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Delta gamma T-Cells

Yiyang Xu, Zhiyuan Yang, Lucas H Horan, Pengbo Zhang, Lianxing Liu, Bryan Zimdahl, Shon Green, Jingwei Lu, Javier F Morales, David M Barrett, Stephan A Grupp, Vivien W Chan, Hong Liu, Cheng Liu
The clinical use of genetically modified T-cell therapies has led to unprecedented response rates in leukemia and lymphoma patients treated with anti-CD19 chimeric antigen receptor (CAR)-T. Despite this clinical success, FDA-approved T-cell therapies are currently limited to B-cell malignancies, and challenges remain with managing cytokine-related toxicities. We have designed a novel antibody-T-cell receptor (AbTCR) platform where we combined the Fab domain of an antibody with the γ and δ chains of the TCR as the effector domain...
2018: Cell Discovery
Malena M Pérez, Larissa M S Martins, Murilo S Dias, Camila A Pereira, Jefferson A Leite, Enrico C S Gonçalves, Paula Z de Almeida, Emanuelle N de Freitas, Rita C Tostes, Simone G Ramos, Marcel R de Zoete, Bernhard Ryffel, João S Silva, Daniela Carlos
Sound evidence supports a role for interleukin-17 (IL-17)-producing delta-gamma (γδ) T cells and IL-17-producing helper T cells (Th17) in intestinal homeostasis, especially in intestinal barrier integrity. In the present study, we aimed to evaluate the role of IL-17 cytokine in the regulation of intestinal immunity and obesity-induced metabolic syndrome (MetS) in an experimental murine model. C57BL/6 wild-type (WT) mice and mice lacking the IL-17 cytokine receptor (IL-17RA-/- ) were fed either a control diet (CD) or a high-fat diet (HFD) for nine weeks...
November 25, 2018: Immunology
C Suzuki, I Hirai, H Nomura, T Ouchi, M Okayama, S Okamoto, M Amagai, K Tanese, H Takahashi
T cell large granular lymphocyte leukemia (T-LGLL) is a rare chronic lymphoproliferative disorder of mature post-thymic large granular lymphocytes (LGL); either cytotoxic T-lymphocytes or natural killer cells.1 Major phenotype of LGL cells is TCRαβ+CD3+CD4-CD5+CD8+CD27-CD28-CD45-CD57+.2 Less than 10% of cases express TCRγδ instead of TCRαβ.2 Most cases of T-LGLL have an indolent course1 and its cutaneous manifestations have been poorly documented. This article is protected by copyright. All rights reserved...
November 16, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Jenée Mitchell, Egle Kvedaraite, Tatiana von Bahr Greenwood, Jan-Inge Henter, Daniel G Pellicci, Stuart P Berzins, George Kannourakis
Langerhans cell histiocytosis (LCH) lesions are defined by the presence of CD1a+ /CD207+ myeloid cells, but many other immune cells are present including unconventional T cells, which have powerful immunoregulatory functions. Unconventional T cell lineages include mucosal-associated invariant T (MAIT) cells, type I natural killer T (NKT) cells and gamma-delta (γδ) T cells, which are associated with many inflammatory conditions, although their importance has not been studied in LCH. We characterized their phenotype and function in blood and lesions from patients with LCH, and identified a deficiency in MAIT cell frequency and abnormalities in the subset distributions of γδ T cells and NKT cells...
November 7, 2018: Scientific Reports
Hui Pan, Jing Huang, Jun-Nan Li, Li Yang, Jian-Yu Wang, Xin Wang, Lin Liu, Ze-Song Yang, Li Wang
RATIONALE: Hepatosplenic T-cell lymphoma (HSTCL) is a rare but aggressive type of peripheral T-cell lymphoma (PTCL). There is an urgent need for effective treatment due to the poor prognosis of HSTCL. Here, for the 1st time we describe the rare successful case of HSTCL who relapsed after a previous allogeneic stem-cell transplantation (allo-SCT), achieved remission with the second allo-SCT from the same donor. PATIENT CONCERNS: A 24-year-old male, presented with a 2-week history of fever, drenching night sweats and nonquantified weight loss...
November 2018: Medicine (Baltimore)
Amelia R Woolums, Brandi Bourg Karisch, Jane A Parish, Jooyoun Park, Keun Seok Seo, Peres Badial, Steven C Olsen
The effect of a DNA immunostimulant on inflammatory and immune responses, performance, and health in calves following abrupt weaning and introduction to a concentrate diet was tested. Sixty-four single source Angus crossbred steers were weaned on day 1 and assigned to receive a DNA immunostimulant (TRT) or saline (CON) on days 0, 2, 4, and 6. On day 0, steers received clostridial and respiratory vaccines and anthelmintic; they were then transported 2 h, allocated to pens (n = 8 per pen), and introduced to total mixed ration...
