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https://www.readbyqxmd.com/read/28637095/selective-cd28-blockade-results-in-superior-inhibition-of-donor-specific-t-follicular-helper-cell-and-antibody-responses-relative-to-ctla-4-ig
#1
I R Badell, G M La Muraglia, D Liu, M E Wagener, G Ding, M L Ford
Donor-specific antibodies (DSA) are a barrier to improved long-term outcomes following kidney transplantation. Costimulation blockade with CTLA-4-Ig has shown promise as a potential therapeutic strategy to control DSA. T follicular helper (Tfh) cells, a subset of CD4(+) T cells required for optimum antibody production, are reliant on the CD28 costimulatory pathway. We have previously shown that selective CD28 blockade leads to superior allograft survival through improved control of CD8(+) T cells relative to CTLA-4-Ig, but the impact of CD28-specific blockade on CD4(+) Tfh cells is unknown...
June 21, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28622456/elevated-ccl25-and-ccr9-expressing-t-helper-cells-in-salivary-glands-of-primary-sj%C3%A3-gren-s-syndrome-patients-potential-new-axis-in-lymphoid-neogenesis
#2
Sofie L M Blokland, Maarten R Hillen, Aike A Kruize, Stephan Meller, Bernhard Homey, Glennda M Smithson, Timothy R D J Radstake, Joel A G van Roon
Introduction T follicular helper (Tfh)-cells play a critical role in germinal center formation and B-cell activation, both hallmarks of primary Sjögren's syndrome (pSS). CCR9-expressing Th-cells have "Tfh-like" characteristics and are increased at mucosa-associated sites in several inflammatory conditions. Because of their unique characteristics and limited evaluation we investigated the local and systemic CCL25/CCR9-axis in pSS. Methods CCL25 protein and mRNA levels and CCR9+ Th-cells were assessed in labial salivary glands (LSG) of pSS and non-Sjögren's sicca (nSS) patients and their correlation with inflammatory and clinical parameters was evaluated...
June 16, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28620390/belatacept-does-not-inhibit-follicular-t-cell-dependent-b-cell-differentiation-in-kidney-transplantation
#3
Gretchen N de Graav, Dennis A Hesselink, Marjolein Dieterich, Rens Kraaijeveld, Wenda Verschoor, Dave L Roelen, Nicolle H R Litjens, Anita S Chong, Willem Weimar, Carla C Baan
Humoral alloreactivity has been recognized as a common cause of kidney transplant dysfunction. B-cell activation, differentiation, and antibody production are dependent on IL-21(+)CXCR5(+)follicular T-helper (Tfh) cells. Here, we studied whether belatacept, an inhibitor of the costimulatory CD28-CD80/86-pathway, interrupts the crosstalk between Tfh- and B-cells more efficiently than the calcineurin inhibitor tacrolimus. The suppressive effects of belatacept and tacrolimus on donor antigen-driven Tfh-B-cell interaction were functionally studied in peripheral blood mononuclear cells from 40 kidney transplant patients randomized to a belatacept- or tacrolimus-based immunosuppressive regimen...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28617936/t-follicular-regulatory-cells-in-mice-and-men
#4
REVIEW
Ana Raquel Maceiras, Valter R Fonseca, Ana Agua-Doce, Luis Graca
It has long been known that CD4 T cells are necessary to provide help to B cells, triggering a germinal center (GC) reaction where affinity maturation and isotype switching occurs. However, the nature of the dedicated CD4 helper T cells, known as T follicular helper (Tfh), was only recently described. Here, we review the biology and function of the recently described T follicular regulatory (Tfr) cells, another CD4 T cell population also found within GCs but with regulatory function and characteristics. Tfr cells have been identified in mice and humans as simultaneously, presenting simultaneously characteristics of T follicular cells (namely CXCR5 expression) and regulatory T cells (including Foxp3 expression)...
June 15, 2017: Immunology
https://www.readbyqxmd.com/read/28604718/the-transcription-factor-runx3-guards-cytotoxic-cd8-effector-t-cells-against-deviation-towards-follicular-helper-t-cell-lineage
#5
Qiang Shan, Zhouhao Zeng, Shaojun Xing, Fengyin Li, Stacey M Hartwig, Jodi A Gullicksrud, Samarchith P Kurup, Natalija Van Braeckel-Budimir, Yao Su, Matthew D Martin, Steven M Varga, Ichiro Taniuchi, John T Harty, Weiqun Peng, Vladimir P Badovinac, Hai-Hui Xue
Activated CD8(+) T cells differentiate into cytotoxic effector (TEFF) cells that eliminate target cells. How TEFF cell identity is established and maintained is not fully understood. We found that Runx3 deficiency limited clonal expansion and impaired upregulation of cytotoxic molecules in TEFF cells. Runx3-deficient CD8(+) TEFF cells aberrantly upregulated genes characteristic of follicular helper T (TFH) cell lineage, including Bcl6, Tcf7 and Cxcr5. Mechanistically, the Runx3-CBFβ transcription factor complex deployed H3K27me3 to Bcl6 and Tcf7 genes to suppress the TFH program...
