequences. 5.5 per cent of children-residents of Krasnogorsk district have accumulated inside their bodies dangerous amounts of cesium 137, producing additional internal irradiation at annual dose of over 1 mZv. The majority of these so called 'accumulator' children live on the territories where soil contamination with 137Cs exceeds 15 Ci/square km; (and even 40 Ci/square km). Significantly more radiation-induced chromosome aberrations, decreased absolute lymphocytes number (CD2+, CD4+ subsets also decreased), and significantly lower number of lymphocytes with point nonspecific esterase (the marker of mature T-lymphocytes) were observed in these 'accumulator' children. While analyzing cytochemical lymphocytograms in 1994-1995 we revealed some unfavorable trends implying probable enhancement of thyroid cancer and other chronic pathologies against the background of weakened community

  14. Serine leucocyte proteinase inhibitor-treated monocyte inhibits human CD4(+) lymphocyte proliferation.

    Science.gov (United States)

    Guerrieri, Diego; Tateosian, Nancy L; Maffía, Paulo C; Reiteri, Romina M; Amiano, Nicolás O; Costa, María J; Villalonga, Ximena; Sanchez, Mercedes L; Estein, Silvia M; Garcia, Verónica E; Sallenave, Jean-Michel; Chuluyan, Héctor E

    2011-08-01

    Serine leucocyte proteinase inhibitor (SLPI) is the main serine proteinase inhibitor produced by epithelial cells and has been shown to be a pleiotropic molecule with anti-inflammatory and microbicidal activities. However, the role of SLPI on the adaptive immune response is not well established. Therefore, we evaluated the effect of SLPI on lymphocyte proliferation and cytokine production. Human peripheral blood mononuclear cells (PBMC) were treated with mitogens plus SLPI and proliferation was assessed by [(3) H]thymidine uptake. The SLPI decreased the lymphocyte proliferation induced by interleukin-2 (IL-2) or OKT3 monoclonal antibodies in a dose-dependent manner. Inhibition was not observed when depleting monocytes from the PBMC and it was restored by adding monocytes and SLPI. SLPI-treated monocyte slightly decreased MHC II and increased CD18 expression, and secreted greater amounts of IL-4, IL-6 and IL-10 in the cell culture supernatants. SLPI-treated monocyte culture supernatant inhibited the CD4(+) lymphocyte proliferation but did not affect the proliferation of CD8(+) cells. Moreover, IL-2 increased T-bet expression and the presence of SLPI significantly decreased it. Finally, SLPI-treated monocyte culture supernatant dramatically decreased interferon-γ but increased IL-4, IL-6 and IL-10 in the presence of IL-2-treated T cells. Our results demonstrate that SLPI target monocytes, which in turn inhibit CD4 lymphocyte proliferation and T helper type 1 cytokine secretion. Overall, these results suggest that SLPI is an alarm protein that modulates not only the innate immune response but also the adaptive immune response. PMID:21574992

  15. Serine leucocyte proteinase inhibitor-treated monocyte inhibits human CD4+ lymphocyte proliferation

    Science.gov (United States)

    Guerrieri, Diego; Tateosian, Nancy L; Maffía, Paulo C; Reiteri, Romina M; Amiano, Nicolás O; Costa, María J; Villalonga, Ximena; Sanchez, Mercedes L; Estein, Silvia M; Garcia, Verónica E; Sallenave, Jean-Michel; Chuluyan, Héctor E

    2011-01-01

    Serine leucocyte proteinase inhibitor (SLPI) is the main serine proteinase inhibitor produced by epithelial cells and has been shown to be a pleiotropic molecule with anti-inflammatory and microbicidal activities. However, the role of SLPI on the adaptive immune response is not well established. Therefore, we evaluated the effect of SLPI on lymphocyte proliferation and cytokine production. Human peripheral blood mononuclear cells (PBMC) were treated with mitogens plus SLPI and proliferation was assessed by [3H]thymidine uptake. The SLPI decreased the lymphocyte proliferation induced by interleukin-2 (IL-2) or OKT3 monoclonal antibodies in a dose-dependent manner. Inhibition was not observed when depleting monocytes from the PBMC and it was restored by adding monocytes and SLPI. SLPI-treated monocyte slightly decreased MHC II and increased CD18 expression, and secreted greater amounts of IL-4, IL-6 and IL-10 in the cell culture supernatants. SLPI-treated monocyte culture supernatant inhibited the CD4+ lymphocyte proliferation but did not affect the proliferation of CD8+ cells. Moreover, IL-2 increased T-bet expression and the presence of SLPI significantly decreased it. Finally, SLPI-treated monocyte culture supernatant dramatically decreased interferon-γ but increased IL-4, IL-6 and IL-10 in the presence of IL-2-treated T cells. Our results demonstrate that SLPI target monocytes, which in turn inhibit CD4 lymphocyte proliferation and T helper type 1 cytokine secretion. Overall, these results suggest that SLPI is an alarm protein that modulates not only the innate immune response but also the adaptive immune response. PMID:21574992

  16. Metal ion levels and lymphocyte counts

    DEFF Research Database (Denmark)

    Penny, Jeannette Ø; Varmarken, Jens-Erik; Ovesen, Ole;

    2013-01-01

    BACKGROUND AND PURPOSE: Wear particles from metal-on-metal arthroplasties are under suspicion for adverse effects both locally and systemically, and the DePuy ASR Hip Resurfacing System (RHA) has above-average failure rates. We compared lymphocyte counts in RHA and total hip arthroplasty (THA) and...... investigated whether cobalt and chromium ions affected the lymphocyte counts. METHOD: In a randomized controlled trial, we followed 19 RHA patients and 19 THA patients. Lymphocyte subsets and chromium and cobalt ion concentrations were measured at baseline, at 8 weeks, at 6 months, and at 1 and 2 years....... RESULTS: The T-lymphocyte counts for both implant types declined over the 2-year period. This decline was statistically significant for CD3(+)CD8(+) in the THA group, with a regression coefficient of -0.04 × 10(9)cells/year (95% CI: -0.08 to -0.01). Regression analysis indicated a depressive effect of...

  17. Cancer Statistics: Acute Lymphocytic Leukemia (ALL)

    Science.gov (United States)

    ... population data for older age groups are available. Statistics at a Glance Show More At a Glance ... acute lymphocytic leukemia in the United States. Survival Statistics Show More How Many People Survive 5 Years ...

  18. C1-esterase inhibitor blocks T lymphocyte proliferation and cytotoxic T lymphocyte generation in vitro

    DEFF Research Database (Denmark)

    Nissen, Mogens Holst; Bregenholt, S; Nording, J A;

    1998-01-01

    beta2m in nanomolar amounts to a one-way allogenic mixed lymphocyte culture (MLC) increased the endogenous production of IL-2 and the generation of allo-specific cytotoxic T lymphocytes. C1-inh was purified from fresh human plasma and added to human or murine MLC and mitogen-stimulated lymphocyte...... cultures grown in the presence of complement-inactivated serum. Read-outs were cell proliferation, lymphokine production and development of T cell-mediated cytotoxicity. We found that addition of C1-inh to MLC and mitogen-exposed murine and human lymphocyte cultures inhibited proliferation, the development...

