661 results
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202. Forthcoming papers.
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IMMUNOLOGY , *BIBLIOGRAPHY , *DENDRITIC cells , *DEOXYRIBONUCLEOTIDES , *NUCLEOTIDES , *T cells , *LYMPHOCYTES - Abstract
The article presents a list of articles related to immunology. The articles include "Monocyte-Derived Dendritic Cells From Horses Differ From DC of Humans and Mice," by Susanne Mauel, Falko Steinbach and Hanns Ludwig, "Extended Sequence Preferences for Oligodeoxyribonucleotide Activity," by Peter Lenert, Adam Goeken and Robert Ashman, "On the Logic of Positive Selection," by Melvin Cohn, "CTLA-4 Interacts With Stat5 and Inhibits Stat5-Mediated Transcription," by M. Srahna, L. Van Grunsven, J. Remacle and Peter Vandenberghe, and "Peritoneal Macrophages Supress T Cell Activation by Amino Acid Catabolism," by R. Matlack, K. Yeh, L. Rosini, D. Gonzalez, J. Taylor, D. Silberman, A. Pennello and James Riggs.
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- 2006
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203. Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cells.
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Withoff, S, Bijman, M N A, Stel, A J, Delahaye, L, Calogero, A, Jonge, M W A de, Kroesen, B J, and Leij, L de
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HYBRIDOMAS , *T cells - Abstract
This paper describes a bi-specific antibody, which was called BIS20×3. It retargets CD3ε-positive cells (T-cells) to CD20-positive cells and was obtained by hybrid-hybridoma fusion. BIS20×3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics associated with both of its chains. Cross-linking of BIS20×3 on Ramos cells leads to DNA fragmentation percentages similar to those obtained after Rituximab-cross-linking. Cross-linking of BIS20×3 on T-cells using cross-linking F(ab′)2-fragments induced T-cell activation. Indirect cross-linking of T-cell-bound BIS20×3 via Ramos cells hyper-activated the T-cells. Furthermore, it was demonstrated that BIS20×3 effectively re-targets T-cells to B-cells, leading to high B-cell cytotoxicity. The results presented in this paper show that BIS20×3 is fully functional in retargeting T-cells to B-cells and suggest that B-cell lymphomas may represent ideal targets for T-cell retargeting bi-specific antibodies, because the retargeted T-cell is maximally stimulated in the presence of B-cells. Additionally, since B-cells may up-regulate CD95/Fas expression upon binding of CD20-directed antibodies, B-cells will become even more sensitive for T-cell mediated killing via CD95L/FasL, and therefore supports the intention to use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell malignancies as a treatment modality for these diseases. [ABSTRACT FROM AUTHOR]
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- 2001
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204. Forthcoming papers.
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IMMUNOLOGY , *CYCLIC adenylic acid , *T cells , *LYMPHOID tissue - Abstract
Reveals topics in the forthcoming issues of the journal "Immunology". Impact of cyclic adenylic acid on T cell response; Architecture of secondary lymphoid tissue in sheep; Calcium influx shutdown during neutrophil apoptosis.
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- 2003
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205. CD38: An important regulator of T cell function.
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Li, Wentao, Liang, Lin, Liao, Qianjin, Li, Yanling, and Zhou, Yanhong
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T cells , *CELL physiology , *CD38 antigen , *EXTRACELLULAR enzymes , *CHIMERIC antigen receptors - Abstract
Cluster of differentiation 38 (CD38) is a multifunctional extracellular enzyme on the cell surface with NADase and cyclase activities. CD38 is not only expressed in human immune cells, such as lymphocytes and plasma cells, but also is abnormally expressed in a variety of tumor cells, which is closely related to the occurrence and development of tumors. T cells are one of the important immune cells in the body. As NAD consuming enzymes, CD38, ART2, SIRT1 and PARP1 are closely related to the number and function of T cells. CD38 may also influence the activity of ART2, SIRT1 and PARP1 through the CD38-NAD+ axis to indirectly affect the number and function of T cells. Thus, CD38-NAD+ axis has a profound effect on T cell activity. In this paper, we reviewed the role and mechanism of CD38+ CD4+ T cells / CD38+ CD8+ T cells in cellular immunity and the effects of the CD38-NAD+ axis on T cell activity. We also summarized the relationship between the CD38 expression level on T cell surface and disease prediction and prognosis, the effects of anti-CD38 monoclonal antibodies on T cell activity and function, and the role of anti-CD38 chimeric antigen receptor (CAR) T cell therapy in tumor immunity. This will provide an important theoretical basis for a comprehensive understanding of the relationship between CD38 and T cells. [Display omitted] • As a NAD consuming enzyme, CD38 is closely related to the number and function of T cells. • The expression of CD38 in CD4+ T cells and CD8+ T cell affects the function of CD4+T cell. • The expression level of CD38 on T cell surface is associated with disease prediction and prognosis. [ABSTRACT FROM AUTHOR]
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- 2022
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206. Characterisation of CD4 T cells in healthy and diseased koalas (Phascolarctos cinereus) using cell-type-specific monoclonal antibodies.
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Mangar, Chandan, Armitage, Charles W., Timms, Peter, Corcoran, Lynn M., and Beagley, Kenneth W.
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CD4 antigen , *T cells , *KOALA , *MONOCLONAL antibodies , *HABITATS , *LYMPHOCYTES , *PHYSIOLOGY - Abstract
The koala ( Phascolarctos cinereus ) is an arboreal herbivorous marsupial that is an Australian icon. Koalas in many parts of Australia are under multiple threats including habitat destruction, dog attacks, vehicular accidents, and infectious diseases such as Chlamydia spp. and the koala retrovirus (KoRV), which may contribute to the incidence of lymphoma and leukaemia in this species. Due to a lack of koala-specific immune reagents and assays there is currently no way to adequately analyse the immune response in healthy, diseased or vaccinated animals. This paper reports the production and characterisation of the first anti-koala CD4 monoclonal antibody (mAb). The koala CD4 gene was identified and used to develop recombinant proteins for mAb production. Fluorochrome-conjugated anti-CD4 mAb was used to measure the levels of CD4 + lymphocytes collected from koala spleens (41.1%, range 20–45.1%) lymph nodes (36.3%, range 19–55.9%) and peripheral blood (23.8%, range 17.3–35%) by flow cytometry. Biotin-conjugated anti-CD4 mAb was used for western blot to determine an approximate size of 52 kDa for the koala CD4 molecule and used in immunohistochemistry to identify CD4 + cells in the paracortical region and germinal centres of spleen and lymph nodes. Using the anti-CD4 mab we showed that CD4 cells from vaccinated, but not control, koalas proliferated following in vitro stimulation with UV-inactivated Chlamydia pecorum and recombinant chlamydial antigens. Since CD4 + T cells have been shown to play a pivotal role in clearing chlamydial infection in both human and mouse infections, using this novel antibody will help determine the role CD4 + T cells play in protection against chlamydial infection in koalas and also enhance our knowledge of how KoRV affects the koala immune system. [ABSTRACT FROM AUTHOR]
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- 2016
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207. An SEU-Resilient SRAM Bitcell in 65-nm CMOS Technology.
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Chen, Qingyu, Wang, Haibin, Chen, Li, Li, Lixiang, Zhao, Xing, Liu, Rui, Chen, Mo, and Li, Xuantian
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COMPLEMENTARY metal oxide semiconductors , *PROTONS , *ELECTRIC potential , *ERROR rates , *T cells - Abstract
This paper presents an SEU-resilient 12 T SRAM bitcell. Simulation results demonstrate that it has higher critical charge than the traditional 6 T cell. Alpha and proton testing results validate that it has a lower soft error rate compared to the reference designs for all data patterns and supply voltage levels. The improvement in SEU tolerance is achieved at the expense of 2X area penalty. [ABSTRACT FROM AUTHOR]
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- 2016
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208. The use and abuse of immune indices in nutritional immunology studies.
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Selvaraj, Ramesh K., Shanmugasundaram, Revathi, and Rengasamy, Ravikumar
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IMMUNE system , *NUTRITIONAL immunology , *POULTRY feeding , *PHOSPHORYLATION , *CYTOKINES , *T cells - Abstract
The immune system is complex, with redundant and overlapping functions. Identifying the correct immune parameters to study the immune status of an animal is challenging. Nutritional immunologists often measure different isotypes of antibodies, hematological parameters, parasite loads, functional assays of macrophages and T cells, pro- and anti-inflammatory cytokines, phosphorylation status of proteins involved in signaling pathways, and several other parameters to identify the immune status of birds. Papers in which authors misinterpret immune parameters are common. This article discusses the drawbacks of some of the common interpretations of several immunological assays available for nutritional immunologists. [ABSTRACT FROM AUTHOR]
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- 2016
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209. A Novel Peptide Binding Prediction Approach for HLA-DR Molecule Based on Sequence and Structural Information.
