Syh-Jae Lin, Chien-Ya Hsu, Ming-Ling Kuo, Pei-Tzu Lee, Hsiu-Shan Hsiao, Ji-Yih Chen
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and joint destruction. Previous studies have shown that natural killer (NK) cells may play an important role in the pathogenesis of RA. Interleukin (IL)-15, a pro-inflammatory cytokine which induces proliferation and differentiation of NK cells, is overexpressed in RA. In this present study, we examine various NKRs and adhesion molecule expression on NK cells from RA patients and their response to IL-15 stimulation. We also sought to study cytokine-induced memory-like (CIML) NK cells in RA patients...
April 3, 2020: Scientific Reports
Junya Ichikawa, Tatsuya Yoshida, Ariel Isser, Andressa S Laino, Melinda Vassallo, David Woods, Sojung Kim, Mathias Oelke, Kristi Jones, Jonathan P Schneck, Jeffrey S Weber
PURPOSE: Generation of antigen-specific T cells from cancer patients employs large numbers of peripheral blood cells and/or tumor infiltrating cells to generate antigen-presenting and effector cells commonly requiring multiple rounds of re-stimulation ex vivo We used a novel paramagnetic, nanoparticle-based artificial antigen presenting cell (nano-aAPC) that combines anti-CD28 co-stimulatory and human MHC class I molecules that are loaded with antigenic peptides to rapidly expand tumor antigen-specific T cells from melanoma patients...
April 2, 2020: Clinical Cancer Research
Dan Song, Fangfang Qi, ShuaiShuai Liu, Zhongsheng Tang, Jinhai Duan, Zhibin Yao
We previously have reported that neonatal Bacillus Calmette-Guerin (BCG) vaccination improves neurogenesis and behavior in early life through affecting the neuroimmune milieu in the brain, but it is uncertain whether activation phenotypes and functional changes in T lymphocytes shape brain development. Here, we studied the effects of BCG vaccination via the adoptive transfer of T lymphocytes from the BALB/c wild-type mice into naive mice. Our results show that mice adoptive BCG-induced lymphocytes (BCG->naive mice) showed anxiolytic and antidepressant-like performance when completing an elevated plus maze (EPM) test...
2020: PloS One
F N Souza, M G Blagitz, C F Batista, P V Takano, R G Gargano, S A Diniz, M X Silva, J A Ferronatto, K R Santos, M B Heinemann, S De Vliegher, A M M P Della Libera
We analyzed a large number of immune response parameters from quarter milk samples with distinct bacteriological and quarter somatic cell count (qSCC) statuses. Furthermore, we sought to explore and identify displayed immune response patterns in milk samples from mammary glands with nonspecific mastitis. Thus, 92 quarter milk samples from 28 cows were stratified into 4 groups, as follows: (1) 49 culture-negative control quarters with a low qSCC (<1 × 105 cells/mL) from 19 dairy cows (so-called healthy quarters); (2) 15 culture-negative quarters with high qSCC (>2 × 105 cells/mL; so-called quarters with nonspecific mastitis) from 10 dairy cows; (3) 8 culture-positive quarters with low qSCC (noninflammatory quarters with low qSCC) from 5 dairy cows; and (4) 20 culture-positive quarters with high qSCC (so-called truly infected quarters) from 8 dairy cows...
March 27, 2020: Journal of Dairy Science
Junmei Wang, Farah Hasan, Amanda C Frey, Haiyan S Li, Jungsun Park, Ke Pan, Cara Haymaker, Chantale Bernatchez, Dean A Lee, Stephanie S Watowich, Cassian Yee
Clinical response rates after adoptive cell therapy (ACT) are highly correlated with in vivo persistence of the infused T cells. However, antigen-specific T cells found in tumor sites are often well-differentiated effector cells with limited persistence. Central memory CD8+ T cells, capable of self-renewal, represent desirable ACT products. We report here that exposure to a histone deacetylase inhibitor (HDACi) and IL21 could reprogram differentiated human CD8+ T cells into central memory-like T cells. De-differentiation of CD8+ T cells was initiated by increased H3 acetylation and chromatin accessibility at the CD28 promoter region...
