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https://www.readbyqxmd.com/read/29130994/enhancement-of-anti-leukemia-immunity-by-leukemia-derived-exosomes-via-downregulation-of-tgf-%C3%AE-1-expression
#1
Fang Huang, Jiangbo Wan, Weiwei Hu, Siguo Hao
BACKGROUND/AIMS: Minimal residual leukemia cells (MRLs) are difficult to eradicate through traditional treatment and therefore remain to be a major threat to the long-term survival of leukemia patients. Tumor-derived exosomes (TEXs), which carry tumor associated antigens (TAA), may be a potential cell-free tumor vaccine for the specific eradication of MRLs. However, TEXs are intended to be less immunogenic due to exosomal TGF-β1. To further optimize the efficacy of TEX-based vaccines, we investigated whether exosomes from TGF-β1 silenced leukemia cells (LEXTGF-β1si) had an increased potential to induce a specific antitumor effect compared with non-modified exosomes...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29129224/quantification-and-phenotypic-characterisation-of-peripheral-ifn-%C3%AE-producing-leucocytes-in-chickens-vaccinated-against-newcastle-disease
#2
S H Andersen, L Vervelde, K Sutton, L R Norup, E Wattrang, H R Juul-Madsen, T S Dalgaard
The aim of this study was to optimise and evaluate an intracellular cytokine staining (ICS) assay for assessment of T cell IFN-γ responses in chickens vaccinated against Newcastle disease (ND). We aimed to validate currently available antibodies to chicken IFN-γ using transfected CHO cells. Moreover, this ICS assay was evaluated for use to detect mitogen and antigen induced IFN-γ production in chicken peripheral blood leucocytes. Chickens from an inbred white leghorn line containing two MHC haplotypes, B19 and B21, were divided into three experimental groups; one group was kept as naive controls, one group was vaccinated intramuscularly twice with a commercial inactivated ND virus (NDV) vaccine, and the last group was vaccinated orally twice with a commercial live attenuated NDV vaccine...
December 2017: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/29126798/cd4-t-cell-help-confers-a-cytotoxic-t-cell-effector-program-including-coinhibitory-receptor-downregulation-and-increased-tissue-invasiveness
#3
Tomasz Ahrends, Aldo Spanjaard, Bas Pilzecker, Nikolina Bąbała, Astrid Bovens, Yanling Xiao, Heinz Jacobs, Jannie Borst
CD4(+) T cells optimize the cytotoxic T cell (CTL) response in magnitude and quality, by unknown molecular mechanisms. We here present the transcriptomic changes in CTLs resulting from CD4(+) T cell help after anti-cancer vaccination or virus infection. The gene expression signatures revealed that CD4(+) T cell help during priming optimized CTLs in expression of cytotoxic effector molecules and many other functions that ensured efficacy of CTLs throughout their life cycle. Key features included downregulation of PD-1 and other coinhibitory receptors that impede CTL activity, and increased motility and migration capacities...
November 6, 2017: Immunity
https://www.readbyqxmd.com/read/29055517/enhanced-cd8-cytolytic-t-cell-responses-in-the-peripheral-circulation-of-patients-with-sarcoidosis-and-non-l%C3%A3-fgren-s-disease
#4
Venkata Ramanarao Parasa, Helena Forsslund, Tobias Enger, Daniel Lorenz, Susanna Kullberg, Anders Eklund, Magnus Sköld, Jan Wahlström, Johan Grunewald, Susanna Brighenti
BACKGROUND: The role of CD4(+) T cells in the immunopathogenesis of pulmonary sarcoidosis is well-established, while less is known about the phenotype and function of CD8(+) cytolytic T cells (CTLs). METHODS: CD8(+) CTLs were explored in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from up to 25 patients with sarcoidosis and 25 healthy controls. The proportion of CTLs was assessed by the expression of cytolytic effector molecules perforin, granzyme B and granulysin in CD8(+) T cells, using flow cytometry...
October 13, 2017: Respiratory Medicine
https://www.readbyqxmd.com/read/29048978/antitumor-effect-of-oral-cancer-vaccine-with-bifidobacterium-delivering-wt1-protein-to-gut-immune-system-is-superior-to-wt1-peptide-vaccine
#5
Toshiro Shirakawa, Koichi Kitagawa
Despite the revolutionary progress of immune checkpoint inhibitors (CPIs) for cancer immunotherapy, CPIs are effective only in a subset of patients. Combining CPIs and cancer vaccines to achieve better clinical outcomes is a reasonable approach since CPI enhances cancer vaccine-induced tumor-associated antigen (TAA) specific CTL. Among the various TAAs so far identified, WT1 protein is one of the most promising TAAs as a cancer vaccine target. Until now clinical trials of WT1 vaccine have demonstrated only modest clinical efficacy...