  19. LYMPHOCYTE PHENOTYPE IN PATIENTS WITH SKIN MELANOMA AFTER IMMUNOTHERAPY OF ACTIVATED LYMPHOCYTES

    Directory of Open Access Journals (Sweden)

    E. V. Abakushina

    2015-01-01

    Full Text Available The major medical problem in the treatment of skin melanoma is improvement methods of treatment, increasing their effectiveness and safety. In this study, adoptive immunotherapy, using lymphocytes activated in vitro, was performed in 15 patients with metastatic melanoma. Evaluated the phenotype of peripheral blood lymphocytes and activation markers (HLA-DR, CD25, CD314, CD38, CD69 before and 3-4 weeks after immunotherapy. It is shown that for these patients is characterized by increasing the number of CD25+ and Treg lymphocytes in the bloodstream, which has not changed after immunotherapy. Adoptive immunotherapy in combination with chemotherapy resulted in a decrease of absolute number of lymphocyte, B- and T-lymphocytes, T helper cells, NKT-cells, CD314+ lymphocytes, CD38+ lymphocytes and immature T-lymphocytes (CD3+CD38+ (р < 0,05. However, there was a positive dynamic to increase the percentage of NK-cells to 32% and CD69+NK-cells to 21% and significant increase in expression of HLA-DR on all lymphocytes (p < 0.05. Adoptive immunotherapy characterized by the absence of side effects and can be recommended as accompanying to basic radiation and chemotherapy.

  20. IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer

    OpenAIRE

    Abiko, K; Matsumura, N; Hamanishi, J; Horikawa, N.(Nagoya University, Nagoya, 464, Japan); Murakami, R; K. Yamaguchi; Yoshioka, Y; Baba, T; Konishi, I; Mandai, M

    2015-01-01

    Background: PD-L1 (programmed cell death 1 ligand 1) on tumour cells suppresses host immunity through binding to its receptor PD-1 on lymphocytes, and promotes peritoneal dissemination in mouse models of ovarian cancer. However, how PD-L1 expression is regulated in ovarian cancer microenvironment remains unclear. Methods: The number of CD8-positive lymphocytes and PD-L1 expression in tumour cells was assessed in ovarian cancer clinical samples. PD-L1 expression and tumour progression in mouse...

  1. Changes in T lymphocyte subsets after severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Yulu Miao; Mingxia Zhang; Yulin Nie; Wan Zhao; Bin Huang; Zhengming Jiang; Shaoxiong Yu; Zhibin Huang; Hongjin Fu

    2007-01-01

    BACKGROUND: Besides local changes of cranial parenchymal cells, hemorrhage, etc., severe traumatic brain injuries also cause the changes of total body fluid and various functions, and the changes of lymphocytes and T lymphocyte subsets should be paid more attention to.OBJECTIVE: To reveal the changing laws of T lymphocyte subsets after severe traumatic brain injury, and compare with mild to moderate brain injury.DESIGN: A comparative observation.SETTINGS: Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City;Central Laboratory of Shenzhen Hospital of Prevention and Cure for Chronic Disease.PARTICIPANTS: All the subjects were selected from the Department of Neurosurgery, Longgang District Buji People's Hospital of Shenzhen City from August 2002 to August 2005. Thirty patients with severe brain injury, whose Glasgow coma score (GCS) was ≤ 8 points, were taken as the experimental group, including 21 males and 9 females, aging 16 - 62 years. Meanwhile, 30 patients with mild traumatic brain injury were taken as the control group (GCS ranged 14 - 15 points), including 18 males and 12 females, aging 15 - 58 years. All the subjects were in admission at 6 hours after injury, without disease of major organs before injury.Informed consents were obtained from all the patients or their relatives.conditions of pulmonaryinfections were observed at 4 days after injury. The differences of measurement data were compared with the t test.MAIN OUTCOME MEASURES: Changes of T lymphocytes subsets at 1 - 14 days after severe and mild or moderate traumatic injury.RESULTS: Finally, 28 and 25 patients with mild to moderate traumatic brain injury, whereas 25 and 21 patients with severe traumatic brain injury were analyzed at 7 and 14 days respectively, and the missed ones CD3, CD4, CD8, CD4/CD8 began to decrease, whereas CD8 increased in the experimental group, which were very significantly different from those in the control group (t =2.77 - 3.26, P < 0

  2. Integrated Circuit Immunity

    Science.gov (United States)

    Sketoe, J. G.; Clark, Anthony

    2000-01-01

    This paper presents a DOD E3 program overview on integrated circuit immunity. The topics include: 1) EMI Immunity Testing; 2) Threshold Definition; 3) Bias Tee Function; 4) Bias Tee Calibration Set-Up; 5) EDM Test Figure; 6) EMI Immunity Levels; 7) NAND vs. and Gate Immunity; 8) TTL vs. LS Immunity Levels; 9) TP vs. OC Immunity Levels; 10) 7805 Volt Reg Immunity; and 11) Seventies Chip Set. This paper is presented in viewgraph form.

  3. [The cellular immunity indices of patients with malignant melanoma using the viral immunomodulator rigvir].

    Science.gov (United States)

    Glinkina, L S; Bruvere, R Zh; Venskus, D R; Garklava, R R; Muceniece, A J

    1992-01-01

    The effect of rigvir, an immunomodulator of the viral origin, on cell-mediated immunity was studied in patients with skin malignant melanoma. Rosette formation and monoclonal antibody techniques were used to measure blood immunocompetent cell levels in patients with the above pathology, cases of benign skin tumors and healthy subjects. Rigvir was shown to influence natural resistance by raising blood monocyte and large granule-containing lymphocyte levels. It potentiated recruitment of pre-T-lymphocytes and young active T-lymphocytes to the peripheral blood. PMID:1300752

  4. Lymphocytic hypophysitis and hypothalamitis - a case report

    International Nuclear Information System (INIS)

    Lymphocytic hypophysitis is an unusual disorder that nearly exclusively affects women. We present a case of 69 year-old female patient who developed the symptoms of diabetes insipidus and partial insufficiency of the anterior pituitary gland. Magnetic resonance imaging of the brain revealed a mass involving the sella and suprasellar region. After exclusion of other causes of infiltrate in this region and due to evident reaction to glucocorticoid treatment the diagnosis of lymphocytic hypophisitis and hypothalamitis was established. (author)

  5. Lymphocyte dysfunction in congenital hypoplastic anemia.

    OpenAIRE

    Finlay, J. L.; Shahidi, N T; Horowitz, S; Borcherding, W; Hong, R

    1982-01-01

    Congenital hypoplastic anemia (Diamond-Blackfan syndrome) is thought to involve the erythropoietic cell line alone. In this study, the evaluation of lymphocyte function in five patients with this syndrome revealed a number of abnormalities. Peripheral blood T lymphocyte percentages as assessed by monoclonal antibodies were decreased in three patients. T-helper/T-suppressor cell (OKT4:OKT8) ratios were almost unity in four of the five patients. We usually find a ratio of 2:1 in normal populati...

