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T helper cell and lymphoma

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https://www.readbyqxmd.com/read/27933753/mass-cytometry-of-follicular-lymphoma-tumors-reveals-intrinsic-heterogeneity-in-proteins-including-hla-dr-and-a-deficit-in-non-malignant-plasmablast-and-germinal-center-b-cell-populations
#1
Cara Ellen Wogsland, Allison Rae Greenplate, Arne Kolstad, June Helen Myklebust, Jonathan Michael Irish, Kanutte Huse
BACKGROUND: Follicular lymphoma (FL) is an indolent non-Hodgkin lymphoma that has a risk of transformation to more aggressive lymphoma. Relatively little is known about the non-malignant B-cell and T-cell subset composition within the tumor microenvironment and whether altered phenotypes are associated with patterns of lymphoma B-cell heterogeneity. METHODS: Two mass cytometry (CyTOF) panels were designed to immunophenotype B and T cells in FL tumors. Populations of malignant B cells, non-malignant B cells, and T cells from each FL tumor were identified and their phenotypes compared to B and T cells from healthy human tonsillar tissue...
December 9, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933060/regulators-of-tfh-cell-differentiation
#2
REVIEW
Gajendra M Jogdand, Suchitra Mohanty, Satish Devadas
The follicular helper T (Tfh) cells help is critical for activation of B cells, antibody class switching, and germinal center (GC) formation. The Tfh cells are characterized by the expression of CXC chemokine receptor 5 (CXCR5), ICOS, programed death 1 (PD-1), B cell lymphoma 6 (BCL-6), and IL-21. They are involved in clearing infections and are adversely linked with autoimmune diseases and also have a role in viral replication as well as clearance. On the one hand, Tfh cells are generated from naive CD4(+) T cells with sequential steps involving cytokine signaling (IL-21, IL-6, IL-12, activin A), migration, and positioning in the GC by CXCR5, surface receptors (ICOS/ICOSL, signaling lymphocyte activation molecule-associated protein/signaling lymphocyte activation molecule) as well as transcription factor (BCL-6, c-Maf, and signal transducer and activator of transcription 3) signaling and repressor miR155...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27921272/bcl6-locus-is-hypermethylated-in-angioimmunoblastic-t-cell-lymphoma
#3
Shoko Nishizawa, Mamiko Sakata-Yanagimoto, Keiichiro Hattori, Hideharu Muto, Tran Nguyen, Koji Izutsu, Kenichi Yoshida, Seishi Ogawa, Naoya Nakamura, Shigeru Chiba
BCL6, a master transcription factor for differentiation of follicular helper T (TFH) cells, is highly expressed in angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphomas (PTCL) containing tumor cells with TFH features. TET2, encoding an epigenetic regulator, is frequently mutated in AITL/PTCL. We previously reported that Tet2 knockdown mice developed T-cell lymphomas with TFH features. Hypermethylation of the Bcl6 locus followed by BCL6 upregulation was thought to be the key event for lymphoma development in mice...
December 5, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27888017/circulating-cxcr5-cd4-t-cells-assist-in-the-survival-and-growth-of-primary-diffuse-large-b-cell-lymphoma-cells-through-interleukin-10-pathway
#4
Zhanshan Cha, Guangfang Qian, Yan Zang, Haihui Gu, Yanyan Huang, Lishuang Zhu, Jinqi Li, Yang Liu, Xiaohua Tu, Haihan Song, Baohua Qian
Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5(+) CD4(+) T cells, in DLBCL. Data showed that compared to CXCR5(-) CD4(+) T cells, CXCR5(+) CD4(+) T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells...
November 23, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/27863842/development-of-t-follicular-helper-cells-and-their-role-in-disease-and-immune-system
#5
REVIEW
Sadegh Eivazi, Salman Bagheri, Mohammad Sadegh Hashemzadeh, Majdedin Ghalavand, Elmira Safaie Qamsari, Ruhollah Dorostkar, Maryam Yasemi
The T follicular helper cells (TFH) are a subset of CD4+ T cells specialized to regulate antibody responses. The production of these cells is associated with the dendritic cells (DCs) and B cells. TFH cells help B cells form germinal centers (GC) differentiate into memory and plasma cells (antibody-secreting cells) as humoral responses. In addition, there is strong evidence that TFH cells play a pivotal role in the development of long-lived humoral immunity. Molecular factors such as transcription factors, surface receptors, cytokine and micro RNAs are involved in the formation of TFH cells...
