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CD4 T helper

Amédée Renand, Sarah Habes, Jean-François Mosnier, Hélène Aublé, Jean-Paul Judor, Nicolas Vince, Philippe Hulin, Steven Nedellec, Sylvie Métairie, Isabelle Archambeaud, Sophie Brouard, Jérôme Gournay, Sophie Conchon
Autoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of the liver. This study consists of a comprehensive analysis of immune alterations related to AIH at diagnosis, and during remission phase under treatment. A total of 37 major lymphocyte populations were analyzed from the peripheral blood of new-onset AIH patients (AIHn; n = 14), AIH patients with controlled disease (n = 11), and healthy subjects (n = 14). Liver biopsy analyses were performed to complete the blood phenotypic analysis...
August 2018: Hepatology Communications
Tiehui Wang, Yehfang Hu, Eakapol Wangkahart, Fuguo Liu, Alex Wang, Eman Zahran, Kevin R Maisey, Min Liu, Qiaoqing Xu, Mónica Imarai, Christopher J Secombes
Mammalian interleukin (IL)-2 is a cytokine centrally involved in the differentiation and survival of CD4+ T helper subsets and CD4+ T regulatory cells and in activation of cytotoxic effector lymphocytes. In bony fish, IL2 orthologs have been identified with an additional divergent IL2-Like gene on the same locus present in several fish species. We report here two divergent IL2 paralogs, IL2A and IL2B , in salmonids that originated from the whole genome duplication event in this fish lineage. The salmonid IL2 paralogs differ not only in sequence but also in exon sizes...
2018: Frontiers in Immunology
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
Rafael M Rezende, Amanda J Lanser, Stephen Rubino, Chantal Kuhn, Nathaniel Skillin, Thais G Moreira, Shirong Liu, Galina Gabriely, Bruna A David, Gustavo B Menezes, Howard L Weiner
γδ T cells have many known functions, including the regulation of antibody responses. However, how γδ T cells control humoral immunity remains elusive. Here we show that complete Freund's adjuvant (CFA), but not alum, immunization induces a subpopulation of CXCR5-expressing γδ T cells in the draining lymph nodes. TCRγδ+ CXCR5+ cells present antigens to, and induce CXCR5 on, CD4 T cells by releasing Wnt ligands to initiate the T follicular helper (Tfh) cell program. Accordingly, TCRδ-/- mice have impaired germinal center formation, inefficient Tfh cell differentiation, and reduced serum levels of chicken ovalbumin (OVA)-specific antibodies after CFA/OVA immunization...
August 8, 2018: Nature Communications
Si Chen, Yuting Han, Hao Chen, Jing Wu, Min Zhang
PURPOSE: T helper (Th) 17 cells play a critical role in the development of asthma, but the underlying mechanism of how interleukin (IL)-17 is regulated in allergic airway inflammation is poorly understood. In this study, we investigated the impact of Bcl11b on Th17 response in asthma. METHODS: Blood samples from patients with mild asthma (MA) and severe asthma (SA) were collected. Expression of Bcl11b, IL-4, IL-5, IL-13, IL-17A and transforming growth factor (TGF)-β1 were determined in CD4⁺ T cells and plasma by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA)...
September 2018: Allergy, Asthma & Immunology Research
Yanxia Lu, Hassen Kared, Shu Wen Tan, Etienne Becht, Evan W Newell, Hugo P S Van Bever, Tze Pin Ng, Anis Larbi
Asthma comprises heterogeneous clinical subtypes driven by diverse pathophysiological mechanisms. We characterized the modulation of the inflammatory environment with the phenotype, gene expression, and function of helper CD4 T cells among acutely exacerbated and stable asthma patients. Systemic Th2 immune deviation (IgE and Th2 cytokines) and inflammation (IL-6, CRP) were associated with increased Th17 cells during acute asthma. Th2/Th17 cell differentiation during acute asthma was regulated by the enhanced expression of transcription factors (c-MAF, IRF-4)...