  6. Cellular immune responses of BALB/c mice induced by intramuscular injection of PRRSV-ORF5 DNA vaccine with different doses

    Institute of Scientific and Technical Information of China (English)

    CHENG Anchun; WANG Mingshu; CHEN Xiwen; XINI Nigen; DOU Wenbo; LI Xuemei; LIU Wumei; WANG Gang; ZHANG Pingying

    2007-01-01

    BALB/c mice were immunized with 50 μg,100 μg,200 μg of pcDNA-PRRSV-ORF5 DNA vaccine respectively by intramuscular injection,with PBS and pcDNA3.1(+)as controls.Fluorescence activated cell Sorter (FACS)was used to detect the number of CD4+ and CD8+T-lymphocytes.T-lymphocyte proliferation test was used to detect proliferation of the T-lymphocyte cells in peripheral blood lymphocytes of mice vaccinated with pcDNA-PRRSV-ORF5 DNA vaccine.The results showed that the difference in ConA response to T-lymphocytes in blood was highly significant between all experimental groups and the control group(P<0.01).The number of CD4+T-lymphocytes in experimental groups was significantly higher than that of the control group 7d after vaccination.The number of CD8+ T-lymphocytes in the experimental groups was higher than that of the control group 28 d after vaccination.Mice immunized with a higher dose(200 μg)of DNA vaccine demonstrated higher cellular immune response than those immunized with a lower dose(100 μg,50 μg)of DNA vaccine.The results demonstrated that pcDNA-PRRSV-ORF5 DNA vaccine could induce a good cellular immune response which may be dose-dependent.

  7. Potassium currents inhibition by gambierol analogs prevents human T lymphocyte activation.

    Science.gov (United States)

    Rubiolo, J A; Vale, C; Martín, V; Fuwa, H; Sasaki, M; Botana, L M

    2015-07-01

    Gambierol is a marine polycyclic ether toxin, produced along with ciguatoxin congeners by the dinoflagellate Gambierdiscus toxicus. We have recently reported that two truncated skeletal analogs of gambierol comprising the EFGH- and BCDEFGH-rings of the parent compound showed similar potency to gambierol on voltage-gated potassium channels (Kv) inhibition in neurons. Gambierol and its truncated analogs share the main crucial elements for biological activity, which are the C28=C29 double bond within the H-ring and the unsaturated side chain. Since Kv channels are critical for the regulation of calcium signaling, proliferation, secretion and migration in human T lymphocytes, we evaluated the activity of both the tetracyclic and heptacyclic analogs of gambierol on potassium currents in resting T lymphocyte and their effects on interleukin-2 (IL-2) release and gene expression in activated T lymphocytes. The results presented in this work clearly demonstrate that both truncated analogs of gambierol inhibit Kv channels present in resting T lymphocytes (Kv1.3) and prevented lymphocyte activation by concanavalin A. The main effects of the heptacyclic and tetracyclic analogs of gambierol in human T cells are: (1) inhibition of potassium channels in resting and concanavalin-activated T cells in the nanomolar range, (2) inhibition of IL-2 release from concanavalin-activated T cells and (3) negatively affect the expression of genes involved in cell proliferation and immune response observed in concanavalin-activated lymphocytes. These results together with the lack of toxicity in this cellular model, indicates that both analogs of gambierol have additional potential for the development of therapeutic tools in autoimmune diseases. PMID:25155189

  8. Perfil fenotípico de linfócitos periféricos de bovinos de raças européias Phenotypic profile of peripheral blood lymphocytes from European bovines

    Directory of Open Access Journals (Sweden)

    J.F.F. Bittar

    2004-02-01

    Full Text Available The phenotypic profile of bovine lymphocytes was evaluated in 18 bovines (Bos taurus from three different breeds, being nine Holstein, six Hereford, and three Brown Swiss. All animals were free from ticks and hemoparasites, as determined after jugular vein blood sampling. The immunophenotypes of peripheral lymphocytes were evaluated by flow cytometry. Peripheral lymphocytes were exposed to bovine fluorescein-labeled monoclonal antibodies including anti-CD4, anti-CD8, and anti-purified bovine CD21 specificities. After lysing the erythrocytes with a commercial lysing solution (FACS TM , the lymphocytes were washed, fixed, and evaluated by flow cytometry. Significant differences in the phenotypic profiles of peripheral lymphocytes among all breeds were found. Holstein animals showed a lower percentage of total T lymphocytes (CD4 and CD8 and higher percentage of B lymphocytes (CD21. In addition, the lymphocytes from Holstein animals showed a lower T/B ratio than the lymphocytes from Hereford animals. These results suggest the existence of different phenotypic profiles of peripheral lymphocytes from European breeds of cattle. Such differences may be related to the different pattern of immune response described for these breeds in the literature and may account to varying disease resistance among breeds.

  9. Chemotaxis of large granular lymphocytes

    International Nuclear Information System (INIS)

    The hypothesis that large granular lymphocytes (LGL) are capable of directed locomotion (chemotaxis) was tested. A population of LGL isolated from discontinuous Percoll gradients migrated along concentration gradients of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), casein, and C5a, well known chemoattractants for polymorphonuclear leukocytes and monocytes, as well as interferon-β and colony-stimulating factor. Interleukin 2, tuftsin, platelet-derived growth factor, and fibronectin were inactive. Migratory responses were greater in Percoll fractions with the highest lytic activity and HNK-1+ cells. The chemotactic response to f-MLP, casein, and C5a was always greater when the chemoattractant was present in greater concentration in the lower compartment of the Boyden chamber. Optimum chemotaxis was observed after a 1 hr incubation that made use of 12 μm nitrocellulose filters. LGL exhibited a high degree of nondirected locomotion when allowed to migrate for longer periods (> 2 hr), and when cultured in vitro for 24 to 72 hr in the presence or absence of IL 2 containing phytohemagluttinin-conditioned medium. LGL chemotaxis to f-MLP could be inhibited in a dose-dependent manner by the inactive structural analog CBZ-phe-met, and the RNK tumor line specifically bound f-ML(3H)P, suggesting that LGL bear receptors for the chemotactic peptide

  10. Effects of bestatin on the host immunity in patients treated for urogenital cancer

    International Nuclear Information System (INIS)

    To examine effects of bestatin on the host immunity of patients with urogenital cancer, 54 patients were randomized into 2 groups: bestatin treated and controls. In each group, the patients were divided into 2 subgroups: one which received basic treatment expected to greatly affect host immunity ('invasive treatment') while the other one received other types of basic treatment ('non-invasive treatment'). Peripheral lymphocyte, OKT 4/8 ratio and purified protein derivative (PPD) skin reaction were used as immunological markers. There were significant differences in the 'invasive' treatment group between bestatin treated patients and controls concerning lymphocyte counts and PPD skin reactions and in the 'non-invasive' group concerning lymphocyte counts and OKT 4/8 ratios. These results suggest that bestatin may potentiate host immunity in patients with urogenital cancer. Further studies on larger materials are, however, needed before more definite conclusions can be drawn. (orig.)