June 12, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28570278/cxcl13-producing-tfh-cells-link-immune-suppression-and-adaptive-memory-in-human-breast-cancer
#6
Chunyan Gu-Trantien, Edoardo Migliori, Laurence Buisseret, Alexandre de Wind, Sylvain Brohée, Soizic Garaud, Grégory Noël, Vu Luan Dang Chi, Jean-Nicolas Lodewyckx, Céline Naveaux, Hugues Duvillier, Stanislas Goriely, Denis Larsimont, Karen Willard-Gallo
T follicular helper cells (TFH cells) are important regulators of antigen-specific B cell responses. The B cell chemoattractant CXCL13 has recently been linked with TFH cell infiltration and improved survival in human cancer. Although human TFH cells can produce CXCL13, their immune functions are currently unknown. This study presents data from human breast cancer, advocating a role for tumor-infiltrating CXCL13-producing (CXCR5-) TFH cells, here named TFHX13 cells, in promoting local memory B cell differentiation...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28569167/increased-serum-concentrations-of-il-1-beta-il-21-and-th17-cells-in-overweight-patients-with-rheumatoid-arthritis
#7
Hirofumi Shoda, Yasuo Nagafuchi, Yumi Tsuchida, Keiichi Sakurai, Shuji Sumitomo, Keishi Fujio, Kazuhiko Yamamoto
BACKGROUNDS: Obesity is associated with worse disease activity and drug responses in patients with rheumatoid arthritis (RA). However, the immunological mechanisms responsible for the relationship between RA and obesity have not yet been clarified in detail. This study aimed to elucidate the immunological mechanisms contributing to the pathogenesis of RA in overweight patients. METHODS: The frequencies of CD4(+) T cell, B cell and monocyte subsets were analyzed in RA (n = 81) and healthy donors (n = 99) by flow cytometry, and were compared between three groups (body mass index (BMI) <20,  ≥20 to 25, >25)...
May 31, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28564491/abatacept-attenuates-t-follicular-helper-cell-dependent-b-cell-hyperactivity-in-primary-sj%C3%A3-gren-s-syndrome
#8
Gwenny M Verstappen, Petra M Meiners, Odilia B J Corneth, Annie Visser, Suzanne Arends, Wayel H Abdulahad, Rudi W Hendriks, Arjan Vissink, Frans G M Kroese, Hendrika Bootsma
Objective To assess the effect of abatacept (CTLA-4-Ig), which limits T-cell activation, on homeostasis of CD4(+) T-cell subsets and T-cell-dependent B-cell hyperactivity in patients with primary Sjögren's syndrome (pSS). Methods Fifteen pSS patients treated with abatacept were included. Circulating CD4(+) T-cell and B-cell subsets were analyzed by flow cytometry at baseline, on treatment and off treatment. CD4(+) effector T-cell subsets and T regulatory (Treg)-cells were identified based on expression of CD45RA, CXCR3, CCR6, CCR4, CXCR5, programmed death-1 (PD-1), inducible costimulator (ICOS) and FoxP3...
May 31, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28553284/divergent-expression-of-cxcr5-and-ccr5-on-cd4-t-cells-and-the-paradoxical-accumulation-of-t-follicular-helper-cells-during-hiv-infection
#9
REVIEW
John Zaunders, Yin Xu, Stephen J Kent, Kersten K Koelsch, Anthony D Kelleher
Viral infection sets in motion a cascade of immune responses, including both CXCR5(+)CD4(+) T follicular helper (Tfh) cells that regulate humoral immunity and CCR5(+)CD4(+) T cells that mediate cell-mediated immunity. In peripheral blood mononuclear cells, the majority of memory CD4(+) T cells appear to fall into either of these two lineages, CCR5(-)CXCR5(+) or CCR5(+)CXCR5(-). Very high titers of anti-HIV IgG antibodies are a hallmark of infection, strongly suggesting that there is significant HIV-specific CD4(+) T cell help to HIV-specific B cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28551095/an-in-depth-analysis-identifies-two-new-independent-signals-in-11q23-3-associated-with-vitiligo-in-the-chinese-han-population
#10
Suli Zhao, Fang Fang, Xianfa Tang, Jinfa Dou, Wenjun Wang, Xiaodong Zheng, Liangdan Sun, Anping Zhang
BACKGROUND: Vitiligo is an autoimmune disease, characterized by progressive loss of skin pigmentation, which is caused by the interactions of multiple factors, such as heredity, immunity and environment. Recently, a single nucleotide polymorphism (SNP) rs638893 at 11q23.3 region was identified as a risk factor for vitiligo in genome-wide association studies and multiple SNPs in this region have been associated with other autoimmune diseases. OBJECTIVE: This study aims to identify additional susceptibility variants associated with vitiligo at 11q23...
