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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
Jingjing Zhou, Yiran Wang, Yifei He, Ye Gao, Renhui Wan, Mengxi Cai, Wenwen Li, Rong Chen, Emma Walker, Xiao Zhai, Qijin Wang
Most current studies of type 2 diabetes (T2D) focus on obesity in the pathogenesis of the disease. However, many individuals develop T2D at non-obese body mass index (BMI) level. It is yet unclear whether certain etiological mechanisms discovered in these obese models can apply to non-obese T2D patients. In the present study, we focused on one aspect that was potentially involved in T2D development, the intestinal inflammation, and examined the difference between non-obese T2D patients and BMI-matched healthy controls...
March 15, 2018: Molecular Immunology
Jifu E, Feihu Yan, Zhengchun Kang, Liangliang Zhu, Junjie Xing, Enda Yu
Tumor-draining lymph nodes (TDLNs) are the primary sites of tumor antigen presentation, as well as the origin of metastasis in most cases. Hence, the type and function of immune cells in TDLNs are critical to the microenvironment and potentially affect the clinical outcome of the malignancy. CD8+ CXCR5+ T cells are recently described to present high effector functions in infectious diseases, but their role in colorectal cancer (CRC) remains unclear. In forty-four Stage III CRC patients, we examined the CD8+ CXCR5+ T cells in blood, tumor, and TDLN...
March 12, 2018: Human 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
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
M Cecilia Berin, Alexander Grishin, Madhan Masilamani, Donald Y Leung, Scott H Sicherer, Stacie M Jones, A Wesley Burks, Alice K Henning, Peter Dawson, Joanna Grabowska, Charuta Agashe, Wendy F Davidson, Robert A Wood, Hugh A Sampson
BACKGROUND: Egg allergy is phenotypically heterogeneous. A subset of egg allergic individuals can tolerate egg in an extensively heated form. Inclusion of baked-egg (BE) into their diet accelerates resolution of egg allergy. Conversely, BE reactivity is associated with persistent disease. The immune basis of this clinical heterogeneity is unknown. OBJECTIVES: To study egg-specific antibody, basophil, and T cell responses in children with reactivity or tolerance to BE...
March 5, 2018: Journal of Allergy and Clinical Immunology
Matthew Wiest, Katherine Upchurch, Wenjie Yin, Jerome Ellis, Yaming Xue, Bobby Lanier, Mark Millard, HyeMee Joo, SangKon Oh
Background: T cells play a central role in chronic inflammation in asthma. However, the roles of individual subsets of T cells in the pathology of asthma in patients remain to be better understood. Methods: We investigated the potential signatures of T cell subset phenotypes in asthma using fresh whole blood from adult atopic asthma patients (n = 43) and non-asthmatic control subjects (n = 22). We further assessed their potential clinical implications by correlating asthma severity...
2018: Allergy, Asthma, and Clinical Immunology
Shogo Tanabe, Toshihide Yamashita
During brain development, the immune system mediates neurogenesis, gliogenesis and synapse formation. However, it remains unclear whether peripheral lymphocytes contribute to brain development. Here we identified the subtypes of lymphocytes that are present in neonatal mouse brains and investigated their functions. We found that B-1a cells, a subtype of B cells, were abundant in the neonatal mouse brain and infiltrated into the brain in a CXCL13-CXCR5-dependent manner. B-1a cells promoted the proliferation of oligodendrocyte-precursor cells (OPCs) in vitro, and depletion of B-1a cells from developing brains resulted in a reduction of numbers of OPCs and mature oligodendrocytes...
March 5, 2018: Nature Neuroscience
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
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
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
Carlo Sorrentino, Stefania Livia Ciummo, Giuseppe Cipollone, Sara Caputo, Matteo Bellone, Emma Di Carlo
Prostate cancer (PC) stem-like cells (PCSLCs) are believed to be responsible for PC onset and metastasis. Autocrine and microenvironmental signals dictate PCSLC behavior and patient outcome. In PC patients, interleukin(IL)-30/IL-27p28 has been linked with tumor progression, but the mechanisms underlying this link remain mostly elusive. Here we asked whether IL-30 may favor PC progression by conditioning PCSLCs and assessed the value of blocking IL-30 to suppress tumor growth. IL-30 was produced by PCSLCs in human and murine prostatic intraepithelial neoplasia and displayed significant autocrine and paracrine effects...