August 7, 2018: Mucosal Immunology
Lan He, Wangpeng Gu, Meng Wang, Xiaoyan Chang, Xiaoyu Sun, Yuan Zhang, Xuan Lin, Chenghua Yan, Weiguo Fan, Pan Su, Yanming Wang, Chunyan Yi, Guomei Lin, Li Li, Yu Jiang, Junxia Lu, Chen Dong, Haikun Wang, Bing Sun
T-follicular helper (TFH ) cells are a subset of CD4+ helper T cells that help germinal center (GC) B-cell differentiation and high-affinity antibody production during germinal center reactions. Whether important extracellular molecules control TFH differentiation is not fully understood. Here, we demonstrate that a secreted protein extracellular matrix protein 1 (ECM1) is critical for TFH differentiation and antibody response. A lack of ECM1 inhibited TFH cell development and impaired GC B-cell reactions and antigen-specific antibody production in an antigen-immunized mouse model...
August 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Wei-Chan Hsu, Ming-Yu Chen, Shu-Ching Hsu, Li-Rung Huang, Cheng-Yuan Kao, Wen-Hui Cheng, Chien-Hsiung Pan, Ming-Sian Wu, Guann-Yi Yu, Ming-Shiu Hung, Chuen-Miin Leu, Tse-Hua Tan, Yu-Wen Su
Activated T cells undergo metabolic reprogramming and effector-cell differentiation but the factors involved are unclear. Utilizing mice lacking DUSP6 (DUSP6-/- ), we show that this phosphatase regulates T cell receptor (TCR) signaling to influence follicular helper T (TFH ) cell differentiation and T cell metabolism. In vitro, DUSP6-/- CD4+ TFH cells produced elevated IL-21. In vivo, TFH cells were increased in DUSP6-/- mice and in transgenic OTII-DUSP6-/- mice at steady state. After immunization, DUSP6-/- and OTII-DUSP6-/- mice generated more TFH cells and produced more antigen-specific IgG2 than controls...
August 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
Kieu-Suong Le, Patricia Amé-Thomas, Karin Tarte, Françoise Gondois-Rey, Samuel Granjeaud, Florence Orlanducci, Etienne D Foucher, Florence Broussais, Reda Bouabdallah, Thierry Fest, Dominique Leroux, Sapna Yadavilli, Patrick A Mayes, Luc Xerri, Daniel Olive
A better characterization of T-cell subsets in the microenvironment of classical Hodgkin lymphoma (cHL) would help to develop immunotherapies. Using multicolor flow cytometry, we identified in 6 of 43 cHL tissue samples a previously unrecognized subset of CD8 T cells coexpressing CXCR5 and inducible T-cell costimulator (ICOS) molecules (CD8CXCR5+ICOS+ ). These cells shared phenotypic features with follicular helper T (TFH ) cells including low CCR7 expression together with high expression of B-cell lymphoma-6, programmed cell death 1, B and T lymphocyte attenuator, CD200, and OX40...
August 14, 2018: Blood Advances
Adam Klocperk, Zuzana Paračková, Markéta Bloomfield, Michal Rataj, Jan Pokorný, Susanne Unger, Klaus Warnatz, Anna Šedivá
DiGeorge syndrome is an immunodeficiency characterized by thymic dysplasia resulting in T cell lymphopenia. Most patients suffer from increased susceptibility to infections and heightened prevalence of autoimmune disorders, such as autoimmune thrombocytopenia. B cells in DiGeorge syndrome show impaired maturation, with low switched-memory B cells and a wide spectrum of antibody deficiencies or dysgammaglobulinemia, presumably due to impaired germinal center responses. We set out to evaluate circulating follicular helper T cells (cTFHs) in DiGeorge syndrome, as markers of T-B interaction in the germinal centers in a cohort of 17 patients with partial DiGeorge and 21 healthy controls of similar age...