May 3, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28516880/abatacept-therapy-reduces-cd28-cxcr5-follicular-helper-like-t-cells-in-patients-with-rheumatoid-arthritis
#11
Shunsuke Fukuyo, Shingo Nakayamada, Shigeru Iwata, Satoshi Kubo, Kazuyoshi Saito, Yoshiya Tanaka
OBJECTIVES: The characteristics of T cells targeted by abatacept (ABT) in cases of rheumatoid arthritis (RA) are still unknown. The goal of the study was to determine the pathogenicity of T cells and the predictors of therapeutic effects of ABT. METHODS: We analysed the peripheral T cell phenotype of 34 RA patients via flow cytometry. The correlation of the phenotypes of CD4+ T cells with clinical disease activity and change in CD4+ T cell subsets at baseline and 24 weeks after ABT treatment were evaluated...
April 27, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28503175/heterogeneity-of-phenotype-and-function-reflects-the-multistage-development-of-t-follicular-helper-cells
#12
Marta Trüb, Tom A Barr, Vicky L Morrison, Sheila Brown, Stefano Caserta, Jordan Rixon, Alasdair Ivens, David Gray
T follicular helper cells (Tfh) provide crucial signals for germinal center (GC) formation, but Tfh populations are heterogeneous. While PD1(hi) Tfh are important in the GC response, the function of the PD1(lo) Tfh-like subset is unknown. We show that these cells, like the PD1(hi) GC-Tfh, depend upon B cells; however, their entry to follicles is independent of CXCR5 or cognate interactions with B cells. The differentiation into PD1(hi) Tfh is dependent on MHC class II interactions with B cells and requires CXCR5...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28500636/immune-correlates-of-hepatitis-b-surface-antigen-spontaneous-seroconversion-in-hepatitis-b-e-antigen-negative-chronic-hepatitis-b-patients
#13
Ashish Kumar Vyas, Barjesh Chander Sharma, Shiv Kumar Sarin, Nirupma Trehanpati
BACKGROUND: Hepatitis B surface antigen (HBsAg) seroconversion in HBeAg-ve chronic hepatitis B (CHB) infection is rare, possibly due to poor antigen processing and impaired humoral response. We investigated the role of dendritic cells (DCs), T follicular helper (TFH) cells and plasma B cells in seroconversion. METHODS: HBeAg-ve (n=135) CHB patients with raised ALT at baseline were followed-up. Patients undergoing HBsAg sero-conversion (Gr. I, n=11) were compared with non-converters with low (Gr...
May 13, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28485792/increased-expression-of-cxcr5-and-cxcl13-in-mice-with-experimental-autoimmune-myocarditis
#14
F-L Han, F Liang, T-C Jiang, M Liu
OBJECTIVE: Myocarditis is an inflammatory heart muscle disease associated with cardiac dysfunction, and autoimmunity is considered to play an important role in the pathogenesis of myocarditis. CXCL13 and its receptor CXCR5 have been reported to be associated with many diseases including some cancers and inflammatory diseases, but so far there has been no report on CXCR5/CXCL13 expression in myocarditis. MATERIALS AND METHODS: With a mouse experimental autoimmune myocarditis (EAM) model, it was found that the mRNA and protein expression of both CXCR5 and CXCL13 were increased in myocardial tissue in the EAM mice...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28482188/pregnancy-favors-the-expansion-of-circulating-functional-follicular-helper-t-cells
#15
Clarice Monteiro, Taissa M Kasahara, José Roberto Castro, Priscila M Sacramento, Joana Hygino, Newton Centurião, Tatiane Cassano, Lana M Ferreira Lopes, Simone Leite, Vander Guimarães Silva, Sudhir Gupta, Cleonice A M Bento
Pregnancy favors antibody production, and some evidence has suggested a direct effect of estrogen on B cells. The impact of pregnancy on circulating follicular helper T (TFH) cells, typically identified by the expression of CD45RO and CXCR5, has not been previously investigated. Here, the percentage of TFH cells, co-expressing or not PD-1, ICOS, or CXCR3 markers was significantly higher in pregnant women (PW) as compared with non-pregnant ones (nPW). Furthermore, the percentage of CXCR3(+) TFH cells able to produce IL-6, IL-21, and IL-10 was significantly higher in PW than nPW...