  11. Changes in lymphocyte populations in suckling piglets during primary infections with Isospora suis.

    Science.gov (United States)

    Worliczek, H L; Buggelsheim, M; Alexandrowicz, R; Witter, K; Schmidt, P; Gerner, W; Saalmüller, A; Joachim, A

    2010-04-01

    Isospora suis, a common intestinal parasite of piglets, causes neonatal porcine coccidiosis, which results in reduced and uneven weaning weights and economic losses in pig production. Nevertheless, there are no detailed studies available on the immune response to I. suis. The aim of this study was to carry out phenotypical characterization of lymphocytes during primary infections on day 3 after birth. Infected and noninfected piglets were investigated between days 7 and 16 after birth. Lymphocytes from the blood, spleen and mesenteric lymph nodes (flow cytometry) and of the jejunal mucosa (immunohistochemistry) were analysed. A decrease in T cells, especially with the phenotype of resting T-helper cells, T-cell receptor-gammadelta-T cells, and regulatory T cells in the blood, spleen and mesenteric lymph nodes was noticeable. An increase in cells with the phenotype of natural killer cells in the spleen of infected animals was found, and the subset of TcR-gammadelta-T cells was strongly increased in the gut mucosa. Our findings suggest an accelerated migration of those cells into the gut. This study provides a strong indication for the involvement of adaptive and innate immune response mechanisms in the primary immune response to I. suis, especially of TcR-gammadelta-T cells as a linkage between innate and adaptive immunity. PMID:20398223

  12. The blockade of immune checkpoints in cancer immunotherapy

    Science.gov (United States)

    Pardoll, Drew M.

    2016-01-01

    Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand–receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses. PMID:22437870

  13. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jeroen Pouwels

    2013-11-01

    Full Text Available SHARPIN-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization, and migration. We found that SHARPIN localizes to the trailing edges (uropods of both mouse and human chemokine-activated lymphocytes migrating on intercellular adhesion molecule-1 (ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration, and uropod defects in SHARPIN-deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically, we show that SHARPIN interacts directly with lymphocyte-function-associated antigen-1 (LFA-1, a leukocyte counterreceptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus, SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells.

  14. Hypertrophic gastropathy with gastric adenocarcinoma: Menetrier's disease and lymphocytic gastritis?

    OpenAIRE

    Mosnier, J F; Flejou, J F; Amouyal, G; Gayet, B; Molas, G.; Henin, D; Potet, F

    1991-01-01

    Lymphocytic gastritis is a form of gastric inflammation characterised by a pronounced increase in lymphocytes in gastric surface and foveolar epithelium. Lymphocytic gastritis is often associated with endoscopic evidence of 'varioliform gastritis'. Lymphocytic gastritis has recently been reported to be associated with other forms of hypertrophic gastropathies. We present a case of hypertrophic gastropathy with gastric adenocarcinoma, with both Menetrier's disease and lymphocyte gastritis. Imm...

  15. A mechanism for trauma induced muscle wasting and immune dysfunction

    Science.gov (United States)

    Madihally, S.; Toner, M.; Yarmush, M.; Mitchell, R.

    A diverse physiological conditions lead to a hypercatabolic state marked by the loss of proteins, primarily derived from skeletal muscle. The sustained loss of proteins results in loss of muscle mass and strength, poor healing, and long-term hospitalization. These problems are further compounded by the deterioration of immunity to infection which is a leading cause of morbidity and mortality of traumatic patients. In an attempt to understand the signal propagation mechanism(s), we tested the role of Interferon-? (IFN-? ) in an animal burn injury model; IFN-? is best conceptualized as a macrophage activating protein and known to modulate a variety of intracellular processes potentially relevant to muscle wasting and immune dysfunction. Mice congenitally -deficient in IFN-? , and IFN-? -Receptor, and wild type (WT) animals treated with IFN-? neutralizing antibody received either a 20% total body surface area burn or a control sham treatment. At days 1, 2, and 7 following treatment, skeletal muscle, peripheral blood, and spleen were harvested from both groups. Overall body weight, protein turnovers, changes in the lymphocyte subpopulations and alterations in the major histocompatibility complex I expression (MHC I) and proliferation capacity of lymphocytes was measured using mixed lymphocyte reaction (MLR). These results indicate that we can prevent both muscle wasting and immune dysfunction. Based on these observations and our previous other animal model results (using insulin therapy), a novel mechanism of interactions leading to muscle wasting and immune dysfunction will be discussed. Further, implications of these findings on future research and clinical therapies will be discussed in detail.

  16. Immune thrombocytopenia.

    Science.gov (United States)

    Maher, George M

    2014-10-01

    Immune thrombocytopenia (ITP) in children is a relatively uncommon and generally benign condition presenting as abrupt onset of bruising, petechiae and thrombocytopenia in an otherwise healthy child due to production of anti-platelet autoantibodies. Diagnosis is largely clinical and laboratory investigation should be kept to a minimum. Indications for treatment have not been standardized and include bleeding, parental anxiety and quality of life. Multiple treatments are available that have been proven to increase the platelet count; the most commonly employed include IVIG, steroids and WinRho (anti-D). Intracranial hemorrhage is the most serious potential complication but is extremely rare and splenectomy is reserved for chronically symptomatic patients who have not responded to other modalities. Identification of molecular targets may be a promising avenue for future research. PMID:25423768

  17. Interleukin-2/Anti-Interleukin-2 Immune Complex Expands Regulatory T Cells and Reduces Angiotensin II-Induced Aortic Stiffening

    OpenAIRE

    Beenish Majeed; Supannikar Tawinwung; Lance S. Eberson; SECOMB, TIMOTHY W.; Nicolas Larmonier; Larson, Douglas F.

    2014-01-01

    Adaptive immune function is implicated in the pathogenesis of vascular disease. Inhibition of T-lymphocyte function has been shown to reduce hypertension, target-organ damage, and vascular stiffness. To study the role of immune inhibitory cells, CD4+CD25+Foxp3+ regulatory T cells (Tregs), on vascular stiffness, we stimulated the proliferation of Treg lymphocytes in vivo using a novel cytokine immune complex of Interleukin-2 (IL-2) and anti-IL-2 monoclonal antibody clone JES6-1 (mAbCD25). Thre...

  18. Effect of regular circus physical exercises on lymphocytes in overweight children.

    Directory of Open Access Journals (Sweden)

    Cesar Miguel Momesso dos Santos

    Full Text Available Obesity associated with a sedentary lifestyle can lead to changes in the immune system balance resulting in the development of inflammatory diseases. The aim of this study was to compare lymphocyte activation mechanisms between overweight children practicing regular circus physical exercises with non-exercised children. The study comprised 60 pubescent children randomly divided into 4 groups: Overweight Children (OWC (10.67 ± 0.22 years old, Overweight Exercised Children (OWE (10.00 ± 0.41 years old, Eutrophic Children (EC (11.00 ± 0.29 years old and Eutrophic Exercised Children (EE (10.60 ± 0.29 years old. OWE and EE groups practiced circus activities twice a week, for 4.3 ± 0.5 and 4.4 ± 0.5 months, respectively. Percentage of T regulatory cells (Treg and the expression of CD95 and CD25 in CD4+ lymphocytes were evaluated by flow cytometry. Lymphocyte proliferation capacity was measured by [14C]-thymidine incorporation and mRNA expression of IL-35, TGF-beta, IL-2 and IL-10 by real-time PCR. Lymphocyte proliferation was higher in OWC and OWE groups compared with the EC (3509 ± 887; 2694 ± 560, and 1768 ± 208 cpm, respectively and EE (2313 ± 111 cpm groups. CD95 expression on lymphocytes was augmented in the EC (953.9 ± 101.2 and EE groups (736.7 ± 194.6 compared with the OWC (522.1 ± 125.2 and OWE groups (551.6 ± 144.5. CTLA-4 expression was also lower in the OWC and OWE groups compared with the EC and EE groups. Percentage of Treg, IL-35, and IL-10 mRNA expression were lower in the OWC and OWE groups compared with the EC and EE groups. In conclusion, overweight children present altered immune system balance characterized by elevated lymphocyte proliferation due to a decrease in T regulatory cell percentage. These effects were partially reverted by moderate physical exercise, as demonstrated by decreased lymphocyte proliferation.