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Li, Zhao, Zhao, Yilei, Pan, Gaofeng, Tang, Jijun, and Guo, Fei
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PEPTIDE analysis , *ALLELES , *ANTIGENS , *BINDING sites , *CELL receptors , *HISTOCOMPATIBILITY , *IMMUNITY , *RESEARCH funding , *T cells , *HLA-B27 antigen , *DATA analysis software , *DESCRIPTIVE statistics , *SEQUENCE analysis - Abstract
MHC molecule plays a key role in immunology, and the molecule binding reaction with peptide is an important prerequisite for T cell immunity induced. MHC II molecules do not have conserved residues, so they appear as open grooves. As a consequence, this will increase the difficulty in predicting MHC II molecules binding peptides. In this paper, we aim to propose a novel prediction method for MHC II molecules binding peptides. First, we calculate sequence similarity and structural similarity between different MHC II molecules. Then, we reorder pseudosequences according to descending similarity values and use a weight calculation formula to calculate new pocket profiles. Finally, we use three scoring functions to predict binding cores and evaluate the accuracy of prediction to judge performance of each scoring function. In the experiment, we set a parameter α in the weight formula. By changing α value, we can observe different performances of each scoring function. We compare our method with the best function to some popular prediction methods and ultimately find that our method outperforms them in identifying binding cores of HLA-DR molecules. [ABSTRACT FROM AUTHOR]
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- 2016
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210. Quantitative Contribution of IL2Rγ to the Dynamic Formation of IL2-IL2R Complexes.
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Ponce, Luis F., García-Martínez, Karina, and León, Kalet
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INTERLEUKIN-2 receptors , *GROWTH factors , *CELL membranes , *LIGAND binding (Biochemistry) , *CELLULAR signal transduction - Abstract
Interleukin-2 (IL2) is a growth factor for several immune cells and its function depends on its binding to IL2Rs in the cell membrane. The most accepted model for the assembling of IL2-IL2R complexes in the cell membrane is the Affinity Conversion Model (ACM). This model postulates that IL2R receptor association is sequential and dependent on ligand binding. Most likely free IL2 binds first to IL2Rα, and then this complex binds to IL2Rβ, and finally to IL2Rγ (γc). However, in previous mathematical models representing this process, the binding of γc has not been taken into account. In this work, the quantitative contribution of the number of IL2Rγ chain to the IL2-IL2R apparent binding affinity and signaling is studied. A mathematical model of the affinity conversion process including the γ chain in the dynamic, has been formulated. The model was calibrated by fitting it to experimental data, specifically, Scatchard plots obtained using human cell lines. This paper demonstrates how the model correctly explains available experimental observations. It was estimated, for the first time, the value of the kinetic coefficients of IL2-IL2R complexes interaction in the cell membrane. Moreover, the number of IL2R components in different cell lines was also estimated. It was obtained a variable distribution in the number of IL2R components depending on the cell type and the activation state. Of most significance, the study predicts that not only the number of IL2Rα and IL2Rβ, but also the number of γc determine the capacity of the cell to capture and retain IL2 in signalling complexes. Moreover, it is also showed that different cells might use different pathways to bind IL2 as consequence of its IL2R components distribution in the membrane. [ABSTRACT FROM AUTHOR]
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- 2016
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211. Panoptic clinical review of the current and future treatment of relapsed/refractory T-cell lymphomas: Cutaneous T-cell lymphomas.
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Zinzani, Pier Luigi, Bonthapally, Vijayveer, Huebner, Dirk, Lutes, Richard, Chi, Andy, and Pileri, Stefano
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LYMPHOMAS , *T cells , *CANCER relapse , *CANCER chemotherapy , *INTERFERONS , *MYCOSIS fungoides - Abstract
Primary cutaneous T-cell lymphomas (CTCLs), such as mycosis fungoides and Sézary syndrome, are a rare group of non-Hodgkin lymphomas, usually treated using a multimodal approach. Unfortunately, many patients go on to develop relapsed/refractory disease. Systemic treatment for relapsed/refractory CTCL has historically relied on chemotherapies and interferons, and while active, responses are often short-lived. Three drugs are now approved in the US to treat relapsed/refractory CTCL including the oral retinoid, bexarotene, and histone deacetylase inhibitors, romidepsin and vorinostat. Although response rates are typically <35%, romidepsin and vorinostat can induce some durable responses in heavily pretreated patients and alleviate bothersome symptoms, such as pruritus. New studies indicate that the anti-CD30 antibody-drug conjugate brentuximab vedotin, anti-CCR4 antibody mogamulizumab, and fusion protein immunotoxin A-dmDT390-bisFv(UCHT1) may be particularly active in this setting. In this paper, we present an exhaustive review of the clinical data on current and possible future drug treatment options for relapsed/refractory CTCL. [ABSTRACT FROM AUTHOR]
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- 2016
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212. A Generic Mechanism for Enhanced Cytokine Signaling via Cytokine-Neutralizing Antibodies.
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Shulgin, Boris, Helmlinger, Gabriel, and Kosinsky, Yuri
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CYTOKINES , *CELLULAR signal transduction , *IMMUNOGLOBULINS , *IMMUNE response , *DRUG efficacy - Abstract
Enhancement or inhibition of cytokine signaling and corresponding immune cells responses are critical factors in various disease treatments. Cytokine signaling may be inhibited by cytokine-neutralizing antibodies (CNAs), which prevents further activation of cytokine receptors. However, CNAs may result in enhanced—instead of inhibitory—cytokine signaling (an “agonistic effect”) in various in vitro and in vivo experiments. This may lead to lack of efficacy or adverse events for cytokine-inhibiting based medicines. Alternatively, cytokine-antibody complexes may produce stronger signaling vs. cytokine alone, thereby increasing the efficacy of stimulating cytokine-based drugs, at equal or lower cytokine doses. In this paper, the effect of cytokine signaling enhancement by a CNA was studied in a generic mathematical model of interleukin-4 (IL-4) driven T-cell proliferation. The occurrence of the agonistic effect depends upon the antibody-to-cytokine binding affinity and initial concentrations of antibody and cytokine. Model predictions were in agreement with experimental studies. When the cytokine receptor consists of multiple subunits with substantially differing affinities (e.g., IL-4 case), the choice of the receptor chain to be blocked by the antibody is critical, for the agonistic effect to appear. We propose a generic mechanism for the effect: initially, binding of the CNA to the cytokine reduces free cytokine concentration; yet, cytokine molecules bound within the cytokine-CNA complex—and released later and over time—are “rescued” from earlier clearance via cellular internalization. Hence, although free cytokine-dependent signalling may be less potent initially, it will also be more sustained over time; and given non-linear dynamics, it will lead ultimately to larger cellular effector responses, vs. the same amount of free cytokine in the absence of CNA. We suggest that the proposed mechanism is a generic property of {cytokine, CNA, receptor} triads, both in vitro and in vivo, and can occur in a predictable fashion for a variety of cytokines of the immune system. [ABSTRACT FROM AUTHOR]
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- 2016
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213. Investigating the Consequences of Interference between Multiple CD8+ T Cell Escape Mutations in Early HIV Infection.
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Garcia, Victor, Feldman, Marcus W., and Regoes, Roland R.
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HIV infections , *CD8 antigen , *T cells , *GENETIC mutation , *COMPUTATIONAL biology - Abstract
During early human immunodeficiency virus (HIV) infection multiple CD8+ T cell responses are elicited almost simultaneously. These responses exert strong selective pressures on different parts of HIV’s genome, and select for mutations that escape recognition and are thus beneficial to the virus. Some studies reveal that the later these escape mutations emerge, the more slowly they go to fixation. This pattern of escape rate decrease(ERD) can arise by distinct mechanisms. In particular, in large populations with high beneficial mutation rates interference among different escape strains –an effect that can emerge in evolution with asexual reproduction and results in delayed fixation times of beneficial mutations compared to sexual reproduction– could significantly impact the escape rates of mutations. In this paper, we investigated how interference between these concurrent escape mutations affects their escape rates in systems with multiple epitopes, and whether it could be a source of the ERD pattern. To address these issues, we developed a multilocus Wright-Fisher model of HIV dynamics with selection, mutation and recombination, serving as a null-model for interference. We also derived an interference-free null model assuming initial neutral evolution before immune response elicitation. We found that interference between several equally selectively advantageous mutations can generate the observed ERD pattern. We also found that the number of loci, as well as recombination rates substantially affect ERD. These effects can be explained by the underexponential decline of escape rates over time. Lastly, we found that the observed ERD pattern in HIV infected individuals is consistent with both independent, interference-free mutations as well as interference effects. Our results confirm that interference effects should be considered when analyzing HIV escape mutations. The challenge in estimating escape rates and mutation-associated selective coefficients posed by interference effects cannot simply be overcome by improved sampling frequencies or sizes. This problem is a consequence of the fundamental shortcomings of current estimation techniques under interference regimes. Hence, accounting for the stochastic nature of competition between mutations demands novel estimation methodologies based on the analysis of HIV strains, rather than mutation frequencies. [ABSTRACT FROM AUTHOR]
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- 2016
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214. The case for an autoimmune aetiology of type 1 diabetes.
