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Follicular T helper

Abdullah Aljurayyan, Suttida Puksuriwong, Muhammad Ahmed, Ravi Sharma, Madhan Krishnan, Salil Sood, Katherine Davies, Devika Rajashekar, Sam Leong, Paul S McNamara, Stephen Gordon, Qibo Zhang
There is increasing interest recently in developing intranasal vaccines against respiratory tract infections. Antibody response is critical in vaccine-induced protection and TFH is considered important in mediating antibody response. Most data supporting the role for TFH in antibody response are from animal studies, and direct evidence from humans is limited, apart from TFH -like cells in blood. We studied activation and induction of TFH and its role on anti-influenza antibody response by live-attenuated influenza vaccine(LAIV) in human nasopharynx-associated lymphoid tissue(NALT)...
March 21, 2018: Journal of Virology
Seung-Chul Choi, Zhiwei Xu, Wei Li, Hong Yang, Derry C Roopenian, Herbert C Morse, Laurence Morel
Mouse models of lupus have shown that multiple immune cell types contribute to autoimmune disease. This study sought to investigate the involvement of B cells and dendritic cells in supporting the expansion of inflammatory and regulatory CD4+ T cells that are critical for lupus pathogenesis. We used lupus-prone B6.NZM2410.Sle1.Sle2.Sle3 (TC) and congenic C57BL/6J (B6) control mice to investigate how the genetic predisposition of these two cell types controls the activity of normal B6 T cells. Using an allogeneic in vitro assay, we showed that TC B1-a and conventional B cells expanded Th17 cells significantly more than their B6 counterparts...
March 21, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Cynthia Louis, Chris Burns, Ian Wicks
The pathogenesis of autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) is driven by genetic predisposition and environmental triggers that lead to dysregulated immune responses. These include the generation of pathogenic autoantibodies and aberrant production of inflammatory cytokines. Current therapies for RA and other autoimmune diseases reduce inflammation by targeting inflammatory mediators, most of which are innate response cytokines, resulting in generalized immunosuppression...
2018: Frontiers in Immunology
Susan Malkiel, Ashley N Barlev, Yemil Atisha-Fregoso, Jolien Suurmond, Betty Diamond
Plasma cells (PCs) are responsible for the production of protective antibodies against infectious agents but they also produce pathogenic antibodies in autoimmune diseases, such as systemic lupus erythematosus (SLE). Traditionally, high affinity IgG autoantibodies are thought to arise through germinal center (GC) responses. However, class switching and somatic hypermutation can occur in extrafollicular (EF) locations, and this pathway has also been implicated in SLE. The pathway from which PCs originate may determine several characteristics, such as PC lifespan and sensitivity to therapeutics...
2018: Frontiers in Immunology
Matteo Ugolini, Jenny Gerhard, Sanne Burkert, Kristoffer Jarlov Jensen, Philipp Georg, Friederike Ebner, Sarah M Volkers, Shruthi Thada, Kristina Dietert, Laura Bauer, Alexander Schäfer, Elisa T Helbig, Bastian Opitz, Florian Kurth, Saubashya Sur, Nickel Dittrich, Sumanlatha Gaddam, Melanie L Conrad, Christine S Benn, Ulrike Blohm, Achim D Gruber, Andreas Hutloff, Susanne Hartmann, Mark V Boekschoten, Michael Müller, Gregers Jungersen, Ralf R Schumann, Norbert Suttorp, Leif E Sander
Live attenuated vaccines are generally highly efficacious and often superior to inactivated vaccines, yet the underlying mechanisms of this remain largely unclear. Here we identify recognition of microbial viability as a potent stimulus for follicular helper T cell (TFH cell) differentiation and vaccine responses. Antigen-presenting cells (APCs) distinguished viable bacteria from dead bacteria through Toll-like receptor 8 (TLR8)-dependent detection of bacterial RNA. In contrast to dead bacteria and other TLR ligands, live bacteria, bacterial RNA and synthetic TLR8 agonists induced a specific cytokine profile in human and porcine APCs, thereby promoting TFH cell differentiation...
March 19, 2018: Nature Immunology
S N Yang, X Pu, S L Xiang, J P Chen, L Pei
Objective: To investigate the effect of brain derived neurotrophic factor (BDNF) on mesenchymal stem cells (MSC) inhibiting follicular helper T cells (Tfh cells). Methods: The contents of indoleamine 2,3-dioxygenase (IDO), IL-10, TGF-β and IL-21 in MSC culture supernatant were detected by ELISA; The peripheral blood of healthy volunteers were collected, and lymphocyte in peripheral blood was separated by human lymphocyte separation solution; Co-cultures of MSC and lymphocyte were performed by Transwell chamber, and the proportion of CD4(+)CXCR5(+) Tfh cells and their subtypes were detected by flow cytometry...
