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Follicular helper T cells

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https://www.readbyqxmd.com/read/28322863/deep-immune-profiling-by-mass-cytometry-links-human-t-and-nk-cell-differentiation-and-cytotoxic-molecule-expression-patterns
#1
Bertram Bengsch, Takuya Ohtani, Ramin Sedaghat Herati, Niels Bovenschen, Kyong-Mi Chang, E John Wherry
The elimination of infected or tumor cells by direct lysis is a key T and NK cell effector function. T and NK cells can kill target cells by coordinated secretion of cytotoxic granules containing one or both pore-forming proteins, perforin and granulysin and combinations of granzyme (Gzm) family effector proteases (in humans: Gzm A, B, K, M and H). Understanding the pattern of expression of cytotoxic molecules and the relationship to different states of T and NK cells may have direct relevance for immune responses in autoimmunity, infectious disease and cancer...
March 17, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28319730/deconstructing-the-germinal-center-one-cell-at-a-time
#2
REVIEW
Chad R Dufaud, Louise J McHeyzer-Williams, Michael G McHeyzer-Williams
Successful vaccination relies on driving the immune response towards high specificity, affinity and longevity. Germinal centers facilitate the evolution of antigen-specific B cells by iterative rounds of diversification, selection, and differentiation to memory and plasma cells. Experimental evidence points to B cell receptor affinity and amount of antigen presented to follicular helper T cells as main drivers of clonal evolution. Concurrent studies suggest that modifiers of cognate contact, temporal mechanisms, and stochastic factors can also shape diversity and influence differentiation to memory and plasma cells, but molecular pathways driving these selection decisions are unresolved...
March 17, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319486/igg4-related-disease
#3
Emanuele Bozzalla Cassione, John H Stone
PURPOSE OF REVIEW: Remarkable insights have been gleaned recently with regard to the pathophysiology of IgG4-related disease (IgG4-RD). These findings have direct implications for the development of targeted strategies for the treatment of this condition. RECENT FINDINGS: Oligoclonal expansions of cells of both the B and T lymphocyte lineages are present in the blood of patients with IgG4-RD. Oligoclonal expansions of plasmablasts are a good biomarker for disease activity...
March 17, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28303495/genetic-landscape-and-classification-of-peripheral-t-cell-lymphomas
#4
REVIEW
Rosalind F Sandell, Rebecca L Boddicker, Andrew L Feldman
PURPOSE OF REVIEW: Peripheral T cell lymphomas (PTCLs) are markedly heterogeneous at the clinical, pathological, and molecular levels. This review will discuss genetic findings in PTCL with special emphasis on how they impact lymphoma classification. RECENT FINDINGS: Sequencing studies have identified recurrent genetic alterations in nearly every PTCL subtype. In anaplastic large cell lymphoma, these studies have revealed novel chromosomal rearrangements and mutations that have prognostic significance and may suggest new therapeutic approaches...
April 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28299186/recent-advances-in-understanding-and-managing-igg4-related-disease
#5
REVIEW
Anna R Wolfson, Daniel L Hamilos
IgG4-related disease was only recently discovered, so its description, management, and new discoveries related to its etiology are rapidly evolving. Because IgG4 itself is a unique antibody which is intimately related to the diagnosis of the disease, the role of plasmablasts in the pathophysiology remains an active area of discussion. Recent studies have uncovered a possible role for CD4-positive cytotoxic T lymphocytes, T follicular helper cells, and M2 macrophages. The clinical presentation is variable and can be vague, as this disease affects many organs and new presentations are continuing to be described...
2017: F1000Research
https://www.readbyqxmd.com/read/28298605/cxcr5-dependent-entry-of-cd8-t-cells-into-rhesus-macaque-b-cell-follicles-achieved-through-t-cell-engineering
#6
Victor I Ayala, Claire Deleage, Matthew T Trivett, Sumiti Jain, Lori V Coren, Matthew W Breed, Joshua A Kramer, James A Thomas, Jacob D Estes, Jeffrey D Lifson, David E Ott
Follicular helper CD4 T cells, TFH, residing in B-cell follicles within secondary lymphoid tissues, are readily infected by AIDS viruses and are a major source of persistent virus despite relative control of viral replication. This persistence is due at least in part to a relative exclusion of effective antiviral CD8 T cells from B-cell follicles. To determine whether CD8 T cells could be engineered to enter B-cell follicles, we genetically modified unselected CD8 T cells to express CXCR5, the chemokine receptor implicated in cellular entry into B-cell follicles...