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Mannering, S. I., Pathiraja, V., and Kay, T. W. H.
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ETIOLOGY of diseases , *TYPE 1 diabetes , *PANCREATIC beta cells , *HOMEOSTASIS , *AUTOIMMUNE diseases - Abstract
Type 1 diabetes (T1D) develops when there are insufficient insulinproducing beta cells to maintain glucose homeostasis. The prevailing view has been that T1D is caused by immune-mediated destruction of the pancreatic beta cells. However, several recent papers have challenged the long-standing paradigm describing T1D as a tissue-specific autoimmune disease. These authors have highlighted the gaps in our knowledge and understanding of the aetiology of T1D in humans. Here we review the evidence and argue the case for the autoimmune basis of human T1D. In particular, recent analysis of human islet-infiltrating T cells brings important new evidence to this question. Further data in support of the autoimmune basis of T1D from many fields, including genetics, experimental therapies and immunology, is discussed. Finally, we highlight some of the persistent questions relating to the pathogenesis of human type 1 diabetes that remain to be answered. [ABSTRACT FROM AUTHOR]
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- 2016
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215. Modeling the Slow CD4+ T Cell Decline in HIV-Infected Individuals.
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Wang, Sunpeng, Hottz, Patricia, Schechter, Mauro, and Rong, Libin
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CD4 antigen , *HIV-positive persons , *T cells , *APOPTOSIS , *CYTOKINES - Abstract
The progressive loss of CD4+ T cell population is the hallmark of HIV-1 infection but the mechanism underlying the slow T cell decline remains unclear. Some recent studies suggested that pyroptosis, a form of programmed cell death triggered during abortive HIV infection, is associated with the release of inflammatory cytokines, which can attract more CD4+ T cells to be infected. In this paper, we developed mathematical models to study whether this mechanism can explain the time scale of CD4+ T cell decline during HIV infection. Simulations of the models showed that cytokine induced T cell movement can explain the very slow decline of CD4+ T cells within untreated patients. The long-term CD4+ T cell dynamics predicted by the models were shown to be consistent with available data from patients in Rio de Janeiro, Brazil. Highly active antiretroviral therapy has the potential to restore the CD4+ T cell population but CD4+ response depends on the effectiveness of the therapy, when the therapy is initiated, and whether there are drug sanctuary sites. The model also showed that chronic inflammation induced by pyroptosis may facilitate persistence of the HIV latent reservoir by promoting homeostatic proliferation of memory CD4+ cells. These results improve our understanding of the long-term T cell dynamics in HIV-1 infection, and support that new treatment strategies, such as the use of caspase-1 inhibitors that inhibit pyroptosis, may maintain the CD4+ T cell population and reduce the latent reservoir size. [ABSTRACT FROM AUTHOR]
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- 2015
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216. Mast cells and dendritic cells form synapses that facilitate antigen transfer for T cell activation.
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Carroll-Portillo, Amanda, Cannon, Judy L., Riet, Joost te, Holmes, Anna, Yuko Kawakami, Toshiaki Kawakami, Cambi, Alessandra, and Lidke, Diane S.
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MAST cells , *DENDRITIC cells , *IMMUNE response , *CELL communication , *CYTOKINES , *CELLULAR control mechanisms , *T cells , *BIOLOGICAL crosstalk - Abstract
Mast cells (MCs) produce soluble mediators such as histamine and prostaglandins that are known to influence dendritic cell (DC) function by stimulating maturation and antigen processing. Whether direct cell-cell interactions are important in modulating MC/DC function is unclear . In this paper, we show that direct contact between MCs and DCs occurs and plays an important role in modulating the immune response. Activation of MCs through FceRI cross-linking triggers the formation of stable cell-cell interactions with immature DCs that are reminiscent of the immunological synapse. Direct cellular contact differentially regulates the secreted cytokine profile, indicating that MC modulation of DC populations is influenced by the nature of their interaction. Synapse formation requires integrin engagement and facilitates the transfer of internalized MC-specific antigen from MCs to DCs. The transferred material is ultimately processed and presented by DCs and can activate T cells. The physiological outcomes of the MC-DC synapse suggest a new role for intercellular crosstalk in defining the immune response. [ABSTRACT FROM AUTHOR]
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- 2015
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217. A Stochastic Model for CD4+ T Cell Proliferation and Dissemination Network in Primary Immune Response.
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Boianelli, Alessandro, Pettini, Elena, Prota, Gennaro, Medaglini, Donata, and Vicino, Antonio
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STOCHASTIC models , *CD4 antigen , *T cells , *CELL proliferation , *IMMUNE response , *IMMUNIZATION - Abstract
The study of the initial phase of the adaptive immune response after first antigen encounter provides essential information on the magnitude and quality of the immune response. This phase is characterized by proliferation and dissemination of T cells in the lymphoid organs. Modeling and identifying the key features of this phenomenon may provide a useful tool for the analysis and prediction of the effects of immunization. This knowledge can be effectively exploited in vaccinology, where it is of interest to evaluate and compare the responses to different vaccine formulations. The objective of this paper is to construct a stochastic model based on branching process theory, for the dissemination network of antigen-specific CD4+ T cells. The devised model is validated on in vivo animal experimental data. The model presented has been applied to the vaccine immunization context making references to simple proliferation laws that take into account division, death and quiescence, but it can also be applied to any context where it is of interest to study the dynamic evolution of a population. [ABSTRACT FROM AUTHOR]
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- 2015
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218. Correction to: Transcriptome of CD8+ tumor-infiltrating T cells: a link between diabetes and colorectal cancer.
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Saleh, Reem, Nair, Varun Sasidharan, Murshed, Khaled, Nada, Mohamed Abu, Elkord, Eyad, and Shaheen, Ranad
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COLORECTAL cancer , *T cells , *DIABETES - Abstract
A correction to this paper has been published: https://doi.org/10.1007/s00262-021-02903-w [ABSTRACT FROM AUTHOR]
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- 2021
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219. Publisher Correction: Inhibition of succinate dehydrogenase activity impairs human T cell activation and function.
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Nastasi, Claudia, Willerlev-Olsen, Andreas, Dalhoff, Kristoffer, Ford, Shayne L., Gadsbøll, Anne-Sofie Østergaard, Buus, Terkild Brink, Gluud, Maria, Danielsen, Morten, Litman, Thomas, Bonefeld, Charlotte Mennè, Geisler, Carsten, Ødum, Niels, and Woetmann, Anders
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SUCCINATE dehydrogenase , *T cells - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
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- 2021
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220. Dual-Target CAR-Ts with On- and Off-Tumour Activity May Override Immune Suppression in Solid Cancers: A Mathematical Proof of Concept.
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León-Triana, Odelaisy, Pérez-Martínez, Antonio, Ramírez-Orellana, Manuel, Pérez-García, Víctor M., and Wong, David
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TUMOR treatment , *CELL receptors , *IMMUNE system , *IMMUNOSUPPRESSION , *CELL physiology , *GLIOMAS , *CANCER patients , *TISSUE engineering , *T cells - Abstract
Simple Summary: (CAR)-T cell-based therapies have achieved substantial success against different haematological malignancies. However, results for solid tumours have been limited up to now, in part due to the fact that the immunosuppressive tumour microenvironment inactivates CAR-T cell clones. In this paper we study mathematically the competition of CAR-T and tumour cells, taking into account their immunosuppressive capacity. Using computer simulations, we show that the use of large numbers of CAR-T cells targetting the solid tumour antigens could overcome the immunosuppressive potential of cancer. To achieve such high levels of CAR-T cells we propose, and study in silico, the manufacture and injection of CAR-T cells targetting two antigens: CD19 and a tumour-associated antigen. This strategy lead in our simulations to the expansion of the CAR-T cells injected and the production of a massive army of CAR-T cells targetting the solid tumour, and potentially overcoming its immune suppression capabilities. Thus, our proposed strategy could provide a way to develop successful CAR-T cell therapies against solid tumours. Chimeric antigen receptor (CAR)-T cell-based therapies have achieved substantial success against B-cell malignancies, which has led to a growing scientific and clinical interest in extending their use to solid cancers. However, results for solid tumours have been limited up to now, in part due to the immunosuppressive tumour microenvironment, which is able to inactivate CAR-T cell clones. In this paper we put forward a mathematical model describing the competition of CAR-T and tumour cells, taking into account their immunosuppressive capacity. Using the mathematical model, we show that the use of large numbers of CAR-T cells targetting the solid tumour antigens could overcome the immunosuppressive potential of cancer. To achieve such high levels of CAR-T cells we propose, and study computationally, the manufacture and injection of CAR-T cells targetting two antigens: CD19 and a tumour-associated antigen. We study in silico the resulting dynamics of the disease after the injection of this product and find that the expansion of the CAR-T cell population in the blood and lymphopoietic organs could lead to the massive production of an army of CAR-T cells targetting the solid tumour, and potentially overcoming its immune suppression capabilities. This strategy could benefit from the combination with PD-1 inhibitors and low tumour loads. Our computational results provide theoretical support for the treatment of different types of solid tumours using T cells engineered with combination treatments of dual CARs with on- and off-tumour activity and anti-PD-1 drugs after completion of classical cytoreductive treatments. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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221. Driving Rel-iant Tregs toward an Identity Crisis.