April 27, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28480794/dimethyl-fumarate-induces-changes-in-b-and-t-lymphocyte-function-independent-of-the-effects-on-absolute-lymphocyte-count
#16
Erin E Longbrake, Claudia Cantoni, Salim Chahin, Francesca Cignarella, Anne H Cross, Laura Piccio
BACKGROUND: Dimethyl fumarate (DMF) is used to treat relapsing multiple sclerosis and causes lymphopenia in a subpopulation of treated individuals. Much remains to be learned about how the drug affects B- and T-lymphocytes. OBJECTIVES: To characterize changes in B- and T-cell phenotype and function induced by DMF and to investigate whether low absolute lymphocyte count (ALC) is associated with unique functional changes. METHODS: Peripheral blood mononuclear cells (PBMCs) were collected from DMF-treated patients, untreated patients, and healthy controls...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28468877/preservation-of-peripheral-t-follicular-helper-cell-function-in-hiv-controllers
#17
Supranee Buranapraditkun, Franco Pissani, Jeffrey E Teigler, Bruce T Schultz, Galit Alter, Mary Marovich, Merlin L Robb, Michael A Eller, Jeff Martin, Steven Deeks, Nelson L Michael, Hendrik Streeck
The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28463977/production-of-igg-antibodies-to-pneumococcal-polysaccharides-is-associated-with-expansion-of-icos-circulating-memory-t-follicular-helper-cells-which-is-impaired-by-hiv-infection
#18
Laila N Abudulai, Sonia Fernandez, Karli Corscadden, Sally A Burrows, Michael Hunter, M Christian Tjiam, Lea-Ann S Kirkham, Jeffrey J Post, Martyn A French
Dysfunction of T follicular-helper (TFH) cells is a possible cause of impaired germinal centre (GC) and IgG antibody responses in individuals with human immunodeficiency virus-1 (HIV-1) infection and might contribute to decreased magnitude and isotype diversification of IgG antibodies to pneumococcal polysaccharides (PcPs). We examined the production of IgG1 and IgG2 antibodies to PcPs 4, 6B, 9V and 14 by enumerating antibody secreting cells (ASCs) at day (D) 7 and determining fold-increase in serum antibody levels at D28 after vaccination with unconjugated PcPs in HIV seronegative subjects (n = 20) and in HIV patients who were receiving antiretroviral therapy (ART) (n = 28) or who were ART-naive (n = 11) and determined their association with ICOS+ and ICOS- circulating memory TFH (cmTFH) cells (CD4+CD45RA-CD27+CXCR5+PD-1+) and short lived plasmablasts (SPBs) at D7, and with PcP-specific and total IgM+ and IgG+ memory B cells at D0...
2017: PloS One
https://www.readbyqxmd.com/read/28454789/cxcr5-overexpressing-mesenchymal-stromal-cells-exhibit-enhanced-homing-and-can-decrease-contact-hypersensitivity
#19
Xiaoran Zhang, Weijun Huang, Xiaoyong Chen, Yufan Lian, Jiancheng Wang, Chuang Cai, Li Huang, Tao Wang, Jie Ren, Andy Peng Xiang
Mesenchymal stromal cells (MSCs) can modulate inflammation and contribute to tissue regeneration and, thus, have emerged as a promising option for cell-based therapy. However, the ability of MSCs to migrate to injured tissues still needs to be improved. In this study, we investigated whether genetically engineered MSCs could exhibit increased migratory properties and improved therapeutic efficacy. Using a mouse model of contact hypersensitivity (CHS), chemokine gene expression screening revealed that CXCL13 changed most significantly in injured tissue...
June 7, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28445512/proportions-of-circulating-follicular-helper-t-cells-are-reduced-and-correlate-with-memory-b-cells-in-hiv-infected-children
#20
Daniel M Muema, Gladys N Macharia, Babatunde A Olusola, Amin S Hassan, Greg W Fegan, James A Berkley, Britta C Urban, Eunice W Nduati
INTRODUCTION: HIV causes defects in memory B cells in children, but the mechanisms of those defects have not been fully elucidated. One possible mechanism is the lack of T-cell help to B cells during immune reactions. However, few studies have assessed the effect of HIV on follicular helper T cells (TFH cells) in children. METHODS: In this study, follicular-homing CD4 T cells and memory B cells were assessed in HIV-infected children and compared with children from the community...
2017: PloS One
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