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Cellular Immunology

Rong Tang, Wallace Y Langdon, Jian Zhang
Casitas B lymphoma-b (Cbl-b), a RING finger E3 ubiquitin ligase, has been identified as a critical regulator of adaptive immune responses. Cbl-b is essential for establishing the threshold for T cell activation and regulating peripheral T cell tolerance through various mechanisms. Intriguingly, recent studies indicate that Cbl-b also modulates innate immune responses, and plays a key role in host defense to pathogens and anti-tumor immunity. These studies suggest that targeting Cbl-b may represent a potential therapeutic strategy for the management of human immune-related disorders such as autoimmune diseases, infections, tumors, and allergic airway inflammation...
November 7, 2018: Cellular Immunology
Gabriele Blahnik, Hannes Uchtenhagen, I-Ting Chow, Cate Speake, Carla Greenbaum, William W Kwok, Eddie A James
CD4+ T cell responses are thought to play a role in type 1 diabetes (T1D). However, detection and characterization of T cells that respond to beta cell epitopes in subjects with T1D has been limited by technical obstacles, including the inherently low frequencies in peripheral blood and variable responsiveness of individual subjects to single epitopes. We implemented a multicolor staining approach that allows direct ex vivo characterization of multiple CD4+ T cell specificities in a single sample. Here we demonstrate and apply that multicolor approach to directly measure the frequency and phenotype of beta cell specific CD4+ T cells in T1D patients and HLA matched controls...
November 7, 2018: Cellular Immunology
Ana Valério-Bolas, Maria Pereira, Graça Alexandre-Pires, David Santos-Mateus, Armanda Rodrigues, Mariana Rafael-Fernandes, Aurea Gabriel, Felipe Passero, Gabriela Santos-Gomes
Neutrophils are short-lived phagocytic cells equipped with several receptors for pathogen recognition and phagocytosis and have intracellular and extracellular effector mechanisms that can inactivate pathogens. Leishmaniases are diseases caused by different species of Leishmania that mainly afflicts poorer populations of tropical and subtropical regions and immunocompromised individuals. Thus, the present study aims to investigate the effector response of murine neutrophils to species of Leishmania causing American cutaneous leishmaniasis and zoonotic visceral leishmaniasis by evaluating pattern recognition receptors (PRR) and intracellular and extracellular effector microbicide activity...
November 7, 2018: Cellular Immunology
Umeshkumar Vekariya, Kavita Rawat, Reshu Saxena, Raj Kamal Tripathi
POTE is known as cancer antigen, expressed in many cancers, along with very few normal tissues like prostate, ovary, testes and embryo. Till date, POTEE identified as majorly expressed POTE paralog. Functionally, POTEF regulates TLR signaling which play important role in innate immunity provided clue about expression of POTE in immune cells. We have chosen three Thp1monocytes, Jurkat T1 and MΦ cells as a model. Here, first time we report expression of POTEE in immune cells specifically only in MΦ but not in monocytes or T-cells...
November 3, 2018: Cellular Immunology
Witida Laopajon, Supansa Pata, Nuchjira Takheaw, Sirirat Surinkaew, Saichit Khummuang, Watchara Kasinrerk
CD99, a leukocyte surface glycoprotein, has been implicated in many cellular processes including cell adhesion, cell migration and T cell activation. Our previous study demonstrated the anti-CD99 monoclonal antibody (mAb) clone MT99/3 inhibited T cell activation; however, the mechanism is unclear. In this study, we demonstrated that CD99 expressed on monocytes played a role in the inhibition of T cell activation. Anti-CD99 mAb MT99/3 downregulated the expression of costimulatory molecule CD86, but upregulated IL-6, IL-10 and TNF-α production by monocytes...
November 2, 2018: Cellular Immunology
Chunlei Li, Baobao Song, Patricia M Santos, Lisa H Butterfield
Alpha fetoprotein (AFP) is produced by over 50% of hepatocellular carcinomas (HCC). Uptake of tumor-derived AFP (tAFP) can impair activity of human dendritic cells (DC). The expression pattern of the lipid antigen presenting genes from the CD1 family is reduced in AFP-treated monocyte-derived DC. Surface CD1 family proteins, particularly CD1d, were reduced in AFP-exposed DC (by both normal cord blood-derived AFP (nAFP) and tAFP). NKT cells recognize lipid antigens presented by CD1d molecules. They play an important role in connecting the innate and adaptive immune systems, and in anti-tumor immunity...
