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Блокировка Deoxytidine Kinase в активированных лимфоцитах, разрушающих диоксицитидин трифосфатных пулов и кинетических циклов Alters Classicle Kinetics to Yield Memer Disease в Model Multical Sclersis Model.

Автореактивные, аберрантно активированные лимфоциты, которые нацелены на антигены миелина в центральной нервной системе (КНС), являются основными движущими силами аутоиммунного заболевания, множественного склероза (МС). Расширяющиеся клетки, включая активированные лимфоциты, требуют деоксирибонуклеосайд трифосматы (dNTPs) для воспроизведения ДНК. dNTP могут быть синтезированы по новообразующему пути из прекурсоров, таких, как глюкоза и аминокислоты, или по пути спасения деоксирибонуклеосайда от внеклеточных дексирибонуклеозидов. Deoxytidine cinase (dCK) — энзим, ограничивающий скорость на пути

Совпадение в аннотации оригинала
Autoreactive, aberrantly activated lymphocytes that target myelin antigens in the central nervous system (CNS) are primary drivers of the au … st that dCK activity is required to supply needed dNTPs and to enable rapid cell division following lymphocyte activation against autoantigens in EAE mouse models.

Oxidized low-density lipoproteins induce tissue factor expression in T-lymphocytes via activation of lectin-like oxidized low-density lipoprotein receptor-1.

AIMS: T-lymphocytes plays an important role in the pathophysiology of acute coronary syndromes. T-cell activation in vitro by pro-inflammatory cytokines may lead to functional tissue factor (TF) expression, indicating a possible contribution of immunity to thrombosis. Oxidized low-density lipoproteins (oxLDLs) are found abundantly in atherosclerotic plaques. We aimed at evaluating the effects of oxLDLs on TF expression in T cells and the role of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). METHODS AND RESULTS: CD3+ cells were isolated from healthy volunteers. Gene, pro

Comprehensive Analysis of the Activation and Proliferation Kinetics and Effector Functions of Human Lymphocytes, and Antigen Presentation Capacity of Antigen-Presenting Cells in Xenogeneic Graft-Versus-Host Disease.

Xenogeneic graft-versus-host disease (GVHD) models in highly immunodeficient mice are currently being used worldwide to investigate human immune responses against foreign antigens in vivo. However, the individual roles of CD4+ and CD8+ T cells, and donor/host hematopoietic and nonhematopoietic antigen-presenting cells (APCs) in the induction and development of GVHD have not been fully investigated. In the present study, we comprehensively investigated the immune responses of human T cells and the antigen presentation capacity of donor/host hematopoietic and nonhematopoietic APCs in xenogeneic

CD47 agonist peptides induce programmed cell death in refractory chronic lymphocytic leukemia B cells via PLCγ1 activation: evidence from mice and humans.

BACKGROUND: Chronic lymphocytic leukemia (CLL), the most common adulthood leukemia, is characterized by the accumulation of abnormal CD5+ B lymphocytes, which results in a progressive failure of the immune system. Despite intense research efforts, drug resistance remains a major cause of treatment failure in CLL, particularly in patients with dysfunctional TP53. The objective of our work was to identify potential approaches that might overcome CLL drug refractoriness by examining the pro-apoptotic potential of targeting the cell surface receptor CD47 with serum-stable agonist peptides. METHOD

Bidirectional coupling between ryanodine receptors and Ca2+ release-activated Ca2+ (CRAC) channel machinery sustains store-operated Ca2+ entry in human T lymphocytes.

The expression and functional significance of ryanodine receptors (RyR) were investigated in resting and activated primary human T cells. RyR1, RyR2, and RyR3 transcripts were detected in human T cells. RyR1/2 transcript levels increased, whereas those of RyR3 decreased after T cell activation. RyR1/2 protein immunoreactivity was detected in activated but not in resting T cells. The RyR agonist caffeine evoked Ca(2+) release from the intracellular store in activated T cells but not in resting T cells, indicating that RyR are functionally up-regulated in activated T cells compared with resting

Two cases of chronic active Epstein-Barr virus infection in which EBV-specific cytotoxic T lymphocyte was induced after allogeneic bone marrow transplantation.

CAEBV is a high mortality and morbidity disease with life-threatening complications. Nevertheless, the treatment regimens for CAEBV have not yet been established. Although some reports have described CAEBV therapy involving treatments such as antiviral drugs, immunomodulatory agents, and immunochemotherapy, none of these treatments have been demonstrated to be effective. The only treatment reported to be effective is allogeneic SCT. However, the complications of SCT are severe, so treatment results have been poor. Recently, immunotherapy has been devised, but this is still in the developmental

Antitumor activity in melanoma and anti-self responses in a phase I trial with the anti-cytotoxic T lymphocyte-associated antigen 4 monoclonal antibody CP-675,206.