January 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Gaetan Barbet, Leif E Sander, Matthew Geswell, Irina Leonardi, Andrea Cerutti, Iliyan Iliev, J Magarian Blander
Live vaccines historically afford superior protection, yet the cellular and molecular mechanisms mediating protective immunity remain unclear. Here we found that vaccination of mice with live, but not dead, Gram-negative bacteria heightened follicular T helper cell (Tfh) differentiation, germinal center formation, and protective antibody production through the signaling adaptor TRIF. Complementing the dead vaccine with an innate signature of bacterial viability, bacterial RNA, recapitulated these responses...
March 9, 2018: Immunity
Mitsuhiro Akiyama, Tsutomu Takeuchi
IgG4-related disease is a heterogeneous immune-mediated fibroinflammatory condition that can affect every single organ. This disease is more prevalent in the elderly (the mean age of patients is above 60 years) and the prevalence rate is estimated to be over 4.6 per 100,000 population. Before making a diagnosis, the exclusion of malignancies, lymphoma, anti-neutrophil cytoplasmic antibody-associated vasculitis, multicentric Castleman disease, and other mimickers is crucial for appropriate treatment. Broad management guidelines have been published emphasizing the need for prompt treatment and the use of glucocorticoids as first-line drug therapy for induction of remission...
March 15, 2018: Drugs & Aging
Dalia E Gaddis, Lindsey E Padgett, Runpei Wu, Chantel McSkimming, Veronica Romines, Angela M Taylor, Coleen A McNamara, Mitchell Kronenberg, Shane Crotty, Michael J Thomas, Mary G Sorci-Thomas, Catherine C Hedrick
Regulatory T (Treg) cells contribute to the anti-inflammatory response during atherogenesis. Here we show that during atherogenesis Treg cells lose Foxp3 expression and their immunosuppressive function, leading to the conversion of a fraction of these cells into T follicular helper (Tfh) cells. We show that Tfh cells are pro-atherogenic and that their depletion reduces atherosclerosis. Mechanistically, the conversion of Treg cells to Tfh cells correlates with reduced expression of IL-2Rα and pSTAT5 levels and increased expression of IL-6Rα...
March 15, 2018: Nature Communications
David Vallois, Aurélie Dupuy, Francois Lemonnier, George Allen, Edoardo Missiaglia, Virginie Fataccioli, Nicolas Ortonne, Aline Clavert, Richard Delarue, Marie-Christine Rousselet, Bettina Fabiani, Francisco Llamas-Gutierrez, Seishi Ogawa, Margot Thome, Young Hyeh Ko, Keisuke Kataoka, Philippe Gaulard, Laurence de Leval
No abstract text is available yet for this article.
March 15, 2018: Haematologica
Xiaowen Wang, Qingyang Dong, Qian Li, Yuanyuan Li, Dianyuan Zhao, Jinjie Sun, Junliang Fu, Fanping Meng, Hu Lin, Junjie Luan, Biao Liu, Min Wang, Fusheng Wang, Fuchu He, Li Tang
BACKGROUND & AIMS: Production of neutralizing antibodies against hepatitis B surface antigen (HBsAg) is dysregulated in patients with persistent hepatitis V virus (HBV) infection. We investigated mechanisms by which this immune response to the virus is disrupted and whether it can be restored to promote clearance of HBV. METHODS: Immune-competent C57BL/6N and C57BL/6J, as well as mice deficient in follicular helper T cells (Tfh cell-deficient), B cells, or Foxp3+ T-regulatory cells (Treg cell-deficient), were given hydrodynamic injections of pAAV/HBV1...
March 12, 2018: Gastroenterology
Maria Vono, Christiane Sigrid Eberhardt, Elodie Mohr, Floriane Auderset, Dennis Christensen, Mirco Schmolke, Rhea Coler, Andreas Meinke, Peter Andersen, Paul-Henri Lambert, Beatris Mastelic-Gavillet, Claire-Anne Siegrist
Neonates and infants are more vulnerable to infections and show reduced responses to vaccination. Consequently, repeated immunizations are required to induce protection and early life vaccines against major pathogens such as influenza are yet unavailable. Formulating antigens with potent adjuvants, including immunostimulators and delivery systems, is a demonstrated approach to enhance vaccine efficacy. Yet, adjuvants effective in adults may not meet the specific requirements for activating the early life immune system...
2018: Frontiers in Immunology
James L Quinn, Gaurav Kumar, Agnieshka Agasing, Rose M Ko, Robert C Axtell
Both T cells and B cells are implicated in the pathology of multiple sclerosis (MS), but how these cells cooperate to drive disease remains unclear. Recent studies using experimental autoimmune encephalomyelitis (EAE) demonstrated that the TH17 pathway is correlated with increased numbers of ectopic B-cell follicles in the central nervous system (CNS). As follicular T helper (TFH) cells are regulators of B cell responses, we sought to examine the role of TFH cells in EAE induced by the transfer of myelin-specific TH17 cells (TH17-EAE)...
