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Follicular helper T cells

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https://www.readbyqxmd.com/read/29791846/myosin-iia-promotes-antibody-responses-by-regulating-b-cell-activation-acquisition-of-antigen-and-proliferation
#1
Robbert Hoogeboom, Elizabeth M Natkanski, Carla R Nowosad, Dessislava Malinova, Rajesh P Menon, Antonio Casal, Pavel Tolar
B cell responses are regulated by antigen acquisition, processing, and presentation to helper T cells. These functions are thought to depend on contractile activity of non-muscle myosin IIa. Here, we show that B cell-specific deletion of the myosin IIa heavy chain reduced the numbers of bone marrow B cell precursors and splenic marginal zone, peritoneal B1b, and germinal center B cells. In addition, myosin IIa-deficient follicular B cells acquired an activated phenotype and were less efficient in chemokinesis and extraction of membrane-presented antigens...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29786112/ctla%C3%A2-4-interferes-with-the-hbv%C3%A2-specific-t-cell-immune-response-review
#2
Hui Cao, Ruiwen Zhang, Wei Zhang
Hepatitis B virus (HBV) infection is a major cause of hepatic inflammation. Successful HBV clearance in patients is associated with sustained viral control by effector T cells. Compared with acute hepatitis B, chronic HBV infection is associated with the depletion of T cells, resulting in weak or absent virus‑specific T cells reactivity, which is described as 'exhaustion'. This exhaustion is characterized by impaired cytokine production and sustained expression of multiple coinhibitory molecules. Cytotoxic T lymphocyte‑associated antigen‑4 (CTLA‑4) is one of many coinhibitory molecules that can attenuate T cell activation by inhibiting costimulation and transmitting inhibitory signals to T cells...
May 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29784613/cryoglobulinemic-glomerulonephritis-associated-with-nodal-and-renal-infiltration-by-t-cell-lymphoma-of-t-follicular-helper-phenotype-a-case-report
#3
Jennifer Li, Marille Umakanathan, Chow Heok P'ng, Winny Varikatt, Fiona Kwok, Ming-Wei Lin, Mirna Vucak-Dzumhur
We present a unique case of cryoglobulinemic glomerulonephritis associated with nodal and renal infiltration by T-cell lymphoma of T-follicular helper phenotype. The patient presented with transient neurologic symptoms, severe nephritic syndrome with nephrotic-range proteinuria, and acute kidney injury. He had elevated double-stranded DNA levels, low complement levels, detectable cryoglobulin, and detectable immunoglobulin M (IgM) paraprotein. The kidney biopsy showed cryoglobulinemic glomerulonephritis with a membranoproliferative pattern and diffuse interstitial infiltrates on light microscopy; IgM, C3 but weak IgG, C1q, and negative C4d staining on immunofluorescence; and deposits with organized substructures on electron microscopy...
May 18, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29781814/lymphoid-tissue-fibrosis-is-associated-with-impaired-vaccine-responses
#4
Cissy Kityo, Krystelle Nganou Makamdop, Meghan Rothenberger, Jeffrey G Chipman, Torfi Hoskuldsson, Gregory J Beilman, Bartosz Grzywacz, Peter Mugyenyi, Francis Ssali, Rama S Akondy, Jodi Anderson, Thomas E Schmidt, Thomas Reimann, Samuel P Callisto, Jordan Schoephoerster, Jared Schuster, Proscovia Muloma, Patrick Ssengendo, Eirini Moysi, Constantinos Petrovas, Ray Lanciotti, Lin Zhang, Maria T Arévalo, Benigno Rodriguez, Ted M Ross, Lydie Trautmann, Rafick-Pierre Sekaly, Michael M Lederman, Richard A Koup, Rafi Ahmed, Cavan Reilly, Daniel C Douek, Timothy W Schacker
Vaccine responses vary by geographic location. We have previously described how HIV-associated inflammation leads to fibrosis of secondary lymph nodes (LNs) and T cell depletion. We hypothesized that other infections may cause LN inflammation and fibrosis, in a process similar to that seen in HIV infection, which may lead to T cell depletion and affect vaccine responses. We studied LNs of individuals from Kampala, Uganda, before and after yellow fever vaccination (YFV) and found fibrosis in LNs that was similar to that seen in HIV infection...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781755/more-robust-gut-immune-responses-induced-by-combining-intranasal-and-sublingual-routes-for-prime-boost-immunization
#5
Hye Suk Hwang, Sao Puth, Wenzhi Tan, Vivek Verma, Kwangjoon Jeong, Shee Eun Lee, Joon Haeng Rhee
Norovirus causes acute and debilitating gastroenteritis, characterized by vomiting and diarrhea. We recently reported a recombinant GII. 4 P domain particle (Pd) vaccine adjuvanted with a flagellin, Vibrio vulnificus FlaB, effectively promoting both humoral and cell-mediated immune responses. In the previous study, we found that sublingual (SL) immunization induced higher fecal secretory IgA (SIgA) responses while intranasal (IN) route provided higher amplitude of humoral and cellular immune responses in the systemic compartment...