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Li, Amy and Jacks, Tyler
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CELL physiology , *CANCER cell growth , *IMMUNOSUPPRESSION , *TUMOR microenvironment , *T cells - Abstract
Inhibiting Treg cell function in tumors is an attractive strategy to improve anti-cancer immunity. In a pair of papers in Immunity and Cell , Ghosh and colleagues show that the canonical NF-κB subunits p65 and c-Rel have non-redundant, critical roles in promoting Treg cell development and function ( Oh et al., 2017 ). Targeting c-Rel blunts Treg cell immunosuppressive activity in the tumor microenvironment and enhances anti-tumor T cell responses ( Grinberg-Bleyer et al., 2017 ). [ABSTRACT FROM AUTHOR]
- Published
- 2017
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222. Immune responses in newly developed short-lived SAM mice II. SELECTIVELY IMPAIRED T-HELPER CELL ACTIVITY IN <em>IN VITRO</em> ANTIBODY RESPONSE.
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Hosokawa, T., Hosono, M., Hanada, K., Aoike, A., Kawai, K., and Takeda, T.
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T cells , *LEUCOCYTES , *IMMUNOGLOBULINS , *ANTIGENS , *LYMPHOCYTES , *CELL culture - Abstract
New short-lived strains of mice (SAM-P), which have been developed by Takeda et al. (1981), show a defective antibody response to T dependent (TD) antigen in vitro, as demonstrated in the accompanying paper (see page 419). In the present study, we investigated the cellular site of the defect, using a cell culture system. In this paper, it is demonstrated that T-helper (Th) cell activity for the antibody response to TD antigen is impaired, while other cellular immune responses, e.g. mixed leucocyte reaction, cytotoxic T-lymphocyte response, and delayed-type hypersensitivity reaction, are normal. These results suggest that the defect in T-helper subset is limited in helper function for the antibody response, and that the helper function for the cell-mediated immune responses is intact. These two functions of the T-helper subset are apparently regulated in a different manner. The SAM-P strains of mice may thus serve as an appropriate model for studying functional heterogeneity in T-helper/inducer cell subsets. [ABSTRACT FROM AUTHOR]
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- 1987
223. Concanavalin A stimulation of mouse lymphocytes at low concentration II. THE EFFECT OF CONDITIONED MEDIUM FROM PERITONEAL EXUDATE CELLS AND FROM LYMPHOCYTE CULTURES.
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Young, Barbara
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LYMPHOCYTES , *SPLEEN , *EXUDATES & transudates , *CELLS , *CELL culture , *BIOLOGICAL assay , *T cells ,MICE anatomy - Abstract
The first paper in this series reported that it was possible to reconstitute the response of low concentrations of mouse spleen lymphocytes to concanavalin A (Con A) by adding small numbers of peritoneal exudate cells (PEC) to the cultures. In this paper it is shown that the role of the PEC in this system can be partially replaced by conditioned medium (CM) prepared from PEC cultures or completely replaced by CM taken from lymphocytes cultured at optimal concentration. These CM were inactive unless fresh Con A was added to the assay cultures. Activity was present in CM which was incubated with lymphocytes or PEC for the shortest possible time but maximal activity was found after 24 hr of incubation. Activity was also found in CM prepared in the absence of Con A. Only in the case of lymphocytes cultured at optimal concentration for 24 hr was there substantially more activity in the CM thus prepared if Con A was present. PEC preparations depleted of T lymphocytes produced as much activity in CM as the untreated control. CM produced by PEC was less sensitive to heat treatment or to freezing and thawing than that produced by lymphocyte cultures. [ABSTRACT FROM AUTHOR]
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- 1982
224. Abstracts for the ESDR Clinically Oriented Symposium.
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CONFERENCES & conventions , *LYMPHOMAS , *T cells , *IMMUNOGLOBULINS , *B cells , *LYMPHOCYTES - Abstract
This article presents abstracts for various research papers to be presented in the European Society for Dermatological Research's symposium on September 26-28, 1997. These research papers pertain to subjects like the eortic classification for primary cutaneous lymphomas, different prognosis between cutaneous and systemic lymphoproliferative disorders, parapsoriasis and early cutaneous T cell lymphoma, immunoglobulin gene rearrangement of pseudo B-cell lymphomas and prognostic significance of polymerase chain reaction detectable dominant T lymphocyte clones.
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- 1997
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225. Abstracts for the 27th Annual Meeting of the European Society for Dermatological Research.
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MEETINGS , *CYTOKINES , *PROSTAGLANDINS , *DENDRITIC cells , *T cells , *MELANOMA - Abstract
This article presents abstracts for various research papers to be presented in the 27th Annual Meeting of the European Society for Dermatological Research. These research papers pertain to subjects like proinflammatory cytokines and prostaglandins' inducing maturation of potent immunostiumlatory dendritic cells, mediators that mobilize langerhans cells, antigens for the activation of T lymphocytes by skin dendritic cells and vaccination of melanoma patients with peptide-pulsed dendritic cells.
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- 1997
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226. Retraction: "Construction of PD-L1-siRNA and IL-2 DNA loading PEI lipid nanoparticles in activating T cells and treating lung cancer" [AIP Adv. 11(4), 045201 (2021)].
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Gao, Lei, Yu, Shaobin, Lin, Jihong, Chen, Sui, Shen, Zhimin, and Kang, Mingqiang
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T cells , *LUNG cancer , *DNA , *NANOPARTICLES - Abstract
1, PD-L1-SiRNA should be wrapped by PEI-LNP, so PD-L1-SiRNA in the flow chart should be placed in DOPC and other raw materials, and the binding method of PD-L1 antibody and PEI-LNP was incorrectly suggested in the article. The Editor and the Publisher of AIP Advances (ADV) have retracted the referenced paper due to the following data errors and omissions. [Extracted from the article]
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- 2022
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227. Therapeutic Potential of a Combination of Electroacupuncture and Human iPSC-Derived Small Extracellular Vesicles for Ischemic Stroke.
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Deng, Peiying, Wang, Liang, Zhang, Qiongqiong, Chen, Suhui, Zhang, Yamin, Xu, Hong, Chen, Hui, Xu, Yi, He, Wei, Zhang, Jianmin, and Sun, Hua
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EXTRACELLULAR vesicles , *ISCHEMIC stroke , *ELECTROACUPUNCTURE , *PLURIPOTENT stem cells , *REGULATORY T cells , *EXOSOMES , *T cells , *CEREBRAL ischemia - Abstract
This paper aimed to explore the roles of the combination of electroacupuncture (EA) and induced pluripotent stem cell-derived small extracellular vesicles (iPSC-EVs) on mice with ischemic stroke and the underlying mechanisms. A focal cerebral ischemia model was established in C57BL/6 mice through middle cerebral artery occlusion (MCAO). After 3 days, neurological impairment and motor function were examined by performing behavioral tests. The infarct volume and neuronal apoptosis were examined using TTC staining and TUNEL assays. Flow cytometry was performed to assess the proliferation of T lymphocytes. The changes in the interleukin (IL)-33/ST2 axis were evaluated by immunofluorescence and Western blotting. The combination of EA and iPSC-EVs treatment ameliorated neurological impairments and reduced the infarct volume and neuronal apoptosis in MCAO mice. EA plus iPSC-EVs suppressed T helper (Th1) and Th17 responses and promoted the regulatory T cell (Treg) response. In addition, EA plus iPSC-EVs exerted neuroprotective effects by regulating the IL-33/ST2 axis and inhibiting the microglia and astrocyte activation. Taken together, the study shows that EA and iPSC-EVs exerted a synergistic neuroprotective effect in MCAO mice, and this treatment may represent a novel potent therapy for ischemic stroke and damage to other tissues. [ABSTRACT FROM AUTHOR]
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- 2022
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228. Mathematical Modeling and Analysis of Leukemia: Effect of External Engineered T Cells Infusion.