November 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27861791/foxp1-is-a-key-regulator-of-quiescence-in-healthy-human-cd3-cd4-t-cells-and-is-constitutively-repressed-in-cd3-cd4-t-cells-from-patients-with-lymphoproliferative-disorders
#6
Soizic Garaud, Florence Roufosse, Pushpamali De Silva, Chunyan Gu-Trantien, Jean-Nicolas Lodewyckx, Hugues Duvillier, Sarah Dedeurwaerder, Martin Bizet, Matthieu Defrance, François Fuks, Françoise Bex, Karen Willard-Gallo
The forkhead box P1 (FOXP1) transcription factor has been shown to regulate the generation and maintenance of quiescent naïve murine T cells. In humans, FOXP1 expression has been correlated with overall survival in patients with peripheral T-cell lymphoma (PTCL), although its regulatory role in T-cell function is currently unknown. We found that FOXP1 is normally expressed in all human leukocyte subpopulations. Focusing on primary human CD4(+) T cells, we show that nuclear expression of FOXP1 predominates in naïve cells with significant downregulation detected in memory cells from blood and tonsils...
November 8, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27818202/the-expression-of-bcl-6-in-circulating-follicular-helper-like-t-cells-positively-correlates-with-the-disease-activity-in-systemic-lupus-erythematosus
#7
Xin Huang, Haijing Wu, Hong Qiu, Huilan Yang, Yaxiong Deng, Ming Zhao, Hairong Luo, Xiang Zhou, Yubin Xie, Vera Chan, Chak-Sing Lau, Qianjin Lu
Increased circulating follicular helper-like T cells (cTfh) are reported in systemic lupus erythematosus (SLE) patients. However, whether B-cell lymphoma 6 (Bcl-6) is expressed in cTfh cells remains to be clarified. In this study, we found that the frequencies of CD4(+)CXCR5(hi)PD-1(hi)cTfh, CD4(+)CXCR5(hi)PD-1(hi)ICOS(hi), and CD4(+)CXCR5(hi)PD-1(hi)Bcl-6(+) populations were significantly increased in SLE patients (n=70) when compared with healthy controls (n=48). Surprisingly, only CD4(+)CXCR5(hi)PD-1(hi)Bcl-6(+) cTfh cells, rather than CD4(+)CXCR5(hi)PD-1(hi) population, were positively correlated with SLEDAI and anti-dsDNA antibodies...
December 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27693350/loss-of-the-hvem-tumor-suppressor-in-lymphoma-and-restoration-by-modified-car-t-cells
#8
Michael Boice, Darin Salloum, Frederic Mourcin, Viraj Sanghvi, Rada Amin, Elisa Oricchio, Man Jiang, Anja Mottok, Nicolas Denis-Lagache, Giovanni Ciriello, Wayne Tam, Julie Teruya-Feldstein, Elisa de Stanchina, Wing C Chan, Sami N Malek, Daisuke Ennishi, Renier J Brentjens, Randy D Gascoyne, Michel Cogné, Karin Tarte, Hans-Guido Wendel
The HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in germinal center lymphomas. We report that loss of HVEM leads to cell-autonomous activation of B cell proliferation and drives the development of GC lymphomas in vivo. HVEM-deficient lymphoma B cells also induce a tumor-supportive microenvironment marked by exacerbated lymphoid stroma activation and increased recruitment of T follicular helper (TFH) cells. These changes result from the disruption of inhibitory cell-cell interactions between the HVEM and BTLA (B and T lymphocyte attenuator) receptors...
October 6, 2016: Cell
https://www.readbyqxmd.com/read/27634753/adoptive-transfer-of-tumor-specific-th2-cells-eradicates-tumors-by-triggering-an-in-situ-inflammatory-immune-response
#9
Kristina Berg Lorvik, Clara Hammarström, Marte Fauskanger, Ole Audun Werner Haabeth, Michael Zangani, Guttorm Haraldsen, Bjarne Bogen, Alexandre Corthay
Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8(+) T cells; however, the potential of CD4(+) T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with IFNγ-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with MHC class II-negative myeloma...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27596815/angioimmunoblastic-t-cell-lymphoma-with-a-clonal-plasma-cell-proliferation-that-underwent-immunoglobulin-isotype-switch-in-the-skin-coinciding-with-cutaneous-disease-progression
#10
Ana E Suárez, M J Artiga, Carlos Santonja, Santiago Montes-Moreno, P De Pablo, Luis Requena, Miguel A Piris, Socorro M Rodríguez-Pinilla
Plasma cell proliferations in specific cutaneous lesions of angioimmunoblastic T-cell lymphoma(AITL) are very uncommon. Here, we report a case of clonal plasma cell proliferation in skin with heavy-chain-immunoglobulin-isotype-switch after cutaneous disease progression. Histopathologically, initial plaque lesions were suggestive of marginal-zone B-cell-lymphoma. Nevertheless, this 77-year-old lady was diagnosed with AITL after the progression of skin lesions from plaques to nodular tumors. A lymph node biopsy confirmed the diagnosis...