May 21, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29781221/aberrant-expansion-and-function-of-t-follicular-helper-cell-subsets-in-igg4-related-disease
#6
Yu Chen, Wei Lin, Hongxian Yang, Mu Wang, Panpan Zhang, Ruie Feng, Hua Chen, Linyi Peng, Xuan Zhang, Yan Zhao, Xiaofeng Zeng, Fengchun Zhang, Wen Zhang, Peter E Lipsky
OBJECTIVE: To determine the number and function of Tfh cell subsets in IgG4-RD. METHODS: Mononuclear cells from peripheral blood and involved tissues of IgG4-RD patients were collected. Tfh cell subsets, mRNA levels of Bcl-6, Blimp-1 and IL-21 were tested. Immunohistochemistry and immunofluorescence techniques were used to assess the location of IL-21, Bcl-6, and (CD4+CXCR5+) Tfh cells in the involved tissues. Furthermore, by in vitro cell co-culture, the abilities of cTfh cell subsets to induce B cells proliferation, apoptosis, differentiation, and production of IgG4 were explored...
May 21, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29774664/the-lupus-associated-fc%C3%AE-riib-i232t-polymorphism-results-in-impairment-in-the-negative-selection-of-low-affinity-germinal-center-b-cells-via-c-abl
#7
Jyun-Pei Jhou, I-Shing Yu, Haw Hwai, Chih-Shan Chen, Pei-Lung Chen, Shiang-Jong Tzeng
OBJECTIVE: FcγRIIB is an essential negative regulator of B cells to block BCR signaling and to trigger c-Abl-dependent apoptosis of B cells. FcγRIIB-deficient mice display splenomegaly with expansion of B cells, leading to lupus. FcγRIIB-I232T is a hypo-functional polymorphism associated with lupus susceptibility in humans, an autoimmune disease linked to diminished deletion of autoreactive B cells. In the context of FcγRIIB-I232T polymorphism, we investigated the role of FcγRIIB in the deletion of low-affinity germinal center (GC) B cells, an important mechanism for preventing autoimmunity...
May 17, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29773681/decreased-expression-of-circulating-aire-and-increased-tfh-tfr-cells-in-myasthenia-gravis-patients
#8
Sijia Zhao, Jiaqi Ding, Shengyuan Wang, Chuan Li, Peng Guo, Min Zhang, Zhuyi Li
Myasthenia gravis (MG) is a rare prototypical autoimmune disorder caused by antibodies (Ab) against postsynaptic membrane proteins. Most reports have investigated the role of Autoimmune regulator gene (Aire) in thymic tissue in machianism of MG initiation. So far, the expression of Aire in human peripheral blood cells(we call it circulating Aire expression in the following passage) has not been reported. Herein, we explore the expression of Aire in peripharal blood, circulating T follicular helper (cTfh) and T follicular regulatory (cTfr) cells in MG patients...
May 17, 2018: Bioscience Reports
https://www.readbyqxmd.com/read/29769264/rhoa-g17v-is-sufficient-to-induce-autoimmunity-and-promotes-t-cell-lymphomagenesis-in-mice
#9
Samuel Y Ng, Leon Brown, Kristen Stevenson, Tiffany deSouza, Jon C Aster, Abner Louissaint, David M Weinstock
Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphomas commonly present with paraneoplastic autoimmunity and lymphopenia. RhoA G17V mutation is present in 60% of TFH-like lymphomas but its role in tumorigenesis is poorly understood. We generated transgenic mice that express RhoA G17V under the control of murine CD4 regulatory elements at levels comparable to a heterozygous mutation (tgRhoA mice)...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29757907/t-follicular-regulatory-cells-and-antibody-responses-in-transplantation
#10
E F Wallin
De novo donor specific antibody (DSA) formation is a major problem in transplantation, and associated with long-term graft decline and loss as well as sensitisation, limiting future transplant options. Forming high-affinity, long-lived antibody responses involves a process called the germinal center (GC) reaction, and requires interaction between several cell types, including GC B cells, T follicular helper (Tfh) and T follicular regulatory (Tfr) cells. Tfr cells are an essential component of the GC reaction, limiting its size and reducing nonspecific or self-reactive responses...