October 19, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28979263/cytotoxic-cd4-t-cells-drive-multiple-sclerosis-progression
#6
Liesbet M Peeters, Marjan Vanheusden, Veerle Somers, Bart Van Wijmeersch, Piet Stinissen, Bieke Broux, Niels Hellings
Multiple sclerosis (MS) is the leading cause of chronic neurological disability in young adults. The clinical disease course of MS varies greatly between individuals, with some patients progressing much more rapidly than others, making prognosis almost impossible. We previously discovered that cytotoxic CD4+ T cells (CD4+ CTL), identified by the loss of CD28, are able to migrate to sites of inflammation and that they contribute to tissue damage. Furthermore, in an animal model for MS, we showed that these cells are correlated with inflammation, demyelination, and disability...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28978039/antitumor-immunity-induced-by-ve-cadherin-modified-dc-vaccine
#7
Jing Zhou, Yufeng Xi, Xiyan Mu, Rongce Zhao, Hongdou Chen, Li Zhang, Yang Wu, Qiu Li
Dendritic cells (DCs) are the most potent antigen-presenting cells. A strong interest has been developed in DC vaccines for cancer immunotherapy. Besides, angiogenesis is essential for tumor growth. VE-cadherin has a crucial function in various aspects of vascular biological functions. Here, we produced the full VE-cadherin gene modified DC vaccine (DC-VEC). Its antitumor immunity and chief mechanism driving antitumor effect was evaluated. Analyses were performed including test of antitumor antibody, CTL-mediated cytotoxicity experiment, vascular density, evaluation of the variation of cells and cytokines in immunoregulation...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28932640/co-delivery-of-the-nkt-agonist-%C3%AE-galactosylceramide-and-tumor-antigens-to-cross-priming-dendritic-cells-breaks-tolerance-to-self-antigens-and-promotes-antitumor-responses
#8
Reem Ghinnagow, Julie De Meester, Luis Javier Cruz, Caroline Aspord, Stéphanie Corgnac, Elodie Macho-Fernandez, Daphnée Soulard, Josette Fontaine, Laurence Chaperot, Julie Charles, Fabrice Soncin, Fathia Mami-Chouaib, Joel Plumas, Christelle Faveeuw, François Trottein
Vaccines designed to abrogate the tolerance of tumor self-antigens and amplify cytotoxic CD8(+) T cells (CTLs) have promise for the treatment of cancer. Type I natural killer (NKT) cells have attracted considerable interest in the cancer therapy field. In the current study, we have exploited the unique ability of NKT cells to serve as T-helper cells to license dendritic cells (DCs) for cross priming with the aim to generate efficient CTL antitumor responses. To this end, we designed a nanoparticle-based vaccine to target cross-priming DCs via the Clec9a endocytic pathway...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28887632/multipeptide-coupled-nanoparticles-induce-tolerance-in-humanised-hla-transgenic-mice-and-inhibit-diabetogenic-cd8-t-cell-responses-in-type-1-diabetes
#9
Xinyu Xu, Lingling Bian, Min Shen, Xin Li, Jing Zhu, Shuang Chen, Lei Xiao, Qingqing Zhang, Heng Chen, Kuanfeng Xu, Tao Yang
AIMS/HYPOTHESIS: Induction of antigen-specific immunological tolerance may provide an attractive immunotherapy in the NOD mouse model but the conditions that lead to the successful translation to human type 1 diabetes are limited. In this study, we covalently linked 500 nm carboxylated polystyrene beads (PSB) with a mixture of immunodominant HLA-A*02:01-restricted epitopes (peptides-PSB) that may have high clinical relevance in humans as they promote immune tolerance; we then investigated the effect of the nanoparticle-peptide complexes on T cell tolerance...