October 17, 2018: Journal of Animal Science
Dimpu Gogoi, Dipankar Biswas, Biswajyoti Borkakoty, Jagadish Mahanta
Gamma delta (γδ) T cells exhibit potent anti-Plasmodium activity but are also implicated in the immunopathology of malaria. It is currently poorly understood how γδ T cells are affected in human suffering from Plasmodium vivax infection or in symptomless individuals living in an endemic region. We examined both the percentages and expression of markers associated with immune exhaustion in γδ T cells in individuals living in a P. vivax endemic region by flow cytometry. The percentage of γδ T cells in the blood was significantly higher both in acute P...
December 2018: Parasite Immunology
Jeemin Yim, Seung Geun Song, Sehui Kim, Jae Won Choi, Kyu-Chong Lee, Jeong Mo Bae, Yoon Kyung Jeon
Primary central nervous system lymphoma of T-cell origin (T-PCNSL) is rare, and its clinicopathological features remain unclear. Peripheral T-cell lymphoma (PTCL) of γδ T-cell origin is an aggressive lymphoma mainly involving extranodal sites. Here, we report a case of γδ T-PCNSL involving the intramedullary spinal cord and presenting with paraplegia. A 75-year-old Korean woman visited the hospital complaining of back pain and lower extremity weakness. MRI revealed multifocal enhancing intramedullary nodular lesions in the thoracic and lumbar spinal cord...
October 1, 2018: Journal of Pathology and Translational Medicine
M Watanabe, Makiko Kumagai-Braesch, M Yao, S Thunberg, D Berglund, F Sellberg, C Jorns, S Lind Enoksson, J Henriksson, T Lundgren, M Uhlin, E Berglund, B-G Ericzon
Adoptive transfer of alloantigen-specific immunomodulatory cells generated ex vivo with anti-CD80/CD86 mAbs (2D10.4/IT2.2) holds promise for operational tolerance after transplantation. However, good manufacturing practice is required to allow widespread clinical application. Belatacept, a clinically approved cytotoxic T-lymphocyte antigen 4-immunoglobulin that also binds CD80/CD86, could be an alternative agent for 2D10.4/IT2.2. With the goal of generating an optimal cell treatment with clinically approved reagents, we evaluated the donor-specific immunomodulatory effects of belatacept- and 2D10...
September 27, 2018: Cell Transplantation
Kieran Sahasrabudhe, Mario Otto, Peiman Hematti, Vaishalee Kenkre
Allogeneic hematopoietic stem cell transplantation is a curative option for patients with a variety of diseases. Transplantation from a related haploidentical donor is being increasingly utilized for patients who lack an available human leukocyte antigen matched related or unrelated donor. One of the strategies used for haploidentical transplants involves selective depletion of T cells expressing the αβ T cell receptor and CD19+ B cells prior to transplant. This allows for the removal of cells responsible for graft-versus-host disease and post-transplant lymphoproliferative disorder but maintains hematopoietic progenitor and stem cells for engraftment (CD34+ cells), as well as cells to elicit graft-versus-tumor effect and provide anti-infective activity (such as gamma-delta T cells and natural killer cells)...
September 6, 2018: Leukemia & Lymphoma
Susanne Juhl Pedersen, Walter P Maksymowych
Axial spondyloarthritis (axSpA) is a complex disease that affects the joints and entheses of axial and peripheral joints, and is associated with inflammation in extra-articular sites such as the gut. Improved knowledge on genetics and immunology has improved treatment options with the availability of treatments targeting tumor necrosis factor-α (TNF-α) and interleukin (IL)-17. However, these agents do not provide clinical benefit for about 40% of patients, and additional therapeutic options are necessary...
September 2018: Drugs
Priyanka Devi-Marulkar, Hélène Kaplon, Marie-Caroline Dieu-Nosjean, Myriam Lawand
The tumor microenvironment is a complex network of interacting cells composed of immune and nonimmune cells. It has been reported that the composition of the immune contexture has a significant impact on tumor growth and patient survival in different solid tumors. For instance, we and other groups have previously demonstrated that a strong infiltration of T-helper type 1 (Th1) or memory CD8+ T cells is associated with long-term survival of cancer patients. Nevertheless, the prognostic value of the other immune populations, namely regulatory T cells (Treg), B cells, and gamma delta (γδ) T cells, remains a matter of debate...
2018: Methods in Molecular Biology
Di Wu, Wei-Ming Yan, Hong-Wu Wang, Da Huang, Xiao-Ping Luo, Qin Ning
The mechanisms involved in virus-induced severe hepatitis have not been fully elucidated. In this study, we investigated the role of gamma delta T cell receptors (γδ) T cells in the pathogenesis of fulminant viral hepatitis (FVH) induced by murine hepatitis virus strain 3 (MHV-3). The model of FVH was established by intraperitoneal injection of MHV-3 into Balb/cJ mice. The survival days of mice, and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were examined. The proportions of γδ T cells in blood, spleen and liver, and cytokines secreted by hepatic γδ T cells were analyzed by flow cytometry...