May 1, 2018: Transplantation
https://www.readbyqxmd.com/read/29751004/mutations-affecting-the-actin-regulator-wdr1-lead-to-aberrant-lymphoid-immunity
#11
Laurène Pfajfer, Nina K Mair, Raúl Jiménez-Heredia, Ferah Genel, Nesrin Gulez, Ömür Ardeniz, Birgit Hoeger, Sevgi Köstel Bal, Christoph Madritsch, Artem Kalinichenko, Rico Chandra Ardy, Bengü Gerçeker, Javier Rey-Barroso, Hanna Ijspeert, Stuart G Tangye, Ingrid Simonitsch-Klupp, Johannes B Huppa, Mirjam van der Burg, Loïc Dupré, Kaan Boztug
BACKGROUND: The actin-interacting protein WDR1 promotes cofilin-dependent actin filament turnover. Biallelic WDR1 mutations have recently been identified in an immunodeficiency/autoinflammatory syndrome with aberrant morphology and function of myeloid cells. OBJECTIVE: Given the pleiotropic expression of WDR1, we here investigated to what extent it might control the lymphoid arm of the immune system in humans. METHODS: Histological and detailed immunological analyses were performed to elucidate the role of WDR1 in development and function of B and T lymphocytes...
May 8, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29743369/intrastructural-help-harnessing-t-helper-cells-induced-by-licensed-vaccines-for-improvement-of-hiv-env-antibody-responses-to-virus-like-particle-vaccines
#12
Hassan Elsayed, Ghulam Nabi, William J McKinstry, Keith K Khoo, Johnson Mak, Andres M Salazar, Matthias Tenbusch, Vladimir Temchura, Klaus Überla
Induction of persistent antibody responses by vaccination is generally thought to depend on efficient help by T follicular helper cells. Since the T helper cell response to HIV Env may not be optimal, we explored the possibility to improve the HIV Env antibody response to virus-like particle (VLP) vaccines by recruiting T helper cells induced by a commonly-used licensed vaccines to provide help for Env-specific B cells. B cells specific for the surface protein of a VLP can internalize the entire VLP and thus present peptides derived from the surface and core proteins on their MHC-II molecules...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29743364/t-cell-derived-lymphotoxin-is-essential-for-anti-hsv-1-humoral-immune-response
#13
Kaiting Yang, Yong Liang, Zhichen Sun, Diyuan Xue, Hairong Xu, Mingzhao Zhu, Yang-Xin Fu, Hua Peng
B cell-derived lymphotoxin (LT) is required for the development of follicular dendritic cell clusters for the formation of primary and secondary lymphoid follicles, but the role of T cell-derived LT in antibody response has not been well demonstrated. We observed that lymphotoxin-β-receptor (LTβR) signaling is essential for optimal humoral immune response and protection against an acute HSV-1 infection. Blocking the LTβR pathway caused poor maintenance of germinal center B (GC-B) cells and follicular helper T (Tfh) cells...
May 9, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29743314/cd8-follicular-t-cells-promote-b-cell-antibody-class-switch-in-autoimmune-disease
#14
Kristen M Valentine, Dan Davini, Travis J Lawrence, Genevieve N Mullins, Miguel Manansala, Mufadhal Al-Kuhlani, James M Pinney, Jason K Davis, Anna E Beaudin, Suzanne S Sindi, David M Gravano, Katrina K Hoyer
CD8 T cells can play both a protective and pathogenic role in inflammation and autoimmune development. Recent studies have highlighted the ability of CD8 T cells to function as T follicular helper (Tfh) cells in the germinal center in the context of infection. However, whether this phenomenon occurs in autoimmunity and contributes to autoimmune pathogenesis is largely unexplored. In this study, we show that CD8 T cells acquire a CD4 Tfh profile in the absence of functional regulatory T cells in both the IL-2-deficient and scurfy mouse models...
May 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29741263/the-2017-who-update-on-mature-t-and-natural-killer-nk-cell-neoplasms
#15
REVIEW
E Matutes
Over the last decade, there has been a significant body of information regarding the biology of the lymphoid neoplasms. This clearly supports the need for updating the 2008 WHO (World Health Organization) classification of haematopoietic and lymphoid tumours. The 2017 WHO classification is not a new edition but an update and revision of the 4th edition. New provisional entities but not new definitive entities are included, and novel molecular data in most of the entities and changes in the nomenclature in few of them have been incorporated...