December 2017: Diabetologia
https://www.readbyqxmd.com/read/28842467/role-of-lymphocyte-subsets-in-the-immune-response-to-primary-b-cell-derived-exosomes
#10
Sarah C Saunderson, Alexander D McLellan
Exosomes are lipid nanovesicles released after fusion of the endosomal limiting membrane with the plasma membrane. In this study, we investigated the requirement for CD4 T cells, B cells, and NK cells to provide help for CD8 T cell-mediated response to B cell-derived exosomes. CTL responses to Ag-loaded exosomes were dependent on host MHC class I, with a critical role for splenic langerin(+) CD8α(+) dendritic cells (DCs) in exosomal Ag cross-presentation. In addition, there was an absolute dependence on the presence of CD4 T cells, CD8 T cells, and NK cells, where the loss of any one of these subsets led to a complete loss of CTL response...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28841693/the-effect-of-aqueous-extract-of-xinjiang-artemisia-rupestris-l-an-influenza-virus-vaccine-adjuvant-on-enhancing-immune-responses-and-reducing-antigen-dose-required-for-immunity
#11
Ailian Zhang, Danyang Wang, Jinyao Li, Feng Gao, Xucheng Fan
Potent adjuvant can improve the effectiveness of vaccines and reduce the antigen doses required for initiating the protective immunity. In this study, we identified that aqueous extract of Artemisia rupestris L. (AEAR) could be employed as an efficient adjuvant for influenza virus vaccine (V) to enhance immune responses and reduce the antigen doses required for initiating immunity, without compromising the immune response. ICR mice were subcutaneously co-administrated with V combined with different concentrations of AEAR demonstrated that 300 μg AEAR could significantly improve hemagglutination inhibition (HI) and increase IgG antibody titers in serum (P<0...
2017: PloS One
https://www.readbyqxmd.com/read/28833046/ahr-activation-increases-il-2-production-by-alloreactive-cd4-t-cells-initiating-the-differentiation-of-mucosal-homing-tim3-lag3-tr1-cells
#12
Allison K Ehrlich, Jamie M Pennington, Susan Tilton, Xisheng Wang, Nikki B Marshall, Diana Rohlman, Castle Funatake, Sumit Punj, Edmond O'Donnell, Zhen Yu, Siva K Kolluri, Nancy I Kerkvliet
Activation of the aryl hydrocarbon receptor (AhR) by immunosuppressive ligands promotes the development of regulatory T (Treg) cells. Although AhR-induced Foxp3(+) Treg cells have been well studied, much less is known about the development and fate of AhR-induced Type 1 Treg (AhR-Tr1) cells. In the current study, we identified the unique transcriptional and functional changes in murine CD4(+) T cells that accompany the differentiation of AhR-Tr1 cells during the CD4(+) T-cell-dependent phase of an allospecific cytotoxic T lymphocyte (allo-CTL) response...
November 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28810829/blocking-il-10-signalling-at-the-time-of-immunization-does-not-increase-unwanted-side-effects-in-mice
#13
Guoying Ni, Zaowen Liao, Shu Chen, Tianfang Wang, Jianwei Yuan, Xuan Pan, Kate Mounsey, Shelley Cavezza, Xiaosong Liu, Ming Q Wei
BACKGROUND: Cancer therapeutic vaccine induced cytotoxic T cell (CTL) responses are pivotal for the killing of tumour cells. Blocking interleukin 10 (IL-10) signalling at the time of immunization increases vaccine induced CTL responses and improves prevention of tumour growth in animal models compared to immunization without an IL-10 signalling blockade. Therefore, this immunization strategy may have potential to curtail cancer in a clinical setting. However, IL-10 deficiency leads to autoimmune disease in the gut...
August 15, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28798348/fas-ligand-mediated-cytotoxicity-of-cd4-t-cells-during-chronic-retrovirus-infection
#14
Anna Malyshkina, Elisabeth Littwitz-Salomon, Kathrin Sutter, Gennadiy Zelinskyy, Sonja Windmann, Simone Schimmer, Annette Paschen, Hendrik Streeck, Kim J Hasenkrug, Ulf Dittmer
CD4+ helper T cells and cytotoxic CD8+ T cells are key players for adaptive immune responses against acute infections with retroviruses. Similar to textbook knowledge the most important function of CD4+ T cells during an acute retrovirus infection seems to be their helper function for other immune cells. Whereas there was no direct anti-viral activity of CD4+ T cells during acute Friend Virus (FV) infection, they were absolutely required for the control of chronic infection. During chronic FV infection a population of activated FV-specific CD4+ T cells did not express cytotoxic molecules, but Fas Ligand that can induce Fas-induced apoptosis in target cells...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28741237/cytotoxic-t-lymphocytes-and-cd4-epitope-mutations-in-the-pre-core-core-region-of-hepatitis-b-virus-in-chronic-hepatitis-b-carriers-in-northeast-iran
#15
Sareh Zhand, Alijan Tabarraei, Amineh Nazari, Abdolvahab Moradi
BACKGROUNDS: Hepatitis B virus (HBV) is vulnerable to many various mutations. Those within epitopes recognized by sensitized T cells may influence the re-emergence of the virus. This study was designed to investigate the mutation in immune epitope regions of HBV pre-core/core among chronic HBV patients of Golestan province, Northeast Iran. METHODS: In 120 chronic HBV carriers, HBV DNA was extracted from blood plasma samples and PCR was done using specific primers...