November 1, 2018: Cellular Immunology
Zhen Gong, Zhongmei Kuang, Hui Li, Chunyan Li, Md Kaisar Ali, Fujing Huang, Ping Li, Qiming Li, Xue Huang, Sai Ren, Jiang Li, Jianping Xie
Tuberculosis, caused by Mycobacterium tuberculosis infection, remains a global public health threat. The success of M. tuberculosis largely contributes to its manipulation of host cell fate. The role of M. tuberculosis PE/PPE family effectors in the host destiny was intensively explored. In this study, the role of PPE60 (Rv3478) was characterized by using Rv3478 recombinant M. smegmatis. PPE60 can promote host cell pyroptosis via caspases/NLRP3/gasdermin. The production of pro-inflammatory cytokines, such as IL-1β, IL-6, IL-12p40 and TNF-α was altered by PPE60...
October 30, 2018: Cellular Immunology
Cheng Cui, Xiaohong Tian, Yujun Lin, Min Su, Qingquan Chen, Shao-Yuan Wang, Laijun Lai
Although hematopoietic stem cell transplantation (HSCT) has been widely used in the treatment of many diseases, graft-versus-host disease (GVHD) remains a major complication after allogeneic HSCT. Butyrophilin-like 2 (BTNL2) protein has been reported to have the ability to inhibit T cell proliferation in vitro; its ability to inhibit T cell responses in vivo has not been determined. We show here that in vivo administration of recombinant BTNL2-IgG2a Fc (rBTNL2-Ig) fusion protein ameliorates GVHD in mice. This is related to the ability of rBTNL2-Ig to inhibit T cell proliferation, activation and Th1/Th17 cytokine production in vivo...
October 26, 2018: Cellular Immunology
Jie Shao, Qiuping Xu, Shu Su, Jia Wei, Fanyan Meng, Fangjun Chen, Yang Zhao, Juan Du, Zhengyun Zou, Xiaoping Qian, Baorui Liu
Adoptive immunotherapy is a promising cancer treatment that entails infusion of immune cells manipulated to have antitumor specificity, in vitro. Antigen-specific cytotoxic T lymphocytes are the main executors of transformed cells during cancer immunotherapy. To induce antigen-specific cytotoxic T lymphocytes, we developed artificial antigen-presenting cells (aAPCs) by engineering K562 cells with electroporation to direct the stable expression of HLA-A∗0201, CD80, and 4-1BBL. Our findings demonstrate that after three stimulation cycles, the aAPCs promoted the induction of antigen-specific cytotoxic T lymphocytes with a less differentiated "young" phenotype, which enhanced immune responses with superior cytotoxicity...
October 23, 2018: Cellular Immunology
Diego Alonso, Edgar Serrano, Francisca J Bermejo, Ricardo S Corral
Increasing attention is given to the finding that macrophages under hypoxia are capable of controlling infection by the intracellular protozoan parasite Leishmania amazonensis. The hypoxia-inducible factor (HIF)-1α has been shown to play an essential role in this enhanced innate immune response. Our study aimed to explore the HIF-1α-dependent mechanisms leading to reduced survival of the parasites residing in macrophages under low oxygen conditions. Hypoxia triggered (P < 0.01) NADPH oxidase 2 (Nox2) expression and reactive oxygen species (ROS) production in J774 macrophages upon 24-h infection with L...
October 22, 2018: Cellular Immunology
Eric Marietta, Irina Horwath, Baskar Balakrishnan, Veena Taneja
The role of the intestinal microbiome in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and type 1 diabetes is being increasingly appreciated. Many studies have reported that the compositions of the intestinal microbiomes of patients with these autoimmune diseases are different from those of healthy individuals. Analyses of the intestinal microbiome of humans suggest that various factors affect the composition of the intestinal microbiome, including, but not limited to: geographical location, diet, sex, and age...
October 19, 2018: Cellular Immunology
Barry Paul, Shuqi Kang, Zhihong Zheng, Yubin Kang
Despite significant improvements in the overall survival of patients with multiple myeloma (MM) over the past 15 years, the disease remains incurable. Treatment options are limited for patients who have relapsed or are refractory to immunomodulatory drugs (IMiDs), proteasome inhibitors, and monoclonal antibodies. In these patients, immunotherapies such as checkpoint inhibitors, oncolytic vaccines, and chimeric antigen receptor (CAR) T cells provide a potentially effective alternative treatment. While checkpoint inhibitors are effective in prolonging overall survival in some patients with advanced solid cancers and Hodgkin lymphoma, they have not demonstrated significant activity as a single agent in MM...
October 13, 2018: Cellular Immunology
Mark R Looney, Mark B Headley
The lung represents a unique immune environment. The primary function of the lung is to enable gas exchange by facilitating the transfer of oxygen into and carbon dioxide out of the blood. However, as a direct byproduct of this process the lung is also constantly exposed to particles, allergens, and pathogens alongside air itself. Due to this, the pulmonary immune system exists in a fine balance between quiescence and inflammation, deviations from which can lead to a failure in respiratory function. A rich history exists attempting to define the critical features of lung immunity, and most recently advances in intravital microscopy have enabled the visualization of intercellular immune dynamics in both steady-state and a variety of disease conditions...