December 2016: Journal of Cutaneous Pathology
https://www.readbyqxmd.com/read/27556734/il-31-driven-skin-remodeling-involves-epidermal-cell-proliferation-and-thickening-that-lead-to-impaired-skin-barrier-function
#11
Brijendra Singh, Anil G Jegga, Kumar S Shanmukhappa, Ramakrishna Edukulla, Gurjit H Khurana, Mario Medvedovic, Stacey R Dillon, Satish K Madala
Interleukin-31 (IL-31) is a type 2 helper T-cell-derived cytokine that has recently been shown to cause severe inflammation and tissue remodeling in multiple chronic diseases of the skin and lungs. IL-31 is upregulated in allergic and inflammatory diseases, including atopic dermatitis, asthma, cutaneous T-cell lymphomas, and allergic rhinitis, as well as autoimmune diseases such as systemic erythematosus. Overexpression of IL-31 in T cells causes severe inflammation, with histological features similar to skin lesions of patients with atopic dermatitis...
2016: PloS One
https://www.readbyqxmd.com/read/27524795/differences-in-tfh-cell-response-between-the-graft-and-spleen-with-chronic-allograft-nephropathy
#12
Jian Shi, Xianlin Xu, Fengbao Luo, Qianqian Shi, Xiaozhou He, Ying Xia
The aim of this study was to investigate follicular helper T (Tfh) cell response and its difference between renal graft and spleen in a rat renal transplantation model undergoing chronic allograft nephropathy (CAN). Orthotopical kidney transplantations were performed on Fischer (F344) rats and transplanted to Lewis rats, using syngeneic Lewis-Lewis grafts as controls. Tissue samples were collected at 8 weeks post-transplantation. The status of Tfh cell response was assessed by measuring the levels of transcription factor B-cell lymphoma 6 (Bcl-6), interleukin 21 (IL-21), chemokine receptor type 5 (CXCR5), and B cell activating factor belonging to the TNF family (BAFF)...
August 12, 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27504608/dedicator-of-cytokinesis-2-in-cell-signaling-regulation-and-disease-development
#13
Xia Guo, Shi-You Chen
Dedicator of cytokinesis 2 (DOCK2) is a CDM family protein containing DOCK homology region (DHR) -1 and DHR-2, Src-homology 3 (SH3) domain, and C-terminal polybasic amino acid cluster. The CDM family consists of 11 mammalian members and is classified into four subfamilies, the DOCK-A, -B, -C, and -D. DOCK2 is a member of DOCK-A subfamily and an atypical guanine exchange factor regulating the loading of GTP to activate Rac. It is primarily found in peripheral blood, spleen, and thymus and mainly expressed in lymphocytes and macrophages of various organs...
August 9, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27489357/increased-frequency-of-circulating-th22-cells-in-patients-with-b-cell-non-hodgkin-s-lymphoma
#14
Ting Lu, Yan Liu, Shuang Yu, Congcong Yin, Peng Li, Jingjing Ye, Daoxin Ma, Chunyan Ji
T helper (Th) 22 cells play important roles in the pathogenesis of autoimmune and inflammatory diseases, and their function in tumors remains uncertain. In the current study, we investigated the alternations and clinical significance of circulating Th22 cells in patients with B-cell non-Hodgkin's lymphoma (B-NHL). We found that the frequency of Th22 cells was significantly elevated in peripheral blood of newly-diagnosed B-NHL patients, and returned to normal level after chemotherapy. In consistent with increased Th22 frequency, plasma IL-22 and IL-6 levels in B-NHL patients were remarkably increased...