  19. Inorganic arsenic represses interleukin-17A expression in human activated Th17 lymphocytes

    International Nuclear Information System (INIS)

    Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to treat patients suffering from acute promyelocytic leukemia. Recently, experimental studies have clearly demonstrated that this metalloid can also cure lymphoproliferative and/or pro-inflammatory syndromes in different murine models of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a central role in development of these diseases, in mice and humans, especially by secreting the potent pro-inflammatory cytokine interferon-γ and IL-17A, respectively. As(III) impairs basic functions of human T cells but its ability to modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes is unknown. In the present study, we demonstrate that As(III), used at concentrations clinically achievable in plasma of patients, has no effect on the secretion of interferon-γ from Th1 cells but almost totally blocks the expression and the release of IL-17A from human Th17 lymphocytes co-stimulated for five days with anti-CD3 and anti-CD28 antibodies, in the presence of differentiating cytokines. In addition, As(III) specifically reduces mRNA levels of the retinoic-related orphan receptor (ROR)C gene which encodes RORγt, a key transcription factor controlling optimal IL-17 expression in fully differentiated Th17 cells. The metalloid also blocks initial expression of IL-17 gene induced by the co-stimulation, probably in part by impairing activation of the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III) represses expression of the major pro-inflammatory cytokine IL-17A produced by human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to treat inflammatory immune-mediated diseases in humans. -- Highlights: ► Arsenic inhibits secretion of IL-17A from human naïve and memory Th17 lymphocytes. ► Arsenic represses early expression of IL-17A gene in human activated T lymphocytes. ► Arsenic interferes with activation of

  20. Inorganic arsenic represses interleukin-17A expression in human activated Th17 lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Morzadec, Claudie; Macoch, Mélinda; Robineau, Marc; Sparfel, Lydie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

    2012-08-01

    Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to treat patients suffering from acute promyelocytic leukemia. Recently, experimental studies have clearly demonstrated that this metalloid can also cure lymphoproliferative and/or pro-inflammatory syndromes in different murine models of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a central role in development of these diseases, in mice and humans, especially by secreting the potent pro-inflammatory cytokine interferon-γ and IL-17A, respectively. As(III) impairs basic functions of human T cells but its ability to modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes is unknown. In the present study, we demonstrate that As(III), used at concentrations clinically achievable in plasma of patients, has no effect on the secretion of interferon-γ from Th1 cells but almost totally blocks the expression and the release of IL-17A from human Th17 lymphocytes co-stimulated for five days with anti-CD3 and anti-CD28 antibodies, in the presence of differentiating cytokines. In addition, As(III) specifically reduces mRNA levels of the retinoic-related orphan receptor (ROR)C gene which encodes RORγt, a key transcription factor controlling optimal IL-17 expression in fully differentiated Th17 cells. The metalloid also blocks initial expression of IL-17 gene induced by the co-stimulation, probably in part by impairing activation of the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III) represses expression of the major pro-inflammatory cytokine IL-17A produced by human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to treat inflammatory immune-mediated diseases in humans. -- Highlights: ► Arsenic inhibits secretion of IL-17A from human naïve and memory Th17 lymphocytes. ► Arsenic represses early expression of IL-17A gene in human activated T lymphocytes. ► Arsenic interferes with activation of

  1. Balancing immune protection and immune pathology by CD8+ T cell responses to influenza infection

    Directory of Open Access Journals (Sweden)

    Susu eDuan

    2016-02-01

    Full Text Available Influenza A virus (IAV is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL-mediated immunity contributes to clearance of virus-infected cells; CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, their cytotoxicity, and the effects of produced pro-inflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL anti-viral immunity from those necessary to restrain CTL-mediated nonspecific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity.

  2. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  3. Lymphocyte radiosensitivity in multiple sclerosis patients

    International Nuclear Information System (INIS)

    The purpose of the study was to characterize the radiosensitivity of the peripheral blood lymphocytes from Secondary Progressive Multiple Sclerosis (MS) patients in order to get insights in the ability of these cells to deal with DNA damage. Genetic defects in the repair mechanisms of DNA have not been systematically observed in MS but they have been found in other autoimmune diseases such as lupus erythematosus and rheumatoid arthritis, as well as in several disorders of the nervous system. Up to now investigations into cellular radio-sensitivity in MS patients comparative to healthy controls have yielded contradictory results. The following methods were used: The chromosomal radiosensitivity of lymphocytes was assessed after in vitro 2 Gy gamma irradiation in G0 phase of the cell cycle, using the micronucleus (MN) assay. The MN assay was performed on whole blood cultures, separated PBMC cultures, and CD4+ and CD8+ subsets of T lymphocytes from blood samples of the MS (n=26) patients and on concurrent samples of healthy individuals (n=22). The results obtained are summarized as follows: The spontaneous MN induction was found significantly higher in whole blood and PBMC cultures for MS patients comparatively to controls. The differences had statistical significance for total lymphocyte population and also for separated CD4+ and CD8+ lymphocytes. No correlation has been observed between the spontaneous MN yield and illness duration for the group of MS patients. No difference in radiosensitivity was observed between patients and controls after 2 Gy irradiation of whole blood. In irradiated PBMC cultures, a slightly lower induction of MN was observed in the case of MS patients. For the MS patients, lymphocyte radiosensitivity was significantly higher in whole blood culture environment compared to PBMC culture environment. The CD4+ lymphocyte subset from MS patients was significantly less radiosensitive compared to healthy controls. On the other hand, CD8+ lymphocytes

  4. Mosaic vaccines elicit CD8+ T cell responses in monkeys that confer immune coverage of diverse HIV strains

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Will [Los Alamos National Laboratory; Korber, Bette [Los Alamos National Laboratory

    2009-01-01

    Creation of a successful HIV vaccine will require the development of a strategy to generate cellular immunity with sufficient cross-clade breadth to deal with the extreme genetic diversity of the virus. Polyvalent mosaic immunogens derived from in silica recombination of natural strains of HIV are designed to induce cellular immune responses that maximally cover the sequence diversity of circulating virus isolates. Immunization of rhesus monkeys with plasmid DNA and recombinant vaccinia virus vaccine constructs expressing either consensus immunogens or polyvalent mosaic immunogens elicited a CD4+ T lymphocyte-biased response with comparably broad epitope-specific total T lymphocyte specificities. However, immunization with the mosaic immunogens induced HIV-specific CD8+ T lymphocyte responses with markedly greater depth and breadth. Therefore, the use of polyvalent mosaic immunogens is a promising strategy for a global vaccine for HIV.