2018: Frontiers in Immunology
Monica Vaccari, Genoveffa Franchini
Germinal centers (GCs) are organized lymphoid tissue microstructures where B cells proliferate and differentiate into memory B cells and plasma cells. A few distinctive subsets of highly specialized T cells gain access to the GCs by expressing the B cell zone-homing C-X-C chemokine receptor type 5 (CXCR5) while losing the T cell zone-homing chemokine receptor CCR7. Help from T cells is critical to induce B cell proliferation and somatic hyper mutation and to limit GC reactions. CD4+ T follicular helper (TFH ) cells required for the formation of GCs and for the generation of long-lived, high-affinity B cells...
2018: Frontiers in Immunology
Valter R Fonseca, Vasco C Romão, Ana Agua-Doce, João Eurico Fonseca, Luis Graca
We are excited to find that most of our conclusions (1) were replicated in an independent larger primary Sjögren's syndrome (pSS) cohort, as reported by Verstappen et al in their Letter (Verstappen G et al, Arthritis & Rheumatology, in press). Indeed, our colleagues were also able to demonstrate that the ratio of blood T follicular regulatory (Tfr) / T follicular helper (Tfh) cells were increased in pSS patients, and specifically within pSS patients with focus score (FS) ≥ 1, supporting its discriminative value for the diagnosis of pSS...
March 13, 2018: Arthritis & Rheumatology
Peter T Sage, Frank A Schildberg, Raymond A Sobel, Vijay K Kuchroo, Gordon J Freeman, Arlene H Sharpe
The programmed death (PD)-1 coinhibitory receptor regulates the balance between T cell activation and tolerance. Although the PD-1 ligands, PD-L1 and PD-L2, are expressed on a variety of cell types, the cell type-specific functions of PD-1 ligands in inducing signals through PD-1 are unknown. In this study, we use PD-L1 conditional knockout mice to investigate the cell type-specific functions of PD-L1. We demonstrate that PD-L1 expressed on dendritic cells (DCs), and to a lesser extent on B cells, attenuates the progression of experimental autoimmune encephalomyelitis and inhibits naive and effector T cells...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Yongxia Wu, Steven Schutt, Katelyn Paz, Mengmeng Zhang, Ryan P Flynn, David Bastian, M Hanief Sofi, Hung Nguyen, Min Dai, Chen Liu, Ying-Jun Chang, Bruce R Blazar, Xue-Zhong Yu
Chronic graft-versus-host disease (cGVHD) is characterized as autoimmune-like fibrosis and antibody production mediated by pathogenic T-cells and B-cells. MicroRNA (miR)-17-92 influences the survival, differentiation and function of lymphocytes in cancer, infections and autoimmunity. To determine whether miR-17-92 regulates T- and B-cell responses in cGVHD, we generated mice conditionally deficient for miR-17-92 in T-cells, B-cells, or both. Using murine models of allogeneic bone marrow transplantation (allo-BMT), we demonstrate that expression of miR-17-92 in donor T- and B-cells is essential for the induction of both scleroderma and bronchiolitis obliterans in cGVHD...
March 12, 2018: Blood
Liannv Qiu, Yonglie Zhou, Qinhua Yu, Sujie Zheng, Zhenni Wang, Qiang Huang
Chronic lymphocytic leukaemia (CLL) is characterized by an abnormal expansion of mature B cells with variable progression. Follicular T helper (Tfh) cells help B cells differentiate into plasma cells or long-lived memory B cells in germinal centres (GCs). However, the role of Tfh cells in CLL is poorly understand, and whether it plays a critical role in disease progression in vivo is lacking. In this study, we investigate the dynamic change of circulating Tfh cells in peripheral blood from patients with CLL during the treatment periods to evaluate their utility to predict disease progression...
March 8, 2018: Immunology Letters
Mark L Lang
Vaccination with CD1d-binding glycolipid adjuvants and co-administered protein, lipid, and carbohydrate antigens leads to invariant natural killer T (NKT) cell-dependent enhancement of protective B cell responses. NKT cell activation boosts the establishment of protein antigen-specific B cell memory and long-lived plasma cell (LLPC) compartments. NKT cells may exert a similar effect on some carbohydrate-specific B cells, but not lipid-specific B cells. The mechanisms of action of NKT cells on B cell responsiveness and subsequent differentiation into memory B cells and LLPC is dependent on CD1d expression by dendritic cells and B cells that can co-present glycolipids on CD1d and antigen-derived peptide on MHCII...
2018: Frontiers in Immunology
Fang Gong, Hua-Yan Zhu, Jie Zhu, Qiao-Jing Dong, Xuan Huang, Dong-Jin Jiang
The pathogenesis of allergic asthma is primarily characterized by abnormality in immunoglobin(Ig)E pathway, suggesting a possible role for follicular helper T cells (Tfh) in the genesis of excessive IgE accumulation. The blood chemokine (C-X-C motif) receptor 5 (CXCR)5+ CD4+ T cells, known as "circulating" Tfh, share common functional characteristics with Tfh cells from germinal centers. The aim of this study was to determine the phenotypes and functions of circulating CXCR5+ CD4+ T cells in allergic asthmatics...
March 5, 2018: Immunology Letters
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