May 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29739909/a-high-frequency-of-hiv-specific-circulating-follicular-helper-t-cells-is-associated-with-preserved-memory-b-cell-responses-in-hiv-controllers
#16
M Claireaux, M Galperin, D Benati, A Nouël, M Mukhopadhyay, J Klingler, P de Truchis, D Zucman, S Hendou, F Boufassa, C Moog, O Lambotte, L A Chakrabarti
Follicular helper T cells (Tfh) play an essential role in the affinity maturation of the antibody response by providing help to B cells. To determine whether this CD4+ T cell subset may contribute to the spontaneous control of HIV infection, we analyzed the phenotype and function of circulating Tfh (cTfh) in patients from the ANRS CO21 CODEX cohort who naturally controlled HIV-1 replication to undetectable levels and compared them to treated patients with similarly low viral loads. HIV-specific cTfh (Tet+ ), detected by Gag-major histocompatibility complex class II (MHC-II) tetramer labeling in the CD45RA- CXCR5+ CD4+ T cell population, proved more frequent in the controller group ( P = 0...
May 8, 2018: MBio
https://www.readbyqxmd.com/read/29739835/nucleoside-modified-mrna-vaccines-induce-potent-t-follicular-helper-and-germinal-center-b-cell-responses
#17
Norbert Pardi, Michael J Hogan, Martin S Naradikian, Kaela Parkhouse, Derek W Cain, Letitia Jones, M Anthony Moody, Hans P Verkerke, Arpita Myles, Elinor Willis, Celia C LaBranche, David C Montefiori, Jenna L Lobby, Kevin O Saunders, Hua-Xin Liao, Bette T Korber, Laura L Sutherland, Richard M Scearce, Peter T Hraber, István Tombácz, Hiromi Muramatsu, Houping Ni, Daniel A Balikov, Charles Li, Barbara L Mui, Ying K Tam, Florian Krammer, Katalin Karikó, Patricia Polacino, Laurence C Eisenlohr, Thomas D Madden, Michael J Hope, Mark G Lewis, Kelly K Lee, Shiu-Lok Hu, Scott E Hensley, Michael P Cancro, Barton F Haynes, Drew Weissman
T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates...
May 8, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29734372/the-adaptor-molecule-cd2ap-in-cd4-t-cells-modulates-differentiation-of-follicular-helper-t-cells-during-chronic-lcmv-infection
#18
Saravanan Raju, Kohei Kometani, Tomohiro Kurosaki, Andrey S Shaw, Takeshi Egawa
CD4 T cell-mediated help to CD8 T cells and B cells is a critical arm of the adaptive immune system required for control of pathogen infection. CD4 T cells express cytokines and co-stimulatory molecules that support a sustained CD8 T cell response and also enhance generation of protective antibody by germinal center B cells. However, the molecular components that modulate CD4 T cell functions in response to viral infection or vaccine is incompletely understood. Here we demonstrate that inactivation of the signaling adaptor CD2-associated protein (CD2AP) promotes CD4 T cell differentiation towards the follicular helper lineage, leading to enhanced control of viral infection by augmented germinal center response in chronic lymphocytic choriomeningitis virus (LCMV) infection...
May 7, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29732234/microrna-mediated-regulation-of-the-development-and-functions-of-follicular-helper-t-cells
#19
REVIEW
Jeonghyun Lee, Hyosung Park, Jiyoung Eom, Seung Goo Kang
The germinal center reaction is a key event of humoral immunity, providing long-lived immunological memory. Follicular helper T (TFH ) cells are a specialized subset of CD4+ T cells located in the follicles, which help B cells and thus control the germinal center reaction. TFH cell development is achieved by multi-step processes of interactions with dendritic cells and B cells along with the coordination of various transcription factors. Since the T helper cell fate decision program is determined by subtle changes in regulatory molecules, fine tuning of these dynamic interactions is crucial for the generation functional TFH cells...
April 2018: Immune Network
https://www.readbyqxmd.com/read/29731996/microrna-signatures-and-foxp3-cell-count-correlate-with-relapse-occurrence-in-follicular-lymphoma
#20
Giorgio Malpeli, Stefano Barbi, Corinna Greco, Simonetta Zupo, Anna Bertolaso, Maria Teresa Scupoli, Mauro Krampera, Paul Takam Kamga, Carlo Maria Croce, Aldo Scarpa, Alberto Zamò
First line drug treatment of follicular lymphoma (FL) patients is followed by a highly variable disease-free time before relapse in about one third of patients. No molecular marker is able to predict efficiently the risk of relapse. We investigated the expression profile of microRNAs (miRNAs) by microarrays and of the tumor microenvironment by immunohistochemistry in 26 FLs and 12 reactive lymph nodes (rLN) as reference. Twenty-nine miRNAs were differentially expressed in FLs compared to rLNs and some of them discriminated grade 1 from 3a FLs...
April 13, 2018: Oncotarget
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