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Agarwal, Manju and Bhadauria, Archana S.
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LEUKEMIA , *T cells , *CANCER cells , *STABILITY theory , *MATHEMATICAL models - Abstract
In this paper, a nonlinear model is proposed and analyzed to study the spread of Leukemia by considering the effect of genetically engineered patients T cells to attack cancer cells. The model is governed by four dependent variables namely; naive or susceptible blood cells, infected or dysfunctional blood cells, cancer cells and immune cells. The model is analyzed by using the stability theory of differential equations and numerical simulation. We have observed that the system is stable in the local and global sense if antigenicity rate or rate of stimulation of immune cells is greater than a threshold value dependent on the density of immune cells. Further, external infusion of T cells (immune cells) reduces the concentration of cancer cells and infected cells in the blood. It is observed that the infected cells decrease with the increase in antigenicity rate or stimulation rate of immune response due to abnormal cancer cells present in the blood. This indicates that immune cells kill cancer cells on being stimulated and as antigenicity rate increases rate of destruction of cancer cells also increase leading to decrease in the concentration of cancer cells in the body. This decrease in cancer cells further causes decrease in the concentration of infected or dysfunctional cells in the body. [ABSTRACT FROM AUTHOR]
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- 2015
229. Atorvastatin Improves Inflammatory Response in Atherosclerosis by Upregulating the Expression of GARP.
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Zhao, Xiaoqi, Liu, Yuzhou, Zhong, Yucheng, Liu, Bo, Yu, Kunwu, Shi, Huairui, Zhu, Ruirui, Meng, Kai, Zhang, Wei, Wu, Bangwei, and Zeng, Qiutang
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ATORVASTATIN , *INFLAMMATION , *ATHEROSCLEROSIS , *GENE expression , *ATHEROSCLEROTIC plaque , *T cells - Abstract
Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-β. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-β in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE−/− mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-β1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells. [ABSTRACT FROM AUTHOR]
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- 2015
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230. T Helper 17/Regulatory T Cell Balance and Experimental Models of Peritoneal Dialysis-Induced Damage.
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Liappas, Georgios, Gónzalez-Mateo, Guadalupe Tirma, Majano, Pedro, Sánchez- Tomero, José Antonio, Ruiz-Ortega, Marta, Rodrigues Díez, Raquel, Martín, Pilar, Sanchez-Díaz, Raquel, Selgas, Rafael, López-Cabrera, Manuel, and Aguilera Peralta, Abelardo
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TREATMENT of chronic kidney failure , *BIOMARKERS , *NONSTEROIDAL anti-inflammatory agents , *PERITONEAL dialysis , *PERITONEUM , *PERITONEUM diseases , *T cells , *CYCLOOXYGENASE 2 , *FIBROSIS , *DISEASE risk factors - Abstract
Fibrosis is a general complication in many diseases. It is the main complication during peritoneal dialysis (PD) treatment, a therapy for renal failure disease. Local inflammation and mesothelial to mesenchymal transition (MMT) are well known key phenomena in peritoneal damage during PD. New data suggest that, in the peritoneal cavity, inflammatory changes may be regulated at least in part by a delicate balance between T helper 17 and regulatory T cells. This paper briefly reviews the implication of the Th17/Treg-axis in fibrotic diseases. Moreover, it compares current evidences described in PD animal experimental models, indicating a loss of Th17/Treg balance (Th17 predominance) leading to peritoneal damage during PD. In addition, considering the new clinical and animal experimental data, new therapeutic strategies to reduce the Th17 response and increase the regulatory T response are proposed. Thus, future goals should be to develop new clinical biomarkers to reverse this immune misbalance and reduce peritoneal fibrosis in PD. [ABSTRACT FROM AUTHOR]
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- 2015
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231. Accurate Prediction of Immunogenic T-Cell Epitopes from Epitope Sequences Using the Genetic Algorithm-Based Ensemble Learning.
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Zhang, Wen, Niu, Yanqing, Zou, Hua, Luo, Longqiang, Liu, Qianchao, and Wu, Weijian
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IMMUNOGENETICS , *T cells , *EPITOPES , *GENETIC algorithms , *IMMUNE response , *STATISTICAL significance - Abstract
Background: T-cell epitopes play the important role in T-cell immune response, and they are critical components in the epitope-based vaccine design. Immunogenicity is the ability to trigger an immune response. The accurate prediction of immunogenic T-cell epitopes is significant for designing useful vaccines and understanding the immune system. Methods: In this paper, we attempt to differentiate immunogenic epitopes from non-immunogenic epitopes based on their primary structures. First of all, we explore a variety of sequence-derived features, and analyze their relationship with epitope immunogenicity. To effectively utilize various features, a genetic algorithm (GA)-based ensemble method is proposed to determine the optimal feature subset and develop the high-accuracy ensemble model. In the GA optimization, a chromosome is to represent a feature subset in the search space. For each feature subset, the selected features are utilized to construct the base predictors, and an ensemble model is developed by taking the average of outputs from base predictors. The objective of GA is to search for the optimal feature subset, which leads to the ensemble model with the best cross validation AUC (area under ROC curve) on the training set. Results: Two datasets named ‘IMMA2’ and ‘PAAQD’ are adopted as the benchmark datasets. Compared with the state-of-the-art methods POPI, POPISK, PAAQD and our previous method, the GA-based ensemble method produces much better performances, achieving the AUC score of 0.846 on IMMA2 dataset and the AUC score of 0.829 on PAAQD dataset. The statistical analysis demonstrates the performance improvements of GA-based ensemble method are statistically significant. Conclusions: The proposed method is a promising tool for predicting the immunogenic epitopes. The source codes and datasets are available in . [ABSTRACT FROM AUTHOR]
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- 2015
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232. TAGLN2 regulates T cell activation by stabilizing the actin cytoskeleton at the immunological synapse.
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Bo-Ra Na, Hye-Ran Kim, Piragyte, Indre, Hyun-Mee Oh, Min-Sung Kwon, Akber, Uroos, Hyun-Su Lee, Do-Sim Park, Woo Keun Song, Zee-Yong Park, Sin-Hyeog Im, Mun-Chual Rho, Young-Min Hyun, Minsoo Kim, and Chang-Duk Jun
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T cells , *CYTOSKELETON , *SYNAPSES , *NERVE endings , *ACTIN research , *LEUCOCYTES - Abstract
The formation of an immunological synapse (IS) requires tight regulation of actin dynamics by many actin polymerizing/depolymerizing proteins. However, the significance of actin stabilization at the IS remains largely unknown. In this paper, we identify a novel function of TAGLN2--an actin-binding protein predominantly expressed in T cells--in stabilizing cortical F-actin, thereby maintaining F-actin contents at the IS and acquiring LFA-1 (leukocyte function-associated antigen-1) activation after T cell receptor stimulation. TAGLN2 blocks actin depolymerization and competes with cofilin both in vitro and in vivo. Knockout of TAGLN2 (TAGLN2-/-) reduced F-actin content and destabilized F-actin ring formation, resulting in decreased cell adhesion and spreading. TAGLN2-/- T cells displayed weakened cytokine production and cytotoxic effector function. These findings reveal a novel function of TAGLN2 in enhancing T cell responses by controlling actin stability at the IS. [ABSTRACT FROM AUTHOR]
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- 2015
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233. Mesenchymal stem cells are enriched in head neck squamous cell carcinoma, correlates with tumour size and inhibit T-cell proliferation.