July 2017: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
https://www.readbyqxmd.com/read/28739115/a-recombinant-protein-of-salmonella-typhi-induces-humoral-and-cell-mediated-immune-responses-including-memory-responses
#16
Sayan Das, Rimi Chowdhury, Shubhamoy Ghosh, Santasabuj Das
Gram negative enteric bacteria, Salmonella enterica serovar Typhi (S. Typhi), the etiological agent of typhoid fever is a major public health problem in developing countries. While a permanent solution to the problem would require improved sanitation, food and water hygiene, controlling the infection by vaccination is urgently required due to the emergence of multidrug resistant strains in multiple countries. The currently licensed vaccines are moderately efficacious with limited applicability, and no recommended vaccines exist for younger children...
August 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28703774/programmed-cell-death-1-pd-1-and-cytotoxic-t-lymphocyte-associated-antigen-4-ctla-4-in-viral-hepatitis
#17
REVIEW
Hyosun Cho, Hyojeung Kang, Hwan Hee Lee, Chang Wook Kim
Virus-specific cluster of differentiation 8 (CD8+) cytotoxic T cells (CTL) recognize viral antigens presented on major histocompatibility complex (MHC) class I chains on infected hepatocytes, with help from CD4+ T cells. However, this CTL response is frequently weak or undetectable in patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) are receptors in the CD28 family of costimulatory molecules, providing inhibitory signals to T cells...
July 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28666264/antitumor-immunity-induced-by-ve-cadherin-modified-dc-vaccine
#18
Jing Zhou, Yufeng Xi, Xiyan Mu, Rongce Zhao, Hongdou Chen, Li Zhang, Yang Wu, Qiu Li
Dendritic cells (DCs) are the most potent antigen-presenting cells. A strong interest has been developed in DC vaccines for cancer immunotherapy. Besides, angiogenesis is essential for tumor growth. VE-cadherin has a crucial function in various aspects of vascular biological functions. Here, we produced the full VE-cadherin gene modified DC vaccine (DC-VEC). Its antitumor immunity and chief mechanism driving antitumor effect was evaluated. Analyses were performed including test of antitumor antibody, CTL-mediated cytotoxicity experiment, vascular density, evaluation of the variation of cells and cytokines in immunoregulation...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28655469/transcutaneous-immunization-with-a-novel-imiquimod-nanoemulsion-induces-superior-t-cell-responses-and-virus-protection
#19
Pamela Aranda Lopez, Mark Denny, Ann-Kathrin Hartmann, Astrid Alflen, Hans Christian Probst, Esther von Stebut, Stefan Tenzer, Hansjörg Schild, Michael Stassen, Peter Langguth, Markus P Radsak
BACKGROUND: Transcutaneous immunization (TCI) is a novel vaccination strategy utilizing the skin associated lymphatic tissue to induce immune responses. TCI using a cytotoxic T lymphocyte (CTL) epitope and the Toll-like receptor 7 (TLR7) agonist imiquimod mounts strong CTL responses by activation and maturation of skin-derived dendritic cells (DCs) and their migration to lymph nodes. However, TCI based on the commercial formulation Aldara only induces transient CTL responses that needs further improvement for the induction of durable therapeutic immune responses...
June 16, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28601924/tgf-%C3%AE-1-silenced-leukemia-cell-derived-exosomes-target-dendritic-cells-to-induce-potent-anti-leukemic-immunity-in-a-mouse-model
#20
Fang Huang, Jiangbo Wan, Siguo Hao, Xiaohui Deng, Linjun Chen, Liyuan Ma
Tumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from the TGF-β1 silenced L1210 cells (LEXTGF-β1si) can enhance the efficacy of DC-based vaccines. We silenced TGF-β1 in L1210 cells with a lentiviral shRNA vector and prepared the LEXTGF-β1si. It was shown that LEXTGF-β1si can significantly decrease TGF-β1 expression of dendritic cells (DC) and effectively promote their maturation and immune function...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
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