  5. IMMUNITY AND INFECTION IN WOMEN WITH HYPERPLASTIC STATES OF IMMUNE SYSTEM

    Directory of Open Access Journals (Sweden)

    A. A. Lukach

    2008-01-01

    Full Text Available Abstract. One hundred and ninety-nine patients with hyperplastic processes of reproductive system were examined, and 131 (66.16% of them were found to be infected with Chlamydia or Ureaplasma. The mean age of female patients was 42,7±1,35 years. Different infectious agents (e.g. Chlamydia trachomatis, Ureaplasma urealiticum, Mycoplasma hominis were identified in cervical canal of uterine cervix and surgical specimens (biopsy samples of excised myoma, adenomyosis or endometrial hyperplasia. The infected patients were found to have decreased monocytes and neutrophils in blood counts, lower phagocytic activity of monocytes and neutrophils, and decreased bactericidal activity of leukocytes. Other findings included lower CD20+, CD8+ and rFAS CD 95 lymphocytes. Assessment of cytokine-synthesizing activity of CD3+ lymphocytes showed a decrease in both spontaneous and stimulated response (р < 0,001. A weakest spontaneous and stimulated response was found in CD3+/IL-4+ lymphocytes. Analysis of results obtained shows systemic immune disorders and impaired cytokine-synthesizing activity of CD3+ lymphocytes correlating with infection factors in the women with hyperplastic processes of reproductive system. (Med. Immunol., 2008, vol. 10, N 2-3, pp 223-228.

  6. Effects of Anti-CD45RB Monoclonal Antibody for T Lymphocyte Subsets in Mice Heart Transplantation Model.

    Science.gov (United States)

    Deng, C-Y; Wang, X-F; Qi, H; Li, F-R

    2016-08-01

    Anti-CD45RB monoclonal antibody (anti-CD45RBmAb), as a new immune tolerance inducer, may inhibit T cell proliferation and induce immune tolerance through competitive combination with CD45RB on the T cell surface, which blocks the conduction of activation signals. However, how anti-CD45RBmAb plays its role on T lymphocyte subsets during immunosuppression remains unclear. In this work, we investigate the effects of anti-CD45RBmAb on CD3(+) T lymphocyte both in vitro and in allogeneic heart transplant model in vivo. Interestingly, anti-CD45RBmAb could inhibit the proliferation of T cells, promote the transformation of T lymphocyte to Treg and Th2 cells, suppress the transformation to Th17 and Th1 cells, increase the number of Ts cells, decrease the number of Tm cells and thus play a role in immune inhibition and induction of immune tolerance. PMID:27146476

  7. Lymphocyte Proliferation Response to S Antigen in Patients with Uveitis and Optic Neuritis

    Institute of Scientific and Technical Information of China (English)

    PeixianRen; XiuzhenYan

    1995-01-01

    Purpose:To evaluate the autoimmunity which may play a major role in the etiolo-gy of certain forms of uveitis and optic neuritis.Methods:lymphocyte proliferation response to retinal soluble antigen in vitro by gy of certain forms of uveitis and optic neuritis.Methods:Lymphocyte proliferation response toretinal soluble antigen in vitro by incoperation3H-thymidine withDNA was tested in 115patients with anterior u-veitis,posterior/pan-uveitis,optic neuritis,and 50volunteers with unrelated diseases such as congenital ptosis,strabismus,or completely healthy persons as control.Results:The positive rate of lymphocyte stimulation was34%(18/53)in anteri-or uveitis,41.5%(17/41)in posterior/pan-uveitis,and57.1%(12/21)in optic euritis,The results in the experimental groups were significantly different from those of the control group(x2=14.76,P<0.05,x2=19.14P<0.005,x2=26.38,P<0.005,respectively).Conclusion:The autoimmunity plays a role in the patogenesis in certain forms of uveitis and optic neuritis,Such immune responses may be secondary to the expo-sition or release of retinal antigens by various causes,leading to activation or augmentation of meager or low-affinity S antigen specific lymphocytes which may preexist in the circulation and starting the pathogenic autoimmune process.Eye Science 1995;11:120-123.

  8. Signaling via the CD2 receptor enhances HTLV-1 replication in T lymphocytes.

    Science.gov (United States)

    Guyot, D J; Newbound, G C; Lairmore, M D

    1997-07-21

    Human T lymphotropic virus type 1 (HTLV-1) is considered the etiologic agent of adult T cell leukemia/lymphoma and several chronic progressive immune-mediated diseases. Approximately 1-4% of infected individuals develop disease, generally decades following infection. Increased proviral transcription, mediated by the viral 40-kDa trans-activating protein, Tax, has been implicated in the pathogenesis of HTLV-1-associated diseases. Since the HTLV-1 promoter contains sequences responsive to cyclic AMP and protein kinase C, we hypothesized that lymphocyte activation signals initiated through the TCR/CD3 complex or CD2 receptor promote viral replication in HTLV-1-infected lymphocytes. We demonstrate that mAbs directed against the CD2, but not the CD3 receptor increase viral p24 capsid protein 1.5- to 5.7-fold in CD2/CD3+ HTLV-1-infected cell culture supernatants. Northern blot analysis demonstrated a 2.5- to 4-fold increase in all species of viral mRNA following CD2 cross-linking of OSP2/4 cells, an immortalized HTLV-1 cell line. Consistent with transcriptional regulation, reporter gene activity increased approximately 11-fold in CD2-stimulated Jurkat T cells cotransfected with a Tax-expressing plasmid and a CAT reporter gene construct under control of the HTLV-1 promoter. These data suggest a possible physiologic mechanism, whereby CD2-mediated cell adhesion and lymphocyte activation may promote viral transcription in infected lymphocytes. PMID:9234953

  9. Clonal Characteristics of Circulating B Lymphocyte Repertoire in Primary Biliary Cholangitis.

    Science.gov (United States)

    Tan, Yan-Guo; Wang, Yu-Qi; Zhang, Ming; Han, Ying-Xin; Huang, Chun-Yang; Zhang, Hai-Ping; Li, Zhuo-Min; Wu, Xiao-Lei; Wang, Xiao-Feng; Dong, Yan; Zhu, Hong-Mei; Zhu, Shi-da; Li, Hong-Mei; Li, Ning; Yan, Hui-Ping; Gao, Zu-Hua

    2016-09-01

    Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by elevated serum anti-mitochondrial Ab and lymphocyte-mediated bile duct damage. This study was designed to reveal the clonal characteristics of B lymphocyte repertoire in patients with PBC to facilitate better understanding of its pathogenesis and better management of these patients. Using high-throughput sequencing of Ig genes, we analyzed the repertoire of circulating B lymphocytes in 43 patients with PBC, and 34 age- and gender-matched healthy controls. Compared with healthy controls, PBC patients showed 1) a gain of 14 new clones and a loss of 8 clones; 2) a significant clonal expansion and increased relative IgM abundance, which corresponded with the elevated serum IgM level; 3) a significant reduction of clonal diversity and somatic hypermutations in class-switched sequences, which suggested a general immunocompromised status; 4) the reduction of clonal diversity and enhancement of clonal expansion were more obvious at the cirrhotic stage; and 5) treatment with ursodeoxycholic acid could increase the clonal diversity and reduce clonal expansion of the IgM repertoire, with no obvious effect on the somatic hypermutation level. Our data suggest that PBC is a complex autoimmune disease process with evidence of B lymphocyte clonal gains and losses, Ag-dependent ogligoclonal expansion, and a generally compromised immune reserve. This new insight into the pathogenesis of PBC opens up the prospect of studying disease-relevant B cells to better diagnose and treat this devastating disease. PMID:27430717