March 25, 2020: Cancer Immunology Research
Shima Shahbaz, Garett Dunsmore, Petya Koleva, Lai Xu, Stan Houston, Shokrollah Elahi
We report significant upregulation of Galectin-9 (Gal-9) and VISTA on both CD4+ and CD8+ T cells in HIV-infected human patients. Gal-9 and VISTA expression was associated with impaired T cells effector functions. Although Gal-9 was coexpressed with other coinhibitory receptors such as TIGIT, CD160, CD39, and VISTA, it was simultaneously coexpressed with PD-1. Coexpression of Gal-9 with PD-1 was associated with a more terminally exhausted T cell phenotype in HIV-1 patients. This was marked by higher expression of EOMES, blimp1, and Glut1 in Gal-9+ versus Gal-9- T cells, which is consistent with an exhausted T cell phenotype...
March 23, 2020: Journal of Immunology
F Merah-Mourah, S O Cohen, D Charron, N Mooney, A Haziot
Monocytes contribute to immune responses as a source for subsets of dendritic cells and macrophages. Human blood monocytes are classified as classical, non-classical and intermediate cells. However, the particular functions of these subsets have been hard to define, with conflicting results and significant overlaps. One likely reason for these ambiguities is in the heterogeneity of these monocyte subsets regrouping cells with divergent functions. To better define monocyte populations, we have analysed expression of 17 markers by multicolour flow cytometry in samples obtained from 28 control donors...
March 10, 2020: Scientific Reports
Karolien Buyl, Makram Merimi, Robim M Rodrigues, Douâa Moussa Agha, Rahma Melki, Tamara Vanhaecke, Dominique Bron, Philippe Lewalle, Nathalie Meuleman, Hassan Fahmi, Vera Rogiers, Laurence Lagneaux, Joery De Kock, Mehdi Najar
Background : As a cell-based therapeutic, AT-MSCs need to create an immuno-reparativeenvironment appropriate for tissue repair. In the presence of injury, MSCs may have to proliferate and face inflammation. Clinical application requires repeated administrations of a high number of cellswith a well-established immune profile. Methods : We have established an immuno-comparative screening by determining the expression of 28 molecules implicated in immune regulation. This screening was performed during cell-expansion and inflammatory priming of AT-MSCs...
March 4, 2020: Journal of Clinical Medicine
Shoji Suzuki, Makoto Ishii, Takanori Asakura, Ho Namkoong, Satoshi Okamori, Kazuma Yagi, Hirofumi Kamata, Tatsuya Kusumoto, Shizuko Kagawa, Ahmed E Hegab, Masaki Yoda, Keisuke Horiuchi, Naoki Hasegawa, Tomoko Betsuyaku
Pulmonary emphysema is a major manifestation of chronic obstructive pulmonary disease and is associated with chronic pulmonary inflammation caused by cigarette smoking, with contributions from immune cells such as neutrophils, macrophages, and lymphocytes. Although matrix metalloproteinases are well-known to contribute to emphysema progression, the role of a disintegrin and metalloproteinase (ADAM) family proteins, other major metalloproteinases, in disease pathogenesis is largely unknown. ADAM17 is a major sheddase that cleaves various cell surface proteins, including CD62L, an adhesion molecule that plays a critical role in promoting the migration of immune cells to the site of inflammation...
March 4, 2020: American Journal of Physiology. Lung Cellular and Molecular Physiology
Christina Begka, Céline Pattaroni, Catherine Mooser, Stéphane Nancey, Kathy D McCoy, Dominique Velin, Michel H Maillard
Expression of Toll-interacting protein (Tollip), a potent TLR modulator, decreases in patients with inflammatory bowel diseases (IBD), whereas Tollip-/- mice are susceptible to colitis. Tollip expression was shown to be reduced in sporadic adenoma . In contrast, we found variable Tollip expression in patients with colitis-associated adenomas. In Tollip-/- mice challenged to develop colitis-associated cancer (CAC), tumor formation was significantly reduced owing to decreased mucosal proliferative and apoptotic indexes...
February 8, 2020: IScience
Wioletta Ratajczak-Wrona, Małgorzata Rusak, Karolina Nowak, Milena Dabrowska, Piotr Radziwon, Ewa Jablonska
Neutrophils (PMN) play a key role in eliciting congenital immune response. These cells are equipped with specific receptors that are located on the surface of their cell membrane. These receptors produce various signals which in turn help in the effective functioning of PMN. The activity of these cells may be modified by factors of endo- and exogenous origin, including xenoestrogens such as bisphenol A (BPA). The aim of this study was to evaluate the effect of BPA on the expression of CD11c, CD14, CD15, CD16, CD62L and CD284 compounds on the surface of neutrophils in women and men...