October 9, 2018: Cellular Immunology
Tibor Z Veres
The airway mucosa is the primary tissue site exposed to inhaled particulate matter, which includes pathogens and allergens. While most inhaled particles are eliminated from the airways via mucociliary clearance, some pathogens may penetrate the mucosal epithelial barrier and an effective activation of the mucosal immune system is required to prevent further pathogen spread. Similarly, inhaled environmental allergens may induce an aberrant activation of immune cells in the airway mucosa, causing allergic airway disease...
October 3, 2018: Cellular Immunology
Mariana P Lima, Lourena E Costa, Daniela P Lage, Daniel S Dias, Patrícia A F Ribeiro, Amanda S Machado, Fernanda F Ramos, Beatriz C S Salles, Mirian I Fagundes, Gerusa B Carvalho, Michelle L Franklin, Miguel A Chávez-Fumagalli, Ricardo A Machado-de-Ávila, Daniel Menezes-Souza, Mariana C Duarte, Antonio L Teixeira, Denise U Gonçalves, Eduardo A F Coelho
The present study evaluated the cytokine profile in PBMC supernatants and the humoral response in mucosal leishmaniasis (ML) patients and in healthy subjects living in an endemic area. Four proteins, which had previously proven to be antigenic in the human disease, were tested: LiHyM, enolase, eukaryotic initiation factor 5a, and Beta-tubulin. Results showed that all of the proteins stimulated human cells with higher IFN-γ and lower IL-4 and IL-10 levels. The analysis of antibody isotypes correlated with cell response, since the IgG2 production was higher than IgG1 in both groups...
September 28, 2018: Cellular Immunology
Kerstin Renner, Sophia Metz, Anne-Mieke Metzger, Sophia Neumayer, Kathrin Schmidbauer, Yvonne Talke, Simone Buchtler, Dagmar Halbritter, Matthias Mack
A large number of animal models revealed that IL-3 plays an important role for the development of T and B cell-mediated autoimmune diseases. However, little is known about the expression and regulation of IL-3 receptors in human T and B cells and how IL-3 modulates the activation and survival of these cells. We show that the IL-3 receptor CD123 is substantially upregulated on proliferating CD4+ and CD8+ T as well as B cells. Upregulation of CD123 differs between various activators and can be further modulated by cytokines...
September 26, 2018: Cellular Immunology
Saima Naz, Rafiq Ahmad Khan, Jeevan Giddaluru, Srikanth Battu, Sandeep Kumar Vishwakarma, Mabu Subahan, Vishnupriya Satti, Nooruddin Khan, Aleem Ahmed Khan
Ulcerative colitis (UC) is a persistent inflammatory illness, which is clinically categorised as Inflammatory bowel disease (IBD), affecting millions of people worldwide. The precise cause behind the pathology of the disease remains unknown. However, the involvement of multiple factors including genetic predisposition, immunological deregulations, microbiota imbalance, and environmental triggers has been suggested. Amongst all these factors, the over-active immunological response reported in UC patients seems to be a promising target for therapy...
September 21, 2018: Cellular Immunology
Xiaohua Li, Dongchun Liang, Hui Shao, Willi K Born, Henry J Kaplan, Deming Sun
Th17-type autoreactive T cells contribute to pathogenicity in autoimmune diseases, including autoimmune uveitis. However, the mechanisms of regulation of Th17 cell activities remain unsolved and are likely to be tissue- and disease specific. In this review, we have summarized our studies from the murine model of experimental autoimmune uveitis (EAU). The resultsdemonstrate that γδ T cells have a regulatory effect on Th17 response. The regulatory effects of γδ T cells depend on their action state. Activated γδ T cells express significantly high levels of adenosine receptor A2 (A2AR) but low CD73...
September 19, 2018: Cellular Immunology
Bhagirath Singh, Kelly L Summers, Steven M Kerfoot
Pathogenic lymphocytes aberrantly recognize and mount an immune response against self-antigens, leading to the destruction of healthy cells, tissues and organs. Recent studies have shown that both B and T lymphocytes contribute to the development, prevention and modulation of various autoimmune diseases. Regulatory T and B cell subsets appear to play a prominent role in the prevention of autoimmune diseases. The recent identification of novel regulatory Th17 cells, termed as Treg17 cells, has expanded the scope of regulatory T lymphocytes (Treg cells) in the prevention of autoimmune diseases...
September 17, 2018: Cellular Immunology
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