March 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28297661/t-follicular-helper-cells-promote-a-beneficial-gut-ecosystem-for-host-metabolic-homeostasis-by-sensing-microbiota-derived-extracellular-atp
#7
Lisa Perruzza, Giorgio Gargari, Michele Proietti, Bruno Fosso, Anna Maria D'Erchia, Caterina Elisa Faliti, Tanja Rezzonico-Jost, Daniela Scribano, Laura Mauri, Diego Colombo, Giovanni Pellegrini, Annalisa Moregola, Catherine Mooser, Graziano Pesole, Mauro Nicoletti, Giuseppe Danilo Norata, Markus B Geuking, Kathy D McCoy, Simone Guglielmetti, Fabio Grassi
The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer's patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28289412/follicular-t-cells-from-smb-common-variable-immunodeficiency-patients-are-skewed-toward-a-th1-phenotype
#8
Vanesa Cunill, Antonio Clemente, Nallibe Lanio, Carla Barceló, Valero Andreu, Jaume Pons, Joana M Ferrer
Germinal center follicular T helper (GCTfh) cells are essential players in the differentiation of B cells. Circulating follicular T helper (cTfh) cells share phenotypic and functional properties with GCTfh cells. Distinct subpopulations of cTfh with different helper capabilities toward B cells can be identified: cTfh1 (CXCR3(+)CCR6(-)), cTfh2 (CXCR3(-)CCR6(-)), and cTfh17 (CXCR3(-)CCR6(+)). Alterations in cTfh function and/or distribution have been associated with autoimmunity, infectious diseases, and more recently, with several monogenic immunodeficiencies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28287825/quantification-of-residual-germinal-center-activity-and-hiv-1-dna-and-rna-levels-using-fine-needle-biopsies-of-lymph-nodes-during-antiretroviral-therapy
#9
William J Hey-Nguyen, Yin Xu, Chester F Pearson, Michelle Bailey, Kazuo Suzuki, Robyn Tantau, Solange Obeid, Brad Milner, Andrew Field, Andrew Carr, Mark Bloch, David A Cooper, Anthony D Kelleher, John J Zaunders, Kersten K Koelsch
HIV-1 reservoirs are most often studied in peripheral blood (PB), but not all lymphocytes recirculate, particularly T follicular helper (Tfh) CD4(+) T cells, as well as germinal center (GC) B cells, in lymph nodes (LNs). Ultrasound-guided fine needle biopsies (FNBs) from inguinal LNs and PB samples were obtained from 10 healthy controls (HCs) and 21 HIV-1-infected subjects [11 antiretroviral therapy (ART) naive and 10 on ART]. Tfh cells and GC B cells were enumerated by flow cytometry. HIV-1 DNA and cell-associated (CA) RNA levels in LNs and PB were quantified by real-time polymerase chain reaction...
March 13, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28281408/the-role-of-follicular-t-helper-cells-in-patients-with-malignant-lymphoid-disease
#10
Dong-Ming Zhou, Yan-Xia Xu, Li-Ying Zhang, Yu Sun, Zi-Yan Wang, Yu-Qing Yuan, Jin-Xiang Fu
OBJECTIVES: To investigate the dynamic change of follicular T helper cells (TFH) in patients with malignant lymphoid disease (MLD) and to explore its clinical significance. METHODS: The dynamic change of TFH cells, ICOS(+)- and PD-1(+) TFH cells at pretreatment and different treatment periods was determined by flow cytometry in 85 MLD patients. Concentration of interleukin 21 (IL-21) was evaluated by ELISA, and the correlation between clinical prognosis and the ratio of TFH cells was analyzed...
March 10, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/28279590/transcription-factor-t-bet-orchestrates-lineage-development-and-function-in-the-immune-system
#11
REVIEW
Axel Kallies, Kim L Good-Jacobson
T-bet was originally described as the key transcription factor defining type 1 T helper (Th) cells. However, it is now clear that it drives the orchestrated generation of effector and memory cells in multiple different lymphocyte lineages. In addition to Th1 cells, CD8 T cells, B cells and some innate lymphocyte populations require T-bet for their development or differentiation in response to antigen. Furthermore, other Th cell populations, including T follicular helper and Th17, as well as regulatory T cells can co-opt T-bet expression to promote functional diversification and colocalization...