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Liotta, F, Querci, V, Mannelli, G, Santarlasci, V, Maggi, L, Capone, M, Rossi, M C, Mazzoni, A, Cosmi, L, Romagnani, S, Maggi, E, Gallo, O, and Annunziato, F
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MESENCHYMAL stem cells , *HEAD & neck cancer , *SQUAMOUS cell carcinoma , *T cells , *CELL proliferation - Abstract
Background:Cancer is a multifactorial disease not only restricted to transformed epithelium, but also involving cells of the immune system and cells of mesenchymal origin, particularly mesenchymal stem cells (MSCs). Mesenchymal stem cells contribute to blood- and lymph- neoangiogenesis, generate myofibroblasts, with pro-invasive activity and may suppress anti-tumour immunity.Methods:In this paper, we evaluated the presence and features of MSCs isolated from human head neck squamous cell carcinoma (HNSCC).Results:Fresh specimens of HNSCC showed higher proportions of CD90+ cells compared with normal tissue; these cells co-expressed CD29, CD105, and CD73, but not CD31, CD45, CD133, and human epithelial antigen similarly to bone marrow-derived MSCs (BM-MSCs). Adherent stromal cells isolated from tumour shared also differentiation potential with BM-MSCs, thus we named them as tumour-MSCs. Interestingly, tumour-MSCs showed a clear immunosuppressive activity on in vitro stimulated T lymphocytes, mainly mediated by indoelamine 2,3 dioxygenase activity, like BM-MSCs. To evaluate their possible role in tumour growth in vivo, we correlated tumour-MSC proportions with neoplasm size. Tumour-MSCs frequency directly correlated with tumour volume and inversely with the frequency of tumour-infiltrating leukocytes.Conclusions:These data support the concept that tumour-MSCs may favour tumour growth not only through their effect on stromal development, but also by inhibiting the anti-tumour immune response. [ABSTRACT FROM AUTHOR]
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- 2015
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234. Mannose 6 phosphorylation of lysosomal enzymes controls B cell functions.
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Otorno, Takanobu, Schweizer, Michaela, Kollmann, Katrin, Schumacher, Valéa, Muschol, Nicole, Tolosa, Eva, Mittrücker, Hans-Willi, and Braulke, Thomas
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ANTIGEN analysis , *LYSOSOMES , *B cells , *DENDRITIC cells , *T cells - Abstract
Antigen processing and presentation and cytotoxic targeting depend on the activities of several lysosomal enzymes that require mannose 6-phosphate (M6P) sorting signals for efficient intracellular transport and localization. In this paper, we show that mice deficient in the formation of M6P residues exhibit significant loss of cathepsin proteases in B cells, leading to lysosomal dysfunction with accumulation of storage material, impaired antigen processing and presentation, and subsequent defects in B cell maturation and antibody production. The targeting of lysosomal and granular enzymes lacking M6P residues is less affected in dendritic cells and T cells and sufficient for maintenance of degradative and lytic functions. M6P deficiency also impairs serum immunoglobulin levels and antibody responses to vaccination in patients. Our data demonstrate the critical role of M6P-dependent transport routes for B cell functions in vivo and humoral immunity in mice and human. [ABSTRACT FROM AUTHOR]
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- 2015
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235. Receptor Binding Domain Based HIV Vaccines.
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Liu, Huan, Bi, Wenwen, Wang, Qian, Lu, Lu, and Jiang, Shibo
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AIDS vaccines , *CELL receptors , *HIV , *IMMUNITY , *IMMUNOGLOBULINS , *GENETIC mutation , *PROTEINS , *T cells , *CD4 antigen , *DRUG development , *MEMBRANE glycoproteins - Abstract
This paper analyzes the main trend of the development of acquired immunodeficiency syndrome (AIDS) vaccines in recent years. Designing an HIV-1 vaccine that provides robust protection from HIV-1 infection remains a challenge despite many years of effort. Therefore, we describe the receptor binding domain of gp120 as a target for developing AIDS vaccines. And we recommend some measures that could induce efficiently and produce cross-reactive neutralizing antibodies with high binding affinity. Those measures may offer a new way of the research and development of the potent and broad AIDS vaccines. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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236. Naturally Occurring Anthraquinones: Chemistry and Therapeutic Potential in Autoimmune Diabetes.
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Shih-Chang Chien, Yueh-Chen Wu, Zeng-Weng Chen, and Wen-Chin Yang
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LEUCOCYTES , *T cells , *TREATMENT of diabetes , *ALTERNATIVE medicine , *ANTI-inflammatory agents , *CELL physiology , *CELL receptors , *PHYSICAL & theoretical chemistry , *CHEMOKINES , *HYPOGLYCEMIC agents , *TYPE 1 diabetes , *MEDICINAL plants , *PROTEIN kinases , *QUINONE , *PLANT extracts , *CELL migration inhibition , *PHYSIOLOGY - Abstract
Anthraquinones are a class of aromatic compounds with a 9,10-dioxoanthracene core. So far, 79 naturally occurring anthraquinones have been identified which include emodin, physcion, cascarin, catenarin, and rhein. A large body of literature has demonstrated that the naturally occurring anthraquinones possess a broad spectrum of bioactivities, such as cathartic, anticancer, antiinflammatory, antimicrobial, diuretic, vasorelaxing, and phytoestrogen activities, suggesting their possible clinical application in many diseases. Despite the advances that have been made in understanding the chemistry and biology of the anthraquinones in recent years, research into their mechanisms of action and therapeutic potential in autoimmune disorders is still at an early stage. In this paper, we briefly introduce the etiology of autoimmune diabetes, an autoimmune disorder that affects as many as 10 million worldwide, and the role of chemotaxis in autoimmune diabetes. We then outline the chemical structure and biological properties of the naturally occurring anthraquinones and their derivatives with an emphasis on recent findings about their immune regulation. We discuss the structure and activity relationship, mode of action, and therapeutic potential of the anthraquinones in autoimmune diabetes, including a new strategy for the use of the anthraquinones in autoimmune diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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237. Global stability and periodic oscillations for an SIV infection model with immune response and intracellular delays.
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Song, Haitao, Liu, Shengqiang, Jiang, Weihua, and Wang, Jinliang
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SIMIAN immunodeficiency virus , *IMMUNE response , *T cells , *CYTOTOXIC T cells , *HOPF bifurcations - Abstract
In this paper, we consider the combined effects of cytotoxic T lymphocyte (CTL) responses on the competition dynamics of two Simian immunodeficiency virus (SIV) strains model. One of strains concerns a relatively slowly replicating and mildly cytopathic virus in the early infection (SIVMneCL8), the other is faster replicating and more cytopathic virus at later stages of the infection (SIVMne170). It is shown that the global dynamics of the ordinary differential equations can be determined by several threshold parameters, and we prove the global stability of the equilibria by rigorous mathematical analysis. To account for a series of infection mechanism leading to viral production, we incorporate time delays in the infection term. Using the methods of constructing suitable Lyapunov functionals and LaSalle’s invariance principle, we obtain the sufficient conditions for the global attractiveness of infection-free equilibrium with both virus strains going extinct, single-infection equilibrium with one of two virus strains out-competing the other one and the two strains coexisting infection equilibrium. We establish that the intracellular delays can destabilize the single-infection equilibrium leading to Hopf bifurcation and periodic oscillations. We show that introduction of immune responses is responsible for the coexistence of two virus strains and the intracellular delays may alter the two-strain competition results. Numerical simulations are presented to illustrate the theoretical conclusions. [ABSTRACT FROM AUTHOR]
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- 2014
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238. Gliadin Peptides as Triggers of the Proliferative and Stress/Innate Immune Response of the Celiac Small Intestinal Mucosa.
- Author
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Barone, Maria Vittoria, Troncone, Riccardo, and Auricchio, Salvatore
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CELIAC disease treatment , *EPIDERMAL growth factor , *IMMUNE response , *INTERLEUKIN-15 , *T cells , *GLIADINS - Abstract
Celiac disease (CD) is a frequent inflammatory intestinal disease, with a genetic background, caused by gliadin-containing food. Undigested gliadin peptides induce innate and adaptive T cell-mediated immune responses. The major mediator of the stress and innate immune response to gliadin peptides (i.e., peptide 31-43, P31-43) is the cytokine interleukin-15 (IL-15). The role of epithelial growth factor (EGF) as a mediator of enterocyte proliferation and the innate immune response has been described. In this paper, we review the most recent literature on the mechanisms responsible for triggering the up-regulation of these mediators in CD by gliadin peptides. We will discuss the role of P31-43 in enterocyte proliferation, structural changes and the innate immune response in CD mucosa in cooperation with EGF and IL-15, and the mechanism of up-regulation of these mediators related to vesicular trafficking. We will also review the literature that focuses on constitutive alterations of the structure, signalling/proliferation and stress/innate immunity pathways of CD cells. Finally, we will discuss how these pathways can be triggered by gliadin peptide P31-43 in controls, mimicking the celiac cellular phenotype. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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239. Global analysis of HIV-1 dynamics with Hill type infection rate and intracellular delay.
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Bairagi, N. and Adak, D.