2018: Frontiers in Immunology
Joana Vitallé, Iñigo Terrén, Leire Gamboa-Urquijo, Ane Orrantia, Laura Tarancón-Díez, Miguel Genebat, Ezequiel Ruiz-Mateos, Manuel Leal, Susana García-Obregón, Olatz Zenarruzabeitia, Francisco Borrego
The ability of the CD300a inhibitory receptor to modulate immune cell functions and its involvement in the pathogenesis of many diseases has aroused a great interest in this molecule. Within human CD4+ T lymphocytes from healthy donors, the inhibitory receptor CD300a is differentially expressed among different T helper subsets. However, there are no data about the expression and regulation of CD300a receptor on CD4+ T cells from human immunodeficiency virus (HIV)-1-infected patients. The objective of this study was to investigate the expression of CD300a on CD4+ T cells from HIV-infected patients on suppressive combined antiretroviral therapy (cART) and cART naïve patients...
2018: Frontiers in Immunology
Eirini Moysi, Constantinos Petrovas, Richard A Koup
The induction of HIV-1-specific antibodies that can neutralize a broad number of isolates is a major goal of HIV-1 vaccination strategies. However, to date no candidate HIV-1 vaccine has successfully elicited broadly neutralizing antibodies of sufficient quality and breadth for protection. In this review, we focus on the role of follicular helper CD4 T-cells (Tfh) in the development of such cross-reactive protective antibodies. We discuss germinal center (GC) formation and the dynamics of Tfh and GC B cells during HIV-1/SIV infection and vaccination...
August 6, 2018: Retrovirology
Jong Y Lee, Geum J Kim, Jin K Choi, Young-Ae Choi, Na-Hee Jeong, Pil-Hoon Park, Hyukjae Choi, Sang-Hyun Kim
Rheumatoid arthritis (RA) is a progressive autoimmune disease specific to synovial joints; it causes joint damage and other systemic abnormalities, thereby leading to physical disability and early mortality. Marine sponge-derived fungi, Pestalotiopsis sp., secrete immunosuppressive compounds in the culture broth. In the present study, we isolated 4-(hydroxymethyl)catechol (4-HMC) from these fungal species, and evaluated its anti-RA effects using a murine collagen-induced arthritis model and tumor necrosis factor-α-stimulated human RA synovial fibroblasts...
2018: Frontiers in Pharmacology
M Z Luo, T Xu, X H Xue, Y P Wang, P L Wu, X M Chen, X M Tang, X D Zhao, Z Y Zhang
Objective: To investigate the clinical, immunological, and molecular manifestations of nuclear factor kappa-B subunit 2 (NFκB2) gene mutation associated common variable immunodeficiency (CVID) . Methods: A 14-month-old boy diagnosed with NFκB2-mutated CVID was admitted into Children's Hospital of Chongqing Medical University in December 2015. The clinical manifestations, biochemical tests, immunological function, molecular features, treatment, and follow-up of the patient were analyzed. The Chinese and PUBMED databases were searched with the key words "NFκB2" and "immune deficiency" and related literatures were reviewed...
August 2, 2018: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
Tin Sing Lam, Marian van de Meent, Erik W A Marijt, J H Frederik Falkenburg, Inge Jedema
OBJECTIVES: The importance of autologous T-cell responses in immune surveillance against acute myeloid leukemia (AML) remains unclear. Therefore, we investigated the presence and functional reactivity of autoreactive T-cell responses against autologous AML blasts. METHODS: T-cells purified from PB samples harvested from patients during first complete remission were stimulated with autologous AML material harvested at diagnosis. After 12-14 days of co-culture, the T-cells were restimulated with autologous AML cells, and leukemia-reactive T-cell clones were isolated based on their expression of the activation marker CD137...