March 6, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28274850/direct-acting-antiviral-therapy-restores-immune-tolerance-to-patients-with-hepatitis-c-virus-induced-cryoglobulinemia-vasculitis
#12
Cloé Comarmond, Marlène Garrido, Stanislas Pol, Anne-Claire Desbois, Myrto Costopoulos, Magali Le Garff-Tavernier, Si Nafa Si Ahmed, Laurent Alric, Hélène Fontaine, Bertrand Bellier, Anna Maciejewski, Michelle Rosenzwajg, David Klatzmann, Lucile Musset, Thierry Poynard, Patrice Cacoub, David Saadoun
BACKGROUND & AIMS: Interferon-free direct-acting antiviral (DAA) therapies are effective in patients with hepatitis C virus-induced cryoglobulinemia vasculitis (HCV-CV). We analyzed blood samples from patients with HCV-CV before and after DAA therapy to determine mechanisms of these drugs and their effects on cellular immunity. METHODS: We performed a prospective study of 27 consecutive patients with HCV-CV (median age 59 years) treated with DAA therapy (21 patients received sofosbuvir plus ribavirin for 24 weeks, 4 patients received sofosbuvir plus daclatasvir for 12 weeks, and 2 patients received sofosbuvir plus simeprevir for 12 weeks) in Paris, France...
March 5, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28265271/cd4-t-follicular-helper-cells-and-hiv-infection-friends-or-enemies
#13
REVIEW
Félicien Moukambi, Vasco Rodrigues, Yasmina Fortier, Henintsoa Rabezanahary, Chloé Borde, Bernard Krust, Guadalupe Andreani, Ricardo Silvestre, Constantinos Petrovas, Mireille Laforge, Jérôme Estaquier
Follicular T helper (Tfh) cells, a subset of CD4 T lymphocytes, are essential for memory B cell activation, survival, and differentiation and assist B cells in the production of antigen-specific antibodies. Work performed in recent years pointed out the importance of Tfh cells in the context of HIV and SIV infections. The importance of tissue distribution of Tfh is also an important point since their frequency differs between peripheral blood and lymph nodes compared to the spleen, the primary organ for B cell activation, and differentiation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28263097/transcriptional-and-epigenetic-regulation-of-follicular-t-helper-cells-and-their-role-in-autoimmunity
#14
Hong Qiu, Haijing Wu, Vera Chan, Chak-Sing Lau, Qianjin Lu
T-follicular helper (Tfh) cells are a specialized subset of T cells that provide help to B cells and promote the formation of germinal centers (GCs). Tfh cells transmit important signals to B cells that drive class switch recombination, somatic hyper-mutation, the generation of high-affinity antibodies, immunological memory and their differentiation into plasma cells or memory B cells in the GCs. Tfh-cell differentiation is regulated by the coordinated functions of distinct cytokines, including interleukin (IL)-6, IL-21, IL-12, IL-23, IL-2, IL-7 and transforming growth factor-β (TGF-β), as well as transcription factors, including B-cell lymphoma 6 protein (Bcl-6), Signal transducers and activators of transcription (STAT)1, STAT3, STAT4, B-cell activating transcription factor (Batf), interferon regulatory factor 4 (IRF4), v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog (C-Maf), T-cell-specific transcription factor 1 (TCF-1) and Achaete-scute homolog 2 (Acl2), which have been shown to form a complex transcriptional network...
March 2017: Autoimmunity
https://www.readbyqxmd.com/read/28257976/the-pbx1-lupus-susceptibility-gene-regulates-cd44-expression
#15
Yuxin Niu, Mayami Sengupta, Anton A Titov, Seung-Chul Choi, Laurence Morel
PBX1-d is novel splice isoform of pre-B-cell leukemia homeobox 1 (PBX1) that lacks its DNA-binding and Hox-binding domains, and functions as a dominant negative. We have shown that PBX1-d expression in CD4(+) T cells is associated with systemic lupus erythematosus (SLE) in a mouse model as well as in human subjects. More specifically, PBX1-d expression leads to the production of autoreactive activated CD4+ T cells, a reduced frequency and function of Foxp3+ regulatory T (Treg) cells and an expansion of follicular helper T (Tfh) cells...