February 20, 2020: Scientific Reports
O A Peralta, C Carrasco, C Vieytes, M J Tamayo, I Muñoz, S Sepulveda, T Tadich, M Duchens, P Melendez, A Mella, C G Torres
Although, antibiotics are effective in the treatment of bovine mastitis, they do not address the regeneration of mammary glandular tissue and have been associated to the increment in antimicrobial resistance worldwide. Considering the necessity of alternative therapies for this disease of high economic impact and the reported regenerative and antibacterial effects of mesenchymal stem cell (MSCs), we evaluated the safety and efficacy of an allogenic MSC-based intramammary therapy in dairy cows with experimentally induced Staphylococcus aureus clinical mastitis...
February 18, 2020: Scientific Reports
Mohamad El-Zaatari, Shrinivas Bishu, Min Zhang, Helmut Grasberger, Guoqing Hou, Henry R Haley, Brock A Humphries, Li-Jyun Syu, Andrzej Dlugosz, Kathryn E Luker, Gary Luker, Kathryn A Eaton, Nobuhiko Kamada, Marilia Cascalho, John Y Kao
Development of gastric cancer is often preceded by chronic inflammation, but the immune cellular mechanisms underlying this process are unclear. Here we demonstrated that an inflammasome molecule, absent in melanoma 2 (Aim2), was upregulated in gastric cancer patients, and in spasmolytic polypeptide-expressing metaplasia (SPEM) of chronically Helicobacter felis (H. felis)-infected stomachs in mice. However, we found that Aim2 was not necessary for inflammasome function during gastritis. In contrast, Aim2 deficiency led to an increase in gastric CD8+ T cell frequency, which exacerbated metaplasia...
February 13, 2020: JCI Insight
Marina Kleopatra Boziki, Theodoros Karapanayotides, Georgios Papadopoulos, Roza Lagoudaki, Pamela Melo, Christos Bakirtzis, Ioannis Nikolaidis, Evdoxia Gounari, Vasiliki Tsavdaridou, Lemonia Skoura, Theodora Afrantou, Theano Tatsi, Eleni Grigoriadou, Eleni Polyzoidou, Nikolaos Mandoras, Virginia Giantzi, Anna Kalogera-Fountzila, Panagiotis Ioannidis, Dimitrios Parissis, Sygkliti-Henrietta Pelidou, Sofia Zoidou, Nikolaos Grigoriadis
Objectives:  Natalizumab (NTZ), a treatment indicated for patients with highly active Relapsing - Remitting Multiple Sclerosis (RRMS), is known to induce increased relative frequency of lymphocytes. Progressive Multifocal Leukoencephalitis (PML) is a rare but serious adverse event related to NTZ. Moreover, reduced L-selectin (CD62L) expression in T-cells in cryopreserved samples of patients with RRMS under NTZ has been proposed as a biomarker of pre-PML state. We explore the association between L-selectin expression in T-cells and hematological parameters in freshly processed samples of patients with RRMS under NTZ...
February 12, 2020: Neurological Research
John Zaunders, Cynthia Mee Ling Munier, Helen McGuire, Hannah Law, Annett Howe, Yin Xu, Barbara Fazekas de St Groth, Peter Schofield, Daniel Christ, Brad Milner, Solange Obeid, Wayne B Dyer, Nitin K Saksena, Anthony D Kelleher
BACKGROUND: CD4 T-cells that express the chemokine receptor, CCR5, are the most important target of HIV-1 infection, but their functions, phenotypes and anatomical locations are poorly understood. We aimed to use multiparameter flow cytometry to better define the full breadth of these cells. METHODS: High-parameter fluorescence flow and mass cytometry were optimized to analyse subsets of CCR5+ memory CD4 T-cells, including CD25CD127 Tregs, CXCR3+CCR6- Th1, CCR6+CD161+CXCR3- Th17, integrins α4+ß7+ gut-homing, CCR4+ skin-homing, CD62L+ lymph node-homing, CD38+HLA-DR+ activated cells, and CD27-CD28- cytotoxic T lymphocytes (CTL), in a total of 22 samples of peripheral blood, ultrasound-guided fine needle biopsies of lymph nodes and excised tonsils...