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HIV infections , *GLOBAL analysis (Mathematics) , *VIRAL transmission , *ENDEMIC diseases , *T cells - Abstract
The mass action infection law, the most frequently used transmission process in the theoretical studies of disease dynamics, has been challenged in various ways. Hill type infection rate is supposed to be a better alternative to mass action law. In the first phase of this paper, we study a basic HIV model with Hill type infection rate. In the second phase, we modify our basic model with intracellular delay τ that measures the time between the first effective contact between a virus and a healthy CD4 + T cell and the latter becomes productively infective. Mathematical results like well-posedness, permanence, local stability and global stability of both the delayed and non-delayed systems are studied. It is observed that the endemic equilibrium is locally and globally asymptotically stable if the virus replication factor is greater than a threshold value and unstable otherwise. In the latter case, the disease-free steady state occurs and is proved to be globally asymptotically stable. Our simulation results shed different insights on drug therapy when various perturbations are given to the system. It is shown that multi-blockers drug therapy is more appropriate in the treatment of HIV patients in comparison to any mono-blocker drug therapy. [ABSTRACT FROM AUTHOR]
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- 2014
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240. Characteristics of the somatic hypermutation in the Camelus dromedarius T cell receptor gamma (TRG) and delta (TRD) variable domains.
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Ciccarese, Salvatrice, Vaccarelli, Giovanna, Lefranc, Marie-Paule, Tasco, Gianluca, Consiglio, Arianna, Casadio, Rita, Linguiti, Giovanna, and Antonacci, Rachele
- Subjects
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GENETIC mutation , *SOMATIC cells , *CAMELS , *T cells , *CELL receptors - Abstract
In previous reports, we had shown in Camelus dromedarius that diversity in T cell receptor gamma (TRG) and delta (TRD) variable domains can be generated by somatic hypermutation (SHM). In the present paper, we further the previous finding by analyzing 85 unique spleen cDNA sequences encoding a total of 331 mutations from a single animal, and comparing the properties of the mutation profiles of dromedary TRG and TRD variable domains. The transition preference and the significant mutation frequency in the AID motifs (dgyw/wrch and wa/tw) demonstrate a strong dependence of the enzymes mediating SHM in TRG and TRD genes of dromedary similar to that of immunoglobulin genes in mammals. Overall, results reveal no asymmetry in the motifs targeting, i.e. mutations are equally distributed among g:c and a:t base pairs and replacement mutations are favored at the AID motifs, whereas neutral mutations appear to be more prone to accumulate in bases outside of the motifs. A detailed analysis of clonal lineages in TRG and TRD cDNA sequences also suggests that clonal expansion of mutated productive rearrangements may be crucial in shaping the somatic diversification in the dromedary. This is confirmed by the fact that our structural models, computed by adopting a comparative procedure, are consistent with the possibility that, irrespective of where (in the CDR-IMGT or in FR-IMGT) the diversity was generated by mutations, both clonal expansion and selection seem to be strictly related to an enhanced structural stability of the γδ subunits. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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241. A Mouse Strain Defective in Both T Cells and NK Cells Has Enhanced Sensitivity to Tumor Induction by Plasmid DNA Expressing Both Activated H-Ras and c-Myc.
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Sheng-Fowler, Li, Tu, Wei, Fu, Haiqing, Murata, Haruhiko, Lanning, Lynda, Foseh, Gideon, Macauley, Juliete, Blair, Donald, Hughes, Stephen H., Coffin, John M., Lewis Jr, Andrew M., and Peden, Keith
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T cells , *TUMORS , *PLASMIDS , *TRANSGENIC mice , *MICROBIAL sensitivity tests , *ONCOGENES - Abstract
As part of safety studies to evaluate the risk of residual cellular DNA in vaccines manufactured in tumorigenic cells, we have been developing in vivo assays to detect and quantify the oncogenic activity of DNA. We generated a plasmid expressing both an activated human H-ras gene and murine c-myc gene and showed that 1 µg of this plasmid, pMSV-T24-H-ras/MSV-c-myc, was capable of inducing tumors in newborn NIH Swiss mice. However, to be able to detect the oncogenicity of dominant activated oncogenes in cellular DNA, a more sensitive system was needed. In this paper, we demonstrate that the newborn CD3 epsilon transgenic mouse, which is defective in both T-cell and NK-cell functions, can detect the oncogenic activity of 25 ng of the circular form of pMSV-T24-H-ras/MSV-c-myc. When this plasmid was inoculated as linear DNA, amounts of DNA as low as 800 pg were capable of inducing tumors. Animals were found that had multiple tumors, and these tumors were independent and likely clonal. These results demonstrate that the newborn CD3 epsilon mouse is highly sensitive for the detection of oncogenic activity of DNA. To determine whether it can detect the oncogenic activity of cellular DNA derived from four human tumor-cell lines (HeLa, A549, HT-1080, and CEM), DNA (100 µg) was inoculated into newborn CD3 epsilon mice both in the presence of 1 µg of linear pMSV-T24-H-ras/MSV-c-myc as positive control and in its absence. While tumors were induced in 100% of mice with the positive-control plasmid, no tumors were induced in mice receiving any of the tumor DNAs alone. These results demonstrate that detection of oncogenes in cellular DNA derived from four human tumor-derived cell lines in this mouse system was not possible; the results also show the importance of including a positive-control plasmid to detect inhibitory effects of the cellular DNA. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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242. Molecular characterization and expression of CD2BP2 in Nile tilapia (Oreochromis niloticus) in response to Streptococcus agalactiae stimulus.
- Author
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Zhen Gan, Bei Wang, Yishan Lu, Shuanghu Cai, Jia Cai, JiChang Jian, and Zaohe Wu
- Subjects
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GENE expression , *MOLECULAR genetics , *NILE tilapia , *STREPTOCOCCUS agalactiae , *CARRIER proteins , *CD2 antigen , *T cells , *RNA splicing - Abstract
CD2BP2 (CD2 cytoplasmic tail binding protein 2), one of several proteins interacting with the cytoplasmic tail of CD2, plays a crucial role in CD2-triggered T cell activation and nuclear splicing. The studies on CD2BP2 have tended to be confined to a few mammals, and little information is available to date regarding fish CD2BP2. In this paper, a CD2BP2 gene (On-CD2BP2) was cloned from Nile tilapia, Oreochromis niloticus. Sequence analysis showed that the full length of On-CD2BP2 cDNA was 1429 bp, containing a 5'untranslated region (UTR) of 111 bp, a 3'-UTR of 193 bp and an open reading frame of 1125 bp which is encoding 374 amino acids. Two important structural features, a GYF domain and a consensus motif GPFXXXXMXXWXXXGYF were detected in the deduced amino acid sequence of On-CD2BP2, and the deduced genomic structure of On-CD2BP2 was similar to the known CD2BP2. The mRNA expression of On-CD2BP2 in various tissues of Nile tilapia was analyzed by fluorescent quantitative real-time PCR. In healthy Nile tilapia, the On-CD2BP2 transcripts were mainly detected in the head kidney and spleen. While vaccinated with inactivated Streptococcus agalactiae, the On-CD2BP2 mRNA expression was significantly up-regulated in the head kidney, spleen and brain 48 h post immunization. Moreover, there was a clear time-dependent expression pattern of On-CD2BP2 after immunization and the expression reached the highest level at 24 h in the brain and 48 h in the head kidney and spleen. This is the first report of proving the presence of a CD2BP2 ortholog in fish, and investigating its tissue distribution and expression profile in response to bacterial stimulus. These findings indicated that On-CD2BP2 may play an important role in the immune response to bacteria in Nile tilapia. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
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243. Interleukin-17 in human inflammatory diseases.
- Author
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Shabgah, Arezoo Gowhari, Fattahi, Ebrahim, and Shahneh, Fatemeh Zare
- Subjects
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INTERLEUKIN-17 , *INFLAMMATION , *TUMOR necrosis factors , *CYTOKINES , *AUTOIMMUNE diseases , *ENDOTHELIAL cells , *RHEUMATOID arthritis - Abstract
Human Th17 pro-inflammatory cells are currently defined as cells that produce IL-17A and F, tumor necrosis factor (TNF)-a, IL-6, IL-21, IL-22 and IL-23. Recently discovered related molecules are forming a family of cytokines, the IL-17 family, IL-17A, IL-17B, IL-17C, IL-17D, IL-17E and IL-17F . The associated receptors for the IL-17 family identified are IL-17R, IL-17RH1, IL-17RL (receptor like), IL-17RD and IL-17RE. This review introduces the roles of IL-17 and Th17 cells in human autoimmune diseases. Studies have shown that T cells with inflammatory effects on epithelial, endothelial and fibroblast cells express IL-17. Th17 cells are supposed to be involved in various autoimmune diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis, and inflammatory bowel diseases. Base on the biologic functions and regulation, IL-17 has regulatory roles in host defense and chronic inflammation which result in tissue damage and autoimmunity. So the IL-17 links links innate and adaptive immunity and has both beneficial and pathological effects on the immune system. This paper will focus on the possible roles of IL-17 in autoimmune diseases, a fundamental player in immune regulation. [ABSTRACT FROM AUTHOR]
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- 2014
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244. Quantitative Analysis of the Processes and Signaling Events Involved in Early HIV-1 Infection of T Cells.