February 28, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28254742/pirfenidone-ameliorates-murine-chronic-gvhd-through-inhibition-of-macrophage-infiltration-and-tgf-%C3%AE-production
#16
Jing Du, Katelyn Paz, Ryan Flynn, Ante Vulic, Tara M Robinson, Katie E Lineburg, Kylie A Alexander, Jingjing Meng, Sabita Roy, Angela Panoskaltsis-Mortari, Michael Loschi, Geoffrey R Hill, Jonathan S Serody, Ivan Maillard, David Miklos, John Koreth, Corey S Cutler, Joseph H Antin, Jerome Ritz, Kelli P MacDonald, Timothy W Schacker, Leo Luznik, Bruce R Blazar
Allogeneic hematopoietic stem cell transplantation is hampered by chronic graft-versus-host disease (cGVHD) resulting in multi-organ fibrosis and diminished function. Fibrosis in lung and skin leads to progressive bronchiolitis obliterans (BO) and scleroderma, respectively, for which new treatments are needed. We evaluated pirfenidone, a FDA approved drug for idiopathic pulmonary fibrosis, for its therapeutic effect in cGVHD mouse models with distinct pathophysiology. In a full MHC-mismatched, multi-organ system model with BO, donor T cell responses that support pathogenic antibody production are required for cGVHD development...
March 2, 2017: Blood
https://www.readbyqxmd.com/read/28250157/il-6-production-by-tlr-activated-apc-broadly-enhances-aged-cognate-cd4-helper-and-b-cell-antibody-responses-in-vivo
#17
Vinayak Brahmakshatriya, Yi Kuang, Priyadharshini Devarajan, Jingya Xia, Wenliang Zhang, Allen Minh Vong, Susan L Swain
Naive CD4 T cell responses, especially their ability to help B cell responses, become compromised with aging. We find that using APC pretreated ex vivo with TLR agonists, polyinosinic-polycytidylic acid and CpG, to prime naive CD4 T cells in vivo, restores their ability to expand and become germinal center T follicular helpers and enhances B cell IgG Ab production. Enhanced helper responses are dependent on IL-6 production by the activated APC. Aged naive CD4 T cells respond suboptimally to IL-6 compared with young cells, such that higher doses are required to induce comparable signaling...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28242651/metformin-suppresses-systemic-autoimmunity-in-roquin-san-san-mice-through-inhibiting-b-cell-differentiation-into-plasma-cells-via-regulation-of-ampk-mtor-stat3
#18
Seon-Yeong Lee, Su-Jin Moon, Eun-Kyung Kim, Hyeon-Beom Seo, Eun-Ji Yang, Hye-Jin Son, Jae-Kyung Kim, Jun-Ki Min, Sung-Hwan Park, Mi-La Cho
Circulating autoantibodies and immune complex deposition are pathological hallmarks of systemic lupus erythematosus (SLE). B cell differentiation into plasma cells (PCs) and some T cell subsets that function as B cell helpers can be therapeutic targets of SLE. Mechanistic target of rapamycin (mTOR) signaling is implicated in the formation of B cells and germinal centers (GCs). We assessed the effect of metformin, which inhibits mTOR, on the development of autoimmunity using Roquin(san/san) mice. Oral administration of metformin inhibited the formation of splenic follicles and inflammation in kidney and liver tissues...
April 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28231392/from-dendritic-cells-to-b-cells-dysfunctions-during-hiv-1-infection-tfh-at-the-cross-road
#19
REVIEW
Nicolas Ruffin, Lylia Hani, Nabila Seddiki
T follicular helper (Tfh) cells are essential for B cell differentiation and the subsequent antibody responses. Their numbers and functions are altered during human and simian immunodeficiency virus (HIV/SIV) infections. In lymphoid tissues, Tfh cells are present in germinal center, where they are the main source of replicative HIV-1 and represent a major reservoir. Paradoxically, Tfh numbers are increased in chronically infected individuals. Understanding the fate of Tfh cells in the course of HIV-1 infection is essential for the design of efficient strategies toward a protective HIV vaccine or a cure...
February 23, 2017: Immunology
https://www.readbyqxmd.com/read/28228602/a-divergent-population-of-autoantigen-responsive-cd4-t-cells-in-infants-prior-to-%C3%AE-cell-autoimmunity
#20
Anne-Kristin Heninger, Anne Eugster, Denise Kuehn, Florian Buettner, Matthias Kuhn, Annett Lindner, Sevina Dietz, Sibille Jergens, Carmen Wilhelm, Andreas Beyerlein, Anette-G Ziegler, Ezio Bonifacio
Autoimmune diabetes is marked by sensitization to β cell self-antigens in childhood. We longitudinally followed at-risk children from infancy and performed single-cell gene expression in β cell antigen-responsive CD4(+) T cells through pre- and established autoimmune phases. A striking divergence in the gene signature of β cell antigen-responsive naïve CD4(+) T cells from children who developed β cell autoimmunity was found in infancy, well before the appearance of β cell antigen-specific memory T cells or autoantibodies...
February 22, 2017: Science Translational Medicine
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