PURPOSE: Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) blockade with CP-675,206, a fully human anti-CTLA4 monoclonal antibody, may break peripheral immunologic tolerance leading to effective immune responses to cancer in humans. A phase I trial was conducted to test the safety of CP-675,206. PATIENTS AND METHODS: Thirty-nine patients with solid malignancies (melanoma, n = 34; renal cell, n = 4; colon, n = 1) received an intravenous (IV) infusion of CP-675,206 at seven dose levels. The primary objective was to determine the maximum-tolerated dose and the recommended phase II dose. RESUL

Total lymphocyte count, hemoglobin, and delayed-type hypersensitivity as predictors of death and AIDS illness in HIV-1-infected women receiving highly active antiretroviral therapy.

BACKGROUND: Total lymphocyte count (TLC) and hemoglobin level have been suggested as useful and inexpensive parameters to indicate need for HAART in settings in which CD4 cell counts are unavailable. If delayed-type hypersensitivity (DTH) response predicts clinical response in persons using highly active antiretroviral therapy (HAART), it may also prove useful in resource-poor settings. OBJECTIVE: To examine whether TLC, hemoglobin, and DTH response observed prior to initiation of HAART predict post-HAART clinical response. DESIGN: Prospective cohort study. PARTICIPANTS: 873 women in the Wo

Tonsillar B cells do not express PSGL-1, but a significant fraction displays the cutaneous lymphocyte antigen and exhibits effective E- and P-selectin ligand activity.

Skin-homing T cells are defined by the expression of the cutaneous lymphocyte-associated antigen (CLA) which enables the cells to selectively bind to vascular endothelial E-selectin close to sites of cutaneous inflammation, an initial step in the effective extravasation from blood into the inflamed tissue. Essentially all CLA on T cells decorates the backbone of the P-selectin glycoprotein ligand-1 (PSGL-1). In this study we show that human peripheral blood B cells (PBBC) and tonsillar B cells (TBC) do not display PSGL-1 in fluorescence-activated cell sorter analysis using different murine mon

Use of a high-affinity peptide that aborts MHC-restricted cytotoxic T lymphocyte activity against multiple viruses in vitro and virus-induced immunopathologic disease in vivo.

Binding of a specific peptide(s) from a viral protein to major histocompatibility complex (MHC) class I molecules is a critical step in the activation of CD8(+) cytotoxic T lymphocytes (CTLs). Once activated, CTLs can cause lethal disease in an infected host, for example, by killing virus-containing ependymal and ventricular cells in the central nervous system or viral protein-expressing beta cells in the pancreatic islets of Langerhans. Here we describe the usage of a designed (not natural) high-affinity peptide to compete with viral peptide(s)-MHC binding. This peptide blocks virus-induced C

Elevated serum levels of interleukin-4 and interleukin-6 in patients with common variable immunodeficiency (CVI) are associated with chronic immune activation and low numbers of CD4+ lymphocytes.

Serum immunoreactive interleukin (IL-)1 alpha, IL-4, IL-6 and tumor necrosis factor (TNF) alpha were measured in 42 patients with primary hypogammaglobulinemia (25 common variable immunodeficiency (CVI), 10 congenital hypogammaglobulinemia (CH), 7 X-linked agammaglobulinemia (XLA), and in 21 healthy controls. The cytokine levels were correlated to other immunological parameters including serum levels of neopterin and soluble CD8 (sCD8) antigen. IL-6 was detectable in 48% and IL-4 in 36% of the CVI patients, but in none of the controls. Seventy-five percent of the CVI patients with elevated IL-

Resistance in murine schistosomiasis is contingent on activated IL-2 receptor-bearing L3T4+ lymphocytes, negatively regulated by Lyt-2+ cells, and uninfluenced by the presence of IL-4.

These studies assess the roles of subpopulations of T lymphocytes in inducing and modulating resistance to Schistosoma mansoni. C57BL/6 mice were depleted in vivo of L3T4+, Lyt-1+, Lyt-2+, IL-2R+ cells, or IL-4 by administration of appropriate mAb. Resistance and various correlative parameters of the immune response were studied in normal, depleted, and congenitally athymic mice. Depletion of T lymphocytes by anti-L3T4 or anti-IL-2R mAb reduced the development and expression of resistance, IgG2a and IgE antibody formation, and delayed type hypersensitivity reactivity against schistosome Ag. De

Variants of a human monocytic leukemia cell line (THP-1): induction of differentiation by retinoic acid, interferon-gamma, and T-lymphocyte-derived differentiation-inducing activity.