February 10, 2020: AIDS
Tobias L Freitag, Joseph R Podojil, Ryan M Pearson, Frank J Fokta, Cecilia Sahl, Marcel Messing, Leif C Andersson, Katarzyna Leskinen, Päivi Saavalainen, Lisa I Hoover, Kelly Huang, Deborah Phippard, Sanaz Maleki, Nicholas J C King, Lonnie D Shea, Stephen D Miller, Seppo K Meri, Daniel R Getts
BACKGROUND & AIMS: Celiac disease could be treated, and potentially cured, by restoring T-cell tolerance to gliadin. We investigated the safety and efficacy of negatively charged, 500 nm, poly(lactide-co-glycolide) nanoparticles encapsulating gliadin protein (TIMP-GLIA) in 3 mouse models of celiac disease. Uptake of these nanoparticles by antigen-presenting cells was shown to induce immune tolerance in other animal models of autoimmune disease. METHODS: We performed studies with C57BL/6, RAG1-/- (C57BL/6), and HLA-DQ8, huCD4 transgenic Ab0 NOD mice...
February 4, 2020: Gastroenterology
Gideon Obasanmi, Noemi Lois, David Armstrong, Nuala-Jane Lavery, Jose Romero Hombrebueno, Aisling Lynch, David M Wright, Mei Chen, Heping Xu
Background/Aims : The aim of this study was to investigate the relationship between alterations in circulating leukocytes and the initiation and progression of DR in people with type 1 diabetes (T1D). Methods : Forty-one patients with T1D [13 mild non-proliferative DR (mNPDR), 14 active proliferative DR (aPDR) and 14 inactive PDR (iPDR)], and 13 age- and gender-matched healthy controls were recruited prospectively. Circulating leukocytes, including CD4+ and CD8+ T-cells, CD14+ CD16- , CD14- CD16+ and CD14+ CD16+ monocytes; CD16+ HLA-DR- neutrophils, CD19+ B-cells and CD56+ natural killer cells and their cell surface adhesion molecules and chemokine receptors (HLA-DR, CD62L, CCR2, CCR5, CD66a, CD157 and CD305) were examined by flow cytometry...
January 30, 2020: Current Eye Research
Christian Secchi, Marco Orecchioni, Marissa Carta, Francesco Galimi, Francesco Turrini, Antonella Pantaleo
Reactive oxygen species (ROS) are central effectors of inflammation and play a key role in cell signaling. Previous reports have described an association between oxidative events and the modulation of innate immunity. However, the role of redox signaling in adaptive immunity is still not well understood. This work is based on a novel investigation of diamide, a specific oxidant of sulfhydryl groups, and it is the first performed in purified T cell tyrosine phosphorylation signaling. Our data show that ex vivo T cells respond to -SH group oxidation with a distinctive tyrosine phosphorylation response and that these events elicit specific cellular responses...
January 14, 2020: Sensors
Bing Zhou, Fuyang Mei, Changhao Wu, Zhifang Liu, Heyun Xu, Yong Cui
CD134 (TNFRSF4) is a member of the TNFR superfamily, which is specifically expressed on T cells. Previous studies have shown that blocking of CD134L-CD134 interaction reduces the percentage of activated T cells and prevents effector T cell-mediated graft rejection in heart transplantation. However, the role of microRNA-regulated inhibition of the CD134 signal in cardiac transplantation of T-regulatory (Treg) cells is not clear. In this study, we found microRNA 744 (miR-744) agomir administration enhanced the expression levels of miR-744 in CD4+ CD25+ Treg cells from heart transplantation mice...
January 9, 2020: Transplantation Proceedings
Michel Paul Johan Teuben, Martijn Hofman, Alba Shehu, Johannes Greven, Zhi Qiao, Kai Oliver Jensen, Frank Hildebrand, Roman Pfeifer, Hans-Christoph Pape
PURPOSE: Dysregulation of polymorphonuclear neutrophil (PMN) biology is associated with the development of inflammatory complications after trauma, such as acute respiratory distress syndrome (ARDS). It has been demonstrated that intramedullary nailing is both associated with altered pulmonary neutrophil deposition and the occurrence of ARDS. This standardized study aimed to characterize the long-term remote neutrophil response in the lungs in case of a femur fracture and intramedullary nailing...
January 3, 2020: International Orthopaedics
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