August 2018: Current medical science
Yueshui Zhao, Ling Lin, Zhangang Xiao, Mingxing Li, Xu Wu, Wanping Li, Xiaobing Li, Qijie Zhao, Yuanlin Wu, Hanyu Zhang, Jianhua Yin, Lingling Zhang, Chi Hin Cho, Jing Shen
γδ T cells, a subgroup of T cells based on the γδ TCR, when compared with conventional T cells ( αβ T cells), make up a very small proportion of T cells. However, its various subgroups are widely distributed in different parts of the human body and are attractive effectors for infectious disease immunity. γδ T cells are activated and expanded by nonpeptidic antigens (P-Ags), major histocompatibility complex (MHC) molecules, and lipids which are associated with different kinds of pathogen infections...
2018: Journal of Immunology Research
P C Gaspar, R C M Rudolf-Oliveira, L M Wildner, A C R de Moraes, M L Reis, R M da Silva, J Gonçalves, M L Bazzo, M C Santos-Silva
SETTING: Information about the sputum cells of pulmonary tuberculosis (PTB) patients is scarce. The analysis of sputum cells using optical microscopy (OM) is a well-established method, but it has some serious limitations. OBJECTIVE: To establish a new flow cytometry (FC) protocol for the leucocyte evaluation of sputum samples from PTB patients. DESIGN: A new FC protocol using 0.1% dithiothreitol and 0.5% paraformaldehyde was developed to fluidise sputum samples and kill Mycobacterium tuberculosis, respectively, to allow the analysis of sputum samples collected from TB patients...
September 1, 2018: International Journal of Tuberculosis and Lung Disease
Salma Machan, Raúl Córdoba, Nerea Carvajal, Luis Requena, Miguel Ángel Piris, Fabio Facchetti, Socorro María Rodríguez-Pinilla
Peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS) is a diagnosis of exclusion, showing extreme cytological and phenotypic heterogeneity. Skin involvement of PTCL may be primary or secondary. Diagnosis of histiocytosis may be difficult, requiring clinical-pathological correlation. We describe a laryngeal atypical histiocytic lesion (AHL) and a nasal PTCL, NOS with cutaneous involvement in the same patient presenting with peculiar histopathologic and immunophenotypic features. The laryngeal neoplasm showed morphological and immunophenotypic evidence of histiocytic differentiation and does not fit any other category of the WHO classification nor the revised classification of histiocytosis...
August 6, 2018: American Journal of Dermatopathology
Shohei Iijima, Tomohiro Chiba, Keisuke Maruyama, Kuniaki Saito, Keiichi Kobayashi, Yuki Yamagishi, Junji Shibahara, Nobuyuki Takayama, Yoshiaki Shiokawa, Motoo Nagane
BACKGROUND: Brain involvement of hepatosplenic T cell lymphoma (HSTL) has not been reported so far. CASE DESCRIPTION: We observed an extremely rare case of HSTL, which is a rare and aggressive variant of peripheral T cell lymphoma, generally showing predominant infiltration to the liver, spleen, and bone marrow and involving the brain. A 41-year-old Japanese woman presented with dysarthria and numbness of the right hand. Radiologic examination revealed a single 3-cm mass in the left frontal cortex, which was totally removed...
October 2018: World Neurosurgery
Adrianna M S Laursen, Raveendra R Kulkarni, Khaled Taha-Abdelaziz, Brandon L Plattner, Leah R Read, Shayan Sharif
Immunity against Marek's disease (MD), caused by Gallid herpesvirus 2 (GaHV-2), in chickens is mediated by both innate and adaptive responses. The present study evaluated the effects of GaHV-2 infection on distribution and frequency of γδ T cells in tissues, as well as their expression of cytokines. We found that the infected chickens had significantly higher number of γδ T cells in their spleens by 10 and 21 days post-infection (d.p.i.) and nearly 100% of these γδ T cells were CD8+ at 21 d.p.i. Conversely, the number of γδ T cells in the cecal tonsils of GaHV-2-infected birds decreased compared to uninfected birds...
September 2018: Virology
Jonathan Fisher, John Anderson
Sharing both innate and adaptive immune properties, γδT cells are attractive candidates for cellular engineering. As the cancer immunotherapy field becomes increasingly busy, orthogonal approaches are required to drive advancement. Engineering of alternative effector cell types such as γδT cells represents one such approach. γδT cells can be modified using many of the techniques used in αβT cell engineering, with the added advantage of innate-like tumor recognition and killing. Progress has been made in T-cell receptor transfer to and from γδT cells as well as in a number of chimeric antigen receptor-based strategies...
2018: Frontiers in Immunology
Jeroen Maertzdorf, Mario Tönnies, Laura Lozza, Sandra Schommer-Leitner, Hans Mollenkopf, Torsten T Bauer, Stefan H E Kaufmann
Early immune responses to Mycobacterium tuberculosis (Mtb) invasion of the human lung play a decisive role in the outcome of infection, leading to either rapid clearance of the pathogen or stable infection. Despite their critical impact on health and disease, these early host-pathogen interactions at the primary site of infection are still poorly understood. In vitro studies cannot fully reflect the complexity of the lung architecture and its impact on host-pathogen interactions, while animal models have their own limitations...
2018: Frontiers in Immunology
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