February 27, 2018: Cancer Research
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
Lara A Aqrawi, Margarita Ivanchenko, Albin Björk, Jorge I Ramírez Sepúlveda, Juliana Imgenberg-Kreuz, Marika Kvarnström, Philipp Haselmayer, Janicke Liaaen Jensen, Gunnel Nordmark, Karine Chemin, Kathrine Skarstein, Marie Wahren-Herlenius
Genetic investigations of Sjögren's syndrome (SS) have identified a susceptibility locus at p23.3 of chromosome 11, which contains the CXCR5 gene. CXCR5 is a chemokine receptor expressed on B and T cell subsets, and binds the chemotactic ligand CXCL13. We here aimed to link the genetic association with functional effects and explore the CXCR5/CXCL13 axis in SS. Expression quantitative trait loci analysis of the 11q23.3 locus was performed using B cell mRNA expression data from genotyped individuals. Lymphocyte surface markers were assessed by flow cytometry, and CXCL13 levels by a proximity extension assay...
February 17, 2018: Clinical and Experimental Immunology
Marios Koutsakos, Adam K Wheatley, Liyen Loh, E Bridie Clemens, Sneha Sant, Simone Nüssing, Annette Fox, Amy W Chung, Karen L Laurie, Aeron C Hurt, Steve Rockman, Martha Lappas, Thomas Loudovaris, Stuart I Mannering, Glen P Westall, Michael Elliot, Stuart G Tangye, Linda M Wakim, Stephen J Kent, Thi H O Nguyen, Katherine Kedzierska
Immunization with the inactivated influenza vaccine (IIV) remains the most effective strategy to combat seasonal influenza infections. IIV activates B cells and T follicular helper (T FH ) cells and thus engenders antibody-secreting cells and serum antibody titers. However, the cellular events preceding generation of protective immunity in humans are inadequately understood. We undertook an in-depth analysis of B cell and T cell immune responses to IIV in 35 healthy adults. Using recombinant hemagglutinin (rHA) probes to dissect the quantity, phenotype, and isotype of influenza-specific B cells against A/California09-H1N1, A/Switzerland-H3N2, and B/Phuket, we showed that vaccination induced a three-pronged B cell response comprising a transient CXCR5 - CXCR3 + antibody-secreting B cell population, CD21 hi CD27 + memory B cells, and CD21 lo CD27 + B cells...
February 14, 2018: Science Translational Medicine
David Twapokera Mzinza, Henrike Fleige, Kristin Laarmann, Stefanie Willenzon, Jasmin Ristenpart, Julia Spanier, Gerd Sutter, Ulrich Kalinke, Peter Valentin-Weigand, Reinhold Förster
Bronchus-associated lymphoid tissue (BALT) develops at unpredictable locations around lung bronchi following pulmonary inflammation. The formation and composition of BALT have primarily been investigated by immunohistology that, due to the size of the invested organ, is usually restricted to a limited number of histological sections. To assess the entire BALT of the lung, other approaches are urgently needed. Here, we introduce a novel light sheet microscopy-based approach for assessing lymphoid tissue in the lung...
February 12, 2018: Cellular & Molecular Immunology
Ana Cárdeno, Maria K Magnusson, Marianne Quiding-Järbrink, Anna Lundgren
T follicular helper (Tfh)-like cells with potent B-cell helping ability are mobilized into human circulation after parenteral vaccination and are generally held to reflect ongoing germinal center reactions. However, whether mucosal vaccination induces systemic Tfh responses and how such responses may relate to IgA production are unknown. We investigated the frequencies, phenotype and function of circulating Tfh-like CD4+CXCR5+ T cells (cTfh) in adults receiving an oral inactivated enterotoxigenic Escherichia coli vaccine...
February 9, 2018: Scientific Reports
Matthew P Bronnimann, Pamela J Skinner, Elizabeth Connick
The majority of HIV replication occurs in secondary lymphoid organs (SLOs) such as the spleen, lymph nodes, and gut-associated lymphoid tissue. Within SLOs, HIV RNA+ cells are concentrated in the B-cell follicle during chronic untreated infection, and emerging data suggest that they are a major source of replication in treated disease as well. The concentration of HIV RNA+ cells in the B-cell follicle is mediated by several factors. Follicular CD4+ T-cell subsets including T-follicular helper cells and T-follicular regulatory cells are significantly more permissive to HIV than extrafollicular subsets...
2018: Frontiers in Immunology
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