  10. Anergy in self-directed B lymphocytes from a statistical mechanics perspective

    CERN Document Server

    Agliari, Elena; Del Ferraro, Gino; Guerra, Francesco; Tantari, Daniele

    2012-01-01

    The ability of the adaptive immune system to discriminate between self and non-self mainly stems from the ontogenic clonal-deletion of lymphocytes expressing strong binding affinity with self-peptides. However, some self-directed lymphocytes may evade selection and still be harmless due to a mechanism called clonal anergy. As for B lymphocytes, two major explanations for anergy developed over three decades: according to "Varela theory", it stems from a proper orchestration of the whole B-repertoire, in such a way that self-reactive clones, due to intensive interactions and feed-back from other clones, display more inertia to mount a response. On the other hand, according to the `two-signal model", which has prevailed nowadays, self-reacting cells are not stimulated by helper lymphocytes and the absence of such signaling yields anergy. The first result we present, achieved through disordered statistical mechanics, shows that helper cells do not prompt the activation and proliferation of a certain sub-group of ...

  11. Cytotoxic T lymphocyte antigen-4 (CTLA-4 A49G polymorphism and autoimmune blood diseases

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    Faruk Aktürk

    2010-06-01

    Full Text Available Objective: The cytotoxic T lymphocyte associated antigen-4 (CTLA-4 is expressed on T lymphocytes, and inhibits the T-cell responses. In animal models, it has been shown that complete CTLA-4 deficiency was lethal due to massive infiltration of tissues by polyclonally proliferating lymphocytes. CTLA-4 A49G polymorphism, which has been suggested to reduce the inhibitory function of the CTLA-4 molecule, was found to be associated with various autoimmune diseases in recent studies. Material and Methods: In this study, we evaluated the frequency of CTLA-4 A49G polymorphism in 46 patients with autoimmune hemolytic anemia (AIHA, 62 patients with immune thrombocytopenic purpura (ITP, and 150 healthy individuals. Results: Allele frequencies and genotype distributions were similar in both ITP and AIHA patients compared to healthy individuals. In subgroup analysis, however, we found that in chronic lymphocytic leukemia (CLL patients with AIHA (n=4, all patients had CTLA-4 A49G polymorphism (3 had AG, 1 had GG. There was no significant statistical association between G allele and systemic lupus erythematosus (SLE or AIHA.Conclusion: These data suggest that CTLA-4 A49G polymorphism does not contribute to the pathogenesis of lymphoproliferative diseases itself, nor does it increase the risk of autoimmune complications in patients with lymphoproliferative disease.

  12. Suppression of lymphocyte proliferation by marijuana components is related to cell number and cell source

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    Klein, T.; Pross, S.; Newton, C.; Friedman, H.

    1986-03-05

    Conflicting reports have appeared concerning the effect of marijuana components on immune responsiveness. The authors have observed that the effect of cannabinoids on lymphocyte proliferation varied with both the concentration of the drug and the mitogen used. They now report that at a constant concentration of drug, the cannabinoid effect varied from no effect to suppression depending upon the number of cells in culture and the organ source of the cells. Dispersed cell suspensions of mouse lymph node, spleen, and thymus were prepared and cultured at varying cell numbers with either delta-9-tetrahydrocannabinol or 11-hydroxy-delta-9-tetrahydrocannabinol and various mitogens. Lymphocyte proliferation was analyzed by /sup 3/H-thymidine incorporation. T-lymphocyte mitogen responses in cultures containing high cell numbers were unaffected by the cannabinoids but as cell numbers were reduced a suppression of the response was observed. Furthermore, thymus cells were considerably more susceptible to cannabinoid suppression than cells from either lymph node or spleen. These results suggest that certain lymphocyte subpopulations are more sensitive to cannabinoid suppression and that in addition to drug concentration other variables such as cell number and cell source must be considered when analyzing cannabinoid effects.

  13. Suppression of lymphocyte proliferation by marijuana components is related to cell number and cell source

    International Nuclear Information System (INIS)

    Conflicting reports have appeared concerning the effect of marijuana components on immune responsiveness. The authors have observed that the effect of cannabinoids on lymphocyte proliferation varied with both the concentration of the drug and the mitogen used. They now report that at a constant concentration of drug, the cannabinoid effect varied from no effect to suppression depending upon the number of cells in culture and the organ source of the cells. Dispersed cell suspensions of mouse lymph node, spleen, and thymus were prepared and cultured at varying cell numbers with either delta-9-tetrahydrocannabinol or 11-hydroxy-delta-9-tetrahydrocannabinol and various mitogens. Lymphocyte proliferation was analyzed by 3H-thymidine incorporation. T-lymphocyte mitogen responses in cultures containing high cell numbers were unaffected by the cannabinoids but as cell numbers were reduced a suppression of the response was observed. Furthermore, thymus cells were considerably more susceptible to cannabinoid suppression than cells from either lymph node or spleen. These results suggest that certain lymphocyte subpopulations are more sensitive to cannabinoid suppression and that in addition to drug concentration other variables such as cell number and cell source must be considered when analyzing cannabinoid effects

  14. Tumor-infiltrating lymphocytes predict cutaneous melanoma survival.

    Science.gov (United States)

    Fortes, Cristina; Mastroeni, Simona; Mannooranparampil, Thomas J; Passarelli, Francesca; Zappalà, Alba; Annessi, Giorgio; Marino, Claudia; Caggiati, Alessio; Russo, Nicoletta; Michelozzi, Paola

    2015-08-01

    Understanding differences in survival across distinct subgroups of melanoma patients may help with the choice of types of therapy. Tumor-infiltrating lymphocytes (TILs) are considered a manifestation of the host immune response to tumor, but the role of TILs in melanoma mortality is controversial. The aim of this study was to investigate independent prognostic factors for melanoma mortality. We carried out a 10-year cohort study on 4133 melanoma patients from the same geographic area (Lazio) with primary cutaneous melanoma diagnosed between January 1998 and December 2008. The probability of survival was estimated using Kaplan-Meier methods and prognostic factors were evaluated by multivariate analysis (Cox proportional hazards model). The 10-year survival rate for melanoma decreased with increasing Breslow thickness (Pfor trendhazard ratio 0.32; 95% confidence interval 0.13-0.82) after controlling for sex, age, Breslow thickness, histological type, mitotic rate, and ulceration. After including lymph node status in the multivariate analysis, the protective effect of marked TILs on melanoma mortality remained (hazard ratio 0.37; 95% confidence interval 0.15-0.94). The results of this study suggest that the immune microenvironment affects melanoma survival. PMID:25933208

  15. Characterization of human γδ T lymphocytes infiltrating primary malignant melanomas.

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    Adriana Cordova

    Full Text Available T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that γδ T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating γδ T cells from 74 patients with primary melanoma. We found that γδ T cells represent the major lymphocyte population infiltrating melanoma, and both Vδ1(+ and Vδ2(+ cells are involved. The majority of melanoma-infiltrating γδ cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal γδ T cell lines obtained from tumor-infiltrating immune cells produced IFN-γ and TNF-α and were capable of killing melanoma cell lines in vitro. The cytotoxic capability of Vδ2 cell lines was further improved by pre-treatment of tumor target cells with zoledronate. Moreover, higher rate of γδ T cells isolation and percentages of Vδ2 cells correlate with early stage of development of melanoma and absence of metastasis. Altogether, our results suggest that a natural immune response mediated by γδ T lymphocytes may contribute to the immunosurveillance of melanoma.