August 4, 2018: European Journal of Haematology
Nandini Krishnamoorthy, David N Douda, Thayse R Brüggemann, Isabell Ricklefs, Melody G Duvall, Raja-Elie E Abdulnour, Kimberly Martinod, Luciana Tavares, Xiao Wang, Manuela Cernadas, Elliot Israel, David T Mauger, Eugene R Bleecker, Mario Castro, Serpil C Erzurum, Benjamin M Gaston, Nizar N Jarjour, Sally Wenzel, Eleanor Dunican, John V Fahy, Daniel Irimia, Denisa D Wagner, Bruce D Levy
Severe asthma is a debilitating and treatment refractory disease. As many as half of these patients have complex neutrophil-predominant lung inflammation that is distinct from milder asthma with type 2 eosinophilic inflammation. New insights into severe asthma pathogenesis are needed. Concomitant exposure of mice to an aeroallergen and endotoxin during sensitization resulted in complex neutrophilic immune responses to allergen alone during later airway challenge. Unlike allergen alone, sensitization with allergen and endotoxin led to NETosis...
August 3, 2018: Science Immunology
Sang-Heon Park, Jinseol Rhee, Seul-Ki Kim, Jung-Ah Kang, Ji-Sun Kwak, Young-Ok Son, Wan-Su Choi, Sung-Gyoo Park, Jang-Soo Chun
BACKGROUND: We recently demonstrated that BATF, a member of the activator protein-1 (AP-1) family, regulates osteoarthritic cartilage destruction. Here, we explored the roles and regulatory mechanisms of BATF in collagen-induced arthritis (CIA) in mice. METHODS: CIA and K/BxN serum transfer were used to generate inflammatory arthritis models in wild-type (WT) and Batf-/- mice. RA manifestations were determined by examining CIA incidence, clinical score, synovitis, synovial hyperplasia, angiogenesis in inflamed synovium, pannus formation, bone erosion, and cartilage destruction...
August 2, 2018: Arthritis Research & Therapy
Kun Wei, Ben-Chun Jiang, Jing-Hui Guan, Dong-Na Zhang, Meng-Xuan Zhang, Jun-Long Wu, Guang-Ze Zhu
Direct-acting antivirals (DAAs) not only rapidly inhibited hepatitis C virus (HCV) replication but also modulated innate and adaptive immune response in chronic hepatitis C patients. However, the regulatory activity of DAAs to Toll-like receptor 2 (TLR2) stimulation on CD4+ CD25+ CD127dim/- regulatory T cells (Tregs) and T helper (Th) 17 cells was not completely understood. In the present study, a total of 23 patients with chronic HCV genotype 1b infection were enrolled, and blood samples were collected at baseline (treatment naive), end of therapy (EOT), and 12 weeks after EOT (SVR12) with daclatasvir plus asunaprevir therapy...
August 1, 2018: Viral Immunology
Noémie Gensous, Manon Charrier, Dorothée Duluc, Cécile Contin-Bordes, Marie-Elise Truchetet, Estibaliz Lazaro, Pierre Duffau, Patrick Blanco, Christophe Richez
T follicular helper (Tfh) cells are a distinct subset of CD4+ T lymphocytes, specialized in B cell help and in regulation of antibody responses. They are required for the generation of germinal center reactions, where selection of high affinity antibody producing B cells and development of memory B cells occur. Owing to the fundamental role of Tfh cells in adaptive immunity, the stringent control of their production and function is critically important, both for the induction of an optimal humoral response against thymus-dependent antigens but also for the prevention of self-reactivity...
2018: Frontiers in Immunology
Franz-Tassilo Müller-Graff, Brit Fitzner, Robert Jaster, Brigitte Vollmar, Dietmar Zechner
AIM: To evaluate the influence of hyperglycemia on the progression of autoimmune pancreatitis. METHODS: We induced hyperglycemia by repetitive intraperitoneal (ip) injection of 50 mg/kg streptozotocin in MRL/MpJ mice, which develop autoimmune pancreatitis due to a genetic predisposition. We compared the extent of inflammation (histological score, CD3+ lymphocytes, CD8+ T-cells, CD4+ T-cells, Foxp3+ T-helper cells) in the pancreas of hyperglycemic and normoglycemic mice...
July 28, 2018: World Journal of Gastroenterology: WJG
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