Induction of terminal differentiation of two variant sublines derived from the human monocytic leukemia cell line THP-1 by all-trans-beta-retinoic acid (RA) was studied. One of the variants was approximately 10 times more resistant to RA and the other, approximately 10 times more sensitive than the parent THP-1. Differentiation of the RA-resistant variant could be induced by immune interferon (IFN-gamma) and a T-lymphocyte-derived lymphokine of a differentiation-inducing activity (DIA), alone or in combination with 10 nM RA. These induced cells showed many of functional monocyte and/or macroph

INF-γ/TGF-β1-primed umbilical cord mesenchymal stem cells boost the T-lymphocytes activity: Modulation of CD25 expression and IL-6 secretion.

BACKGROUND: Mesenchymal stromal/stem cells (MSCs) have potent immunomodulatory abilities, particularly in a milieu of hyperactive immune system, through secreting a number of cytokines, growth factors, bioactive compounds and peptides, and by cell-cell contact. During viral infection, failure of immuno-neutralization of the viral particles, recruits T-lymphocytes (T-cells) that clear the virally-infected cells. MSCs greatly potentiate T-cells anti-viral activity. OBJECTIVE: The objective of this study is to assess the ability of the cytokine-primed MSCs to activated T-cells, towards an antivi

The utility of neutrophil-to-lymphocyte ratio determined at initial diagnosis in predicting disease stage and discriminating between active and stable disease in patients with sarcoidosis: a cross-sectional study.

OBJECTIVE: To evaluate the utility of neutrophil-lymphocyte ratio (NLR) determined at initial diagnosis in predicting advanced disease stage and discriminating between active and stable disease in sarcoidosis. METHODS: A total of 465 patients with biopsy-proven sarcoidosis (age: 47 years, 70.5% females) were included in this retrospective cross-sectional study. Data on patient demographics, sarcoidosis stage, clinical status (stable and active), anti-inflammatory treatments, complete blood count, and inflammatory markers including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)

Computational Analysis Reveals a Critical Point Mutation in the N-Terminal Region of the Signaling Lymphocytic Activation Molecule Responsible for the Cross-Species Infection with Canine Distemper Virus.

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the n-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown, partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed th

After Experimental Trypanosoma cruzi Infection, Dying Hepatic CD3+TCRαβ+B220+ T Lymphocytes Are Rescued from Death by Peripheral T Cells and Become Activated.

The unusual phenotype of CD3+ T lymphocyte expressing B220, a marker originally attributed to B lymphocytes, was first observed in the liver of Fas/Fas-L-deficient mice as a marker of apoptotic T lymphocytes. However, other CD3+B220+ T lymphocyte populations were later described in the periphery as functional cytotoxic or regulatory cells, for example. Then, in this work, we studied whether hepatic CD3+B220+ T lymphocytes could play a role in experimental Trypanosoma cruzi infection. In control and infected mice, we observed two subpopulations that could be discerned based on CD117 expression,

HMGB1 released from intestinal epithelia damaged by cholera toxin adjuvant contributes to activation of mucosal dendritic cells and induction of intestinal cytotoxic T lymphocytes and IgA.

Cholera toxin (CT) is a potent mucosal adjuvant and oral administration of ovalbumin (OVA) antigens plus CT induces OVA-specific CD8+ cytotoxic T lymphocytes (CTLs) and IgA production in intestinal mucosa. However, the mechanisms of induction of these immune responses remain unknown. Intestinal OVA-specific CD8+ CTLs were not induced by oral administration of the CT active (CTA) or CT binding (CTB) subunit as an adjuvant and CD11c+ DCs were involved in cross-priming of intestinal CTLs. CD8+CD103+CD11c+CD11b-DCs and DCIR2+CD103+CD11c+CD11b+ DCs were distributed in the intestinal lamina propria

OSU-DY7, a novel D-tyrosinol derivative, mediates cytotoxicity in chronic lymphocytic leukaemia and Burkitt lymphoma through p38 mitogen-activated protein kinase pathway.

Drug resistance and associated immune deregulation limit use of current therapies in chronic lymphocytic leukaemia (CLL), thus warranting alternative therapy development. Herein we demonstrate that OSU-DY7, a novel D-tyrosinol derivative targeting p38 mitogen-activated protein kinase (MAPK), mediates cytotoxicity in lymphocytic cell lines representing CLL (MEC-1), acute lymphoblastic leukaemia (697 cells), Burkitt lymphoma (Raji and Ramos) and primary B cells from CLL patients in a dose- and time-dependent manner. The OSU-DY7-induced cytotoxicity is dependent on caspase activation, as evidence