  16. CD4+ T Lymphocytes count in sickle cell anaemia patients attending a tertiary hospital

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    Omotola Toyin Ojo

    2014-01-01

    Full Text Available Background: Sickle cell haemoglobin (HbS is the commonest abnormal haemoglobin and it has a worldwide distribution. Reports have shown that patients with sickle cell anaemia (HbSS have an increased susceptibility to infection leading to increased morbidity and mortality. Impaired leucocyte function and loss of both humoral and cell-mediated immunity are some of the mechanisms that have been reported to account for the immunocompromised state in patients with sickle cell disease. This study was carried out to determine the CD4+ T lymphocytes count in patients with sickle cell anaemia. Materials and Methods: A comparative cross-sectional study of 40 sickle cell anaemia patients in steady state (asymptomatic for at least 4 weeks attending haematology clinic and 40 age and sex-matched healthy HbA control were recruited into the study. Both HbS patients and the controls were HIV negative. The blood samples obtained were analyzed for CD4+ T cell by Flow cytometry. Results: The study found that there was no significant difference in the number of CD4+ T lymphocyte count between individuals with sickle cell anaemia and HbA (1016 ± 513 cells/μL vs 920 ± 364cells/μL. Conclusion: It is recommended that the functionality of CD4+ T lymphocyte should be considered rather than the number in further attempt to elucidate the cellular immune dysfunction in patients with sickle cell anaemia.

  17. Serum microRNAs as biomarkers of human lymphocyte activation in health and disease.

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    Paola ede Candia

    2014-02-01

    Full Text Available Induction of the adaptive immune system is evaluated mostly by assessment of serum antibody titers and T lymphocyte responses in peripheral blood, although T and B cell activation occurs in lymphoid tissues. In recent years, the release of microRNAs (miRNAs in the extra-cellular environment has been exploited to assess cell functions at distance via measurement of serum miRNAs. Also activated lymphocytes release a large amount of nano-sized vesicles (exosomes, containing miRNA, but there are still few data on whether this phenomenon is reflected in modulation of serum miRNAs. Interestingly, miRNA signatures of CD4+ T cell-derived exosomes are substantially different from intracellular miRNA signatures of the same cells. We have recently identified serum circulating miR-150 as a sensor of general lymphocyte activation and we strongly believe that the identification of miRNAs differentially released by specific CD4+ effector T cell subsets (Th1, Th2, Th17 and Treg may work as serum biomarkers of their elicitation in lymphoid tissues but also in damaged tissues, thus providing pivotal information about the nature of immune responses occurring in health and disease.

  18. Inhibition of subcutaneous growth of Ehrlich Ascites Carcinoma (EAC) tumor by post-immunization with EAC-cell gangliosides and its anti-idiotype antibody in relation to tumor angiogenesis, apoptosis, cell cycle and infiltration of CD4+, CD8+ lymphocytes, NK cells, suppressor cells and APC-cells in tumor

    International Nuclear Information System (INIS)

    Both EAC-tumor associated gangliosides and its anti-idiotype antibody inhibited growth of this tumor significantly. Immuno-histological studies with von Willebrand Factor (vWF) antibody indicated that tumor angiogenesis as determined by expression of vWF decreased in tumors of mice, post-immunized with EAC-cell gangliosides as well as its anti-idiotype antibody. Infiltration of various immune cells of the host in the tumor correlated to some extent with tumor-growth inhibition. Apoptosis study using AnnexinV-FITC and propidium iodide indicated that tumor growth inhibition in mice post-immunized with EAC-gangliosides and its anti-idiotype antibody were due to enhanced apoptosis and cell death. Cell cycle analysis by FACS indicated that EAC-cell associated gangliosides and its anti-idiotype antibody were acting both at the M2 i.e. S and M3 i.e. G2/M phases of the cell cycle to arrest tumor growth. (author)

  19. Mapping quantitative trait loci for T lymphocyte subpopulations in peripheral blood in swine

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    Wang Zhi-Peng

    2011-09-01

    Full Text Available Abstract Background Increased disease resistance through improved general immune capacity would be beneficial for the welfare and productivity of farm animals. T lymphocyte subpopulations in peripheral blood play an important role in immune capacity and disease resistance in animals. However, very little research to date has focused on quantitative trait loci (QTL for T lymphocyte subpopulations in peripheral blood in swine. Results In the study, experimental animals consist of 446 piglets from three different breed populations. To identify QTL for T lymphocyte subpopulations in peripheral blood in swine, the proportions of CD4+, CD8+, CD4+CD8+, CD4+CD8-, CD4-CD8+, and CD4-CD8- T cells and the ratio of CD4+:CD8+ T cells were measured for all individuals before and after challenge with modified live CSF (classical swine fever vaccine. Based on the combined data of individuals from three breed populations, genome-wide scanning of QTL for these traits was performed based on a variance component model, and the genome wide significance level for declaring QTL was determined via permutation tests as well as FDR (false discovery rate correction. A total of 27 QTL (two for CD4+CD8+, one for CD4+CD8-, three for CD4-CD8+, two for CD4-CD8-, nine for CD4+, two for CD8+, and eight for CD4+:CD8+ ratio were identified with significance level of FDR FDR FDR Conclusions Within these QTL regions, a number of known genes having potential relationships with the studied traits may serve as candidate genes for these traits. Our findings herein are helpful for identification of the causal genes underlying these immune-related trait and selection for immune capacity of individuals in swine breeding in the future.

  20. Identification of CD3+ T lymphocytes in the green turtle Chelonia mydas

    Science.gov (United States)

    Munoz, F.A.; Estrada-Parra, S.; Romero-Rojas, A.; Work, T.M.; Gonzalez-Ballesteros, E.; Estrada-Garcia, I.

    2009-01-01

    To understand the role of the immune system with respect to disease in reptiles, there is the need to develop tools to assess the host's immune response. An important tool is the development of molecular markers to identify immune cells, and these are limited for reptiles. We developed a technique for the cryopreservation of peripheral blood mononuclear cells and showed that a commercially available anti-CD3 epsilon chain antibody detects a subpopulation of CD3 positive peripheral blood lymphocytes in the marine turtle Chelonia mydas. In the thymus and in skin inoculated with phytohemagglutinin, the same antibody showed the classical staining pattern observed in mammals and birds. For Western blot, the anti-CD3 antibodies identified a 17.6 kDa band in membrane proteins of peripheral blood mononuclear cell compatible in weight to previously described CD3 molecules. This is the first demostration of CD3+ cells in reptiles using specific antibodies. ?? 2009 Elsevier B.V.