July 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27436361/rock2-signaling-is-required-to-induce-a-subset-of-t-follicular-helper-cells-through-opposing-effects-on-stats-in-autoimmune-settings
#15
Jonathan M Weiss, Wei Chen, Melanie S Nyuydzefe, Alissa Trzeciak, Ryan Flynn, James R Tonra, Suzana Marusic, Bruce R Blazar, Samuel D Waksal, Alexandra Zanin-Zhorov
Rho-associated kinase 2 (ROCK2) determines the balance between human T helper 17 (TH17) cells and regulatory T (Treg) cells. We investigated its role in the generation of T follicular helper (TFH) cells, which help to generate antibody-producing B cells under normal and autoimmune conditions. Inhibiting ROCK2 in normal human T cells or peripheral blood mononuclear cells from patients with active systemic lupus erythematosus (SLE) decreased the number and function of TFH cells induced by activation ex vivo. Moreover, inhibition of ROCK2 activity decreased the abundance of the transcriptional regulator Bcl6 (B cell lymphoma 6) and increased that of Blimp1 by reducing the binding of signal transducer and activator of transcription 3 (STAT3) and increasing that of STAT5 to the promoters of the genes Bcl6 and PRDM1, respectively...
July 19, 2016: Science Signaling
https://www.readbyqxmd.com/read/27428734/a-clinicopathologic-study-of-lennert-lymphoma-and-possible-prognostic-factors-the-importance-of-follicular-helper-t-cell-markers-and-the-association-with-angioimmunoblastic-t-cell-lymphoma
#16
Daisuke Kurita, Hiroaki Miyoshi, Noriaki Yoshida, Yuya Sasaki, Seiichi Kato, Daisuke Niino, Yasuo Sugita, Yoshihiro Hatta, Masami Takei, Makoto Makishima, Koichi Ohshima
Lennert lymphoma (LeL) is a variant of peripheral T-cell lymphoma, not otherwise specified. Few clinicopathologic studies have investigated LeL, which is a rare disease. Here, we analyzed the clinicopathologic features of 26 patients with LeL to identify potential prognostic factors. Neoplastic cells positive for CD4, CD8, CD4/CD8, TIA-1, and granzyme B were observed in 21 (80.8%), 4 (15.4%), 1 (3.8%), 4 (15.3%), and 0 (0.0%) patients, respectively. Regarding follicular helper T-cell (TFH) markers, neoplastic cells positive for programmed cell death-1 (PD-1), CXCL13, CD10, and BCL6 were observed in 14 (53...
September 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27369867/activating-mutations-in-genes-related-to-tcr-signaling-in-angioimmunoblastic-and-other-follicular-helper-t-cell-derived-lymphomas
#17
David Vallois, Maria Pamela D Dobay, Ryan D Morin, François Lemonnier, Edoardo Missiaglia, Mélanie Juilland, Justyna Iwaszkiewicz, Virginie Fataccioli, Bettina Bisig, Annalisa Roberti, Jasleen Grewal, Julie Bruneau, Bettina Fabiani, Antoine Martin, Christophe Bonnet, Olivier Michielin, Jean-Philippe Jais, Martin Figeac, Olivier A Bernard, Mauro Delorenzi, Corinne Haioun, Olivier Tournilhac, Margot Thome, Randy D Gascoyne, Philippe Gaulard, Laurence de Leval
Angioimmunoblastic T-cell lymphoma (AITL) and other lymphomas derived from follicular T-helper cells (TFH) represent a large proportion of peripheral T-cell lymphomas (PTCLs) with poorly understood pathogenesis and unfavorable treatment results. We investigated a series of 85 patients with AITL (n = 72) or other TFH-derived PTCL (n = 13) by targeted deep sequencing of a gene panel enriched in T-cell receptor (TCR) signaling elements. RHOA mutations were identified in 51 of 85 cases (60%) consisting of the highly recurrent dominant negative G17V variant in most cases and a novel K18N in 3 cases, the latter showing activating properties in in vitro assays...
September 15, 2016: Blood
https://www.readbyqxmd.com/read/27369070/long-term-follow-up-and-management-of-small-and-medium-sized-cd4-t-cell-lymphoma-and-cd8-lymphoid-proliferations-of-acral-sites-a-multicenter-experience
#18
Pooja Virmani, Sarah Jawed, Patricia L Myskowski, Steven Horwitz, Anna Skripnik Lucas, Alison Moskowitz, Melissa Pulitzer, Jasmine Zain, Steven T Rosen, Christiane Querfeld
BACKGROUND: Primary cutaneous CD4(+) small-medium pleomorphic T cell lymphoma (SMPTCL) is a low-grade cutaneous T cell lymphoma. Its clinical and histopathologic features are comparable with those of CD8(+) lymphoid proliferations (LPs) of the ear and acral sites. OBJECTIVES: We performed a retrospective analysis of patients with CD4(+) SMPTCL or CD8(+) LP to elucidate the clinical course, prognosis