- Author
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Santos, Guido, Valenzuela-Fernández, Agustín, and Torres, Néstor V.
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HIV infections , *T cells , *CELLULAR signal transduction , *LYMPHOCYTES , *VIRAL receptors , *NUCLEATION , *PHYSIOLOGY - Abstract
Lymphocyte invasion by HIV-1 is a complex, highly regulated process involving many different types of molecules that is prompted by the virus's association with viral receptors located at the cell-surface membrane that culminates in the formation of a fusion pore through which the virus enters the cell. A great deal of work has been done to identify the key actors in the process and determine the regulatory interactions; however, there have been no reports to date of attempts being made to fully understand the system dynamics through a systemic, quantitative modeling approach. In this paper, we introduce a dynamic mathematical model that integrates the available information on the molecular events involved in lymphocyte invasion. Our model shows that moesin activation is induced by virus signaling, while filamin-A is mobilized by the receptor capping. Actin disaggregation from the cap is facilitated by cofilin. Cofilin is inactivated by HIV-1 signaling in activated lymphocytes, while in resting lymphocytes another signal is required to activate cofilin in the later stages in order to accelerate the decay of the aggregated actin as a restriction factor for the viral entry. Furthermore, stopping the activation signaling of moesin is sufficient to liberate the actin filaments from the cap. The model also shows the positive effect of gelsolin on actin capping by means of the nucleation effect. These findings allow us to propose novel approaches in the search for new therapeutic strategies. In particular, gelsolin inhibition is seen as a promising target for preventing HIV-1 entry into lymphocytes, due to its role in facilitating the capping needed for the invasion. Also it is shown that HIV-1 should overcome the cortical actin barrier during early infection and predicts the different susceptibility of CD4+ T cells to be infected in terms of actin cytoskeleton dynamics driven by associated cellular factors. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
245. Author Correction: CD8+ T cell activation by murine erythroblasts infected with malaria parasites.
- Author
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Imai, Takashi, Ishida, Hidekazu, Suzue, Kazutomo, Hirai, Makoto, Taniguchi, Tomoyo, Okada, Hiroko, Suzuki, Tomohisa, Shimokawa, Chikako, and Hisaeda, Hajime
- Subjects
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PLASMODIUM , *T cells - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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- View/download PDF
246. The Mysterious Actor—γδ T Lymphocytes in Chronic Lymphocytic Leukaemia (CLL).
- Author
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Zarobkiewicz, Michał K. and Bojarska-Junak, Agnieszka A.
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CHRONIC leukemia , *LYMPHOCYTIC leukemia , *CHRONIC lymphocytic leukemia , *T cells , *B cells , *CYTOTOXIC T cells , *LEUKEMIA - Abstract
Chronic lymphocytic leukaemia (CLL) is the most common leukaemia among adults. It is the clonal expansion of B cells expressing CD19 and CD5. Despite significant progress in treatment, CLL is still incurable. γδ T cells comprise an important subset of the cytotoxic T cells. Although γδ T cells in CLL are dysfunctional, they still can possibly be used for immunotherapy. The current paper reviews our understanding of γδ T lymphocytes in CLL. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
247. The Human Microbiota and Skin Cancer.
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Woo, Yu Ri, Cho, Sang Hyun, Lee, Jeong Deuk, and Kim, Hei Sung
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SKIN cancer , *HUMAN microbiota , *SKIN diseases , *ATOPIC dermatitis , *T cells - Abstract
Skin cancer is the most common type of cancer in the US with an increasing prevalence worldwide. While ultraviolet (UV) radiation is a well-known risk factor, there is emerging evidence that the microbiota may also contribute. In recent years, the human microbiota has become a topic of great interest, and its association with inflammatory skin diseases (i.e., atopic dermatitis, acne, rosacea) has been explored. Little is known of the role of microbiota in skin cancer, but with the recognized link between microbial dysbiosis and inflammation, and knowledge that microbiota modulates the effect of UV-induced immunosuppression, theories connecting the two have surfaced. In this paper, we provide a comprehensive review of the key literature on human microbiota, especially the skin microbiota, and skin cancer (i.e., non-melanoma skin cancer, melanoma, cutaneous T cell lymphoma). Also, mechanistic perspectives as to how our microbiota influence skin cancer development and treatment are offered. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
248. The Organization of the Pig T-Cell Receptor γ (TRG) Locus Provides Insights into the Evolutionary Patterns of the TRG Genes across Cetartiodactyla.
- Author
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Linguiti, Giovanna, Giannico, Francesco, D'Addabbo, Pietro, Pala, Angela, Caputi Jambrenghi, Anna, Ciccarese, Salvatrice, Massari, Serafina, and Antonacci, Rachele
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LOCUS (Genetics) , *T cells , *GENES , *SWINE , *WILD boar - Abstract
The domestic pig (Sus scrofa) is a species representative of the Suina, one of the four suborders within Cetartiodactyla. In this paper, we reported our analysis of the pig TRG locus in comparison with the loci of species representative of the Ruminantia, Tylopoda, and Cetacea suborders. The pig TRG genomic structure reiterates the peculiarity of the organization of Cetartiodactyla loci in TRGC "cassettes", each containing the basic V-J-J-C unit. Eighteen genes arranged in four TRGC cassettes, form the pig TRG locus. All the functional TRG genes were expressed, and the TRGV genes preferentially rearrange with the TRGJ genes within their own cassette, which correlates the diversity of the γ-chain repertoire with the number of cassettes. Among them, the TRGC5, located at the 5′ end of the locus, is the only cassette that retains a marked homology with the corresponding TRGC cassettes of all the analyzed species. The preservation of the TRGC5 cassette for such a long evolutionary time presumes a highly specialized function of its genes, which could be essential for the survival of species. Therefore, the maintenance of this cassette in pigs confirms that it is the most evolutionarily ancient within Cetartiodactyla, and it has undergone a process of duplication to give rise to the other TRGC cassettes in the different artiodactyl species in a lineage-specific manner. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
249. Editorial: anti-tumour necrosis factor α antibodies - can efficacy be regained?
- Author
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Bar‐Yoseph, H. and Chowers, Y.
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ANTINEOPLASTIC agents , *TUMOR necrosis factors , *IMMUNOGLOBULINS , *T cells , *INFLAMMATORY bowel diseases , *ADALIMUMAB , *INFLIXIMAB , *THERAPEUTICS - Abstract
Linked Content This article is linked to Strik et al and Strik, D'Heans papers. To view these articles visit https://doi.org/10.1111/apt.13994 and https://doi.org/10.1111/apt.14071. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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250. Mathematical Modeling of Interleukin-27 Induction of Anti-Tumor T Cells Response.
- Author
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Liao, Kang-Ling, Bai, Xue-Feng, and Friedman, Avner
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INTERLEUKIN-27 , *ANTINEOPLASTIC agents , *T cells , *DEVELOPMENTAL biology , *CYTOKINES , *IMMUNOREGULATION - Abstract
Interleukin-12 is a pro-inflammatory cytokine which promotes Th1 and cytotoxic T lymphocyte activities, such as Interferon- secretion. For this reason Interleukin-12 could be a powerful therapeutic agent for cancer treatment. However, Interleukin-12 is also excessively toxic. Interleukin-27 is an immunoregulatory cytokine from the Interleukin-12 family, but it is not as toxic as Interleukin-12. In recent years, Interleukin-27 has been considered as a potential anti-tumor agent. Recent experiments in vitro and in vivo have shown that cancer cells transfected with IL-27 activate CD8+ T cells to promote the secretion of anti-tumor cytokines Interleukin-10, although, at the same time, IL-27 inhibits the secretion of Interferon- by CD8+ T cells. In the present paper we develop a mathematical model based on these experimental results. The model involves a dynamic network which includes tumor cells, CD8+ T cells and cytokines Interleukin-27, Interleukin-10 and Interferon-. Simulations of the model show how Interleukin-27 promotes CD8+ T cells to secrete Interleukin-10 to inhibit tumor growth. On the other hand Interleukin-27 inhibits the secretion of Interferon- by CD8+ T cells which somewhat diminishes the inhibition of tumor growth. Our numerical results are in qualitative agreement with experimental data. We use the model to design protocols of IL-27 injections for the treatment of cancer and find that, for some special types of cancer, with a fixed total amount of drug, within a certain range, continuous injection has better efficacy than intermittent injections in reducing the tumor load while the treatment is ongoing, although the decrease in tumor load is only temporary. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
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