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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
Laura Aragoneses-Fenoll, Gloria Ojeda, María Montes-Casado, Yeny Acosta-Ampudia, Umberto Dianzani, Pilar Portolés, José M Rojo
Class IA phosphatidylinositol 3-kinase (PI3K) catalytic subunits p110α and p110δ are targets in cancer therapy expressed at high levels in T lymphocytes. The role of p110δ PI3K in normal or pathological immune responses is well established, yet the importance of p110α subunits in T cell-dependent immune responses is not clear. To address this problem, mice with p110α conditionally deleted in CD4+ and CD8+ T lymphocytes (p110α-/- ΔT) were used. p110α-/- ΔT mice show normal development of T cell subsets, but slightly reduced numbers of CD4+ T cells in the spleen...
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
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
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
Chien-Chia Chen, Alice Koenig, Carole Saison, Suzan Dahdal, Guillaume Rigault, Thomas Barba, Morgan Taillardet, Dimitri Chartoire, Michel Ovize, Emmanuel Morelon, Thierry Defrance, Olivier Thaunat
Antibody-mediated rejection is currently the leading cause of transplant failure. Prevailing dogma predicts that B cells differentiate into anti-donor-specific antibody (DSA)-producing plasma cells only with the help of CD4+ T cells. Yet, previous studies have shown that dependence on helper T cells decreases when high amounts of protein antigen are recruited to the spleen, two conditions potentially met by organ transplantation. This could explain why a significant proportion of transplant recipients develop DSA despite therapeutic immunosuppression...
2018: Frontiers in Immunology
Devon K Taylor, Nanette Mittereder, Ellen Kuta, Tracy Delaney, Timothy Burwell, Karma Dacosta, Weiguang Zhao, Lily I Cheng, Charles Brown, Anmarie Boutrin, Xiang Guo, Wendy I White, Jie Zhu, Huifang Dong, Michael A Bowen, Jia Lin, Changshou Gao, Li Yu, Madhu Ramaswamy, Marie-Claude Gaudreau, Rob Woods, Ronald Herbst, Gianluca Carlesso
Systemic sclerosis (SSc) is a debilitating inflammatory and fibrotic disease that affects the skin and internal organs. Although the pathophysiology of SSc remains poorly characterized, mononuclear cells, mainly macrophages and T cells, have been implicated in inflammation and fibrosis. Inducible costimulator (ICOS), which is expressed on a subset of memory T helper (TH ) and T follicular helper (TFH ) cells, has been shown to be increased in SSc and associated with disease pathology. However, the identity of the relevant ICOS+ T cells and their contribution to inflammation and fibrosis in SSc are still unknown...
March 7, 2018: Science Translational Medicine
Olivier Désy, Stéphanie Béland, Patrice Vallin, Julie Riopel, Eva Latulippe, Eric Wagner, Sacha A De Serres
Follicular helper T cells (Tfh) are crucial for the production of high-affinity antibodies, such as alloantibodies, by providing the signals for B-cell proliferation and differentiation. Here, we demonstrate that human allogeneic dendritic cells (DC) stimulated with antibodies against HLA class II antigens preferentially differentiate human naive CD4+ T cells into Tfh cells. Following coculture with DCs treated with these antibodies, CD4+ T cells expressed CXCR5, ICOS, IL-21, Bcl-6 and phosphorylated STAT3...
March 5, 2018: Scientific Reports
Megan S F Soon, Ashraful Haque
CD4+ Th cell differentiation is crucial for protecting against blood-stage Plasmodium parasites, the causative agents of malaria. It has been known for decades that more than one type of Th cell develops during this infection, with early models proposing a biphasic Th1/Th2 model of differentiation. Over the past decade, a large body of research, in particular, reports over the past 2-3 y, have revealed substantial complexity in the Th differentiation program during Plasmodium infection. In this article, we review how several studies employing mouse models of malaria, and recent human studies, have redefined the process of Th differentiation, with a particular focus on Th1 and T follicular helper (Tfh) cells...
March 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Mohammad Arif Rahman, Katherine M McKinnon, Tatiana S Karpova, David A Ball, David J Venzon, Wenjin Fan, Guobin Kang, Qingsheng Li, Marjorie Robert-Guroff
Follicular CD8+ T (fCD8) cells reside within B cell follicles and are thought to be immune-privileged sites of HIV/SIV infection. We have observed comparable levels of fCD8 cells between chronically SIV-infected rhesus macaques with low viral loads (LVL) and high viral loads (HVL), raising the question concerning their contribution to viremia control. In this study, we sought to clarify the role of SIV-specific fCD8 cells in lymph nodes during the course of SIV infection in rhesus macaques. We observed that fCD8 cells, T follicular helper (Tfh) cells, and T follicular regulatory cells (Tfreg) were all elevated in chronic SIV infection...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Rajakumar Mandraju, Aakanksha Jain, Yajing Gao, Zhiming Ouyang, Michael V Norgard, Chandrashekhar Pasare
Activation of CD4 T cells by dendritic cells leads to their differentiation into various effector lineages. The nature of the effector lineage is determined by the innate cues provided by dendritic cells to newly primed T cells. Although the cytokines necessary for several effector lineages have been identified, the innate cues that drive Tfh lineage development remain unclear. Here we find that following priming, CD4 T cells undergoing clonal expansion acquire a transient Tfh-like phenotype before differentiating into other effector lineages...
March 5, 2018: Infection and Immunity
Rongxin Wang, Ruiling Xie, Zongchang Song
Chronic hepatitis B virus (HBV) infection is a complex disease with dysregulations in the immune system. Follicular helper T (Tfh) cells are professional B helper cells that are crucial to the development of antibody responses and are involved in a variety of diseases. In this study, we examined the circulating Tfh cells in patients with chronic HBV infection. We observed that CD3+ CD4+ CXCR5+ circulating Tfh cells contained a CD25+ Foxp3+ Treg-like subset that was significantly enriched in patients with chronic HBV infections...
February 28, 2018: Experimental Cell Research
Kyung-Ho Roh, Hannah W Song, Pallab Pradhan, Kevin Bai, Caitlin D Bohannon, Gordon Dale, Jardin Leleux, Joshy Jacob, Krishnendu Roy
B cells play a major role in the adaptive immune response by producing antigen-specific antibodies against pathogens and imparting immunological memory. Following infection or vaccination, antibody-secreting B cells and memory B cells are generated in specialized regions of lymph nodes and spleens, called germinal centers. Here, we report a fully synthetic ex-vivo system that recapitulates the generation of antigen-specific germinal-center (GC) like B cells using material-surface driven polyvalent signaling...
February 21, 2018: Biomaterials
Dirk Baumjohann
T helper (Th) cells are critically involved in adaptive immune responses against various pathogens. In contrast, dysregulated T helper cell responses are associated with a variety of diseases, including autoimmunity, allergies, and cancer. Differentiation of naïve CD4+ T cells into effector T helper cell subsets, including Th1, Th2, Th17, Treg, and Tfh, requires precise dosing of signaling molecules and transcription factors. MicroRNAs (miRNAs), which are small endogenously expressed RNAs that regulate gene expression, play important roles in these processes...
February 27, 2018: Cancer Letters
Defeng Zhang, Yuanbo Wu, Gengyun Sun
The aim of this study was to investigate the role of miR-192 in differentiation of T follicular helper cells in childhood asthma. Blood samples were taken from eighteen children with acute asthma attacks and fifteen healthy children (HC). Quantitative real-time PCR and Western blotting were used to detect the expression levels of miR-192, C-X-C chemokine receptor type 5 (CXCR5), B-cell lymphoma 6 (BCL-6) and inducible T-cell costimulator (ICOS). The flow cytometry was performed to detect the proportion of CD4 + CXCR5+ Tfh cells on CD4 + T lymphocytes...
February 28, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
Li Li, Yan Ma, Yuan Xu, Kamalibaike Maerkeya
Follicular helper T (Tfh) cells are critical regulators of immune responses in several human malignancies. Their characteristics in ovarian cancer (OC) patients remain unclear. In this study, the circulating CD4+ CXCR5+ Tfh cells was examined and compared in OC patients and non-cancer (NC) controls. Data showed that the frequency of PD-1+ Tfh cells was significantly higher in OC patients than in NC controls. Compared to PD-1- Tfh cells, PD-1+ Tfh cells presented higher interleukin (IL)-21 and IL-10 secretion and stronger proliferation...
February 23, 2018: International Immunopharmacology
Jalila Alshekaili, Rochna Chand, Cindy Eunhee Lee, Susan Corley, Kristy Kwong, Ilenia Papa, David A Fulcher, Katrina L Randall, Jennifer W Leiding, Cindy S Ma, Marc R Wilkins, Gulbu Uzel, Chris C Goodnow, Carola G Vinuesa, Stuart G Tangye, Matthew C Cook
A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1hi , but compared to their CD57- PD-1hi counterparts, express little IL-21 or IL-10 among others. Instead, CD57 expression on TFH cells marks cytotoxicity transcriptional signatures that translate into only a weak cytotoxic phenotype. Similarly, circulating PD-1+ CD57+ CD4+ T cells make less cytokine than their CD57- PD-1+ counterparts, but have a prominent cytotoxic phenotype...
February 23, 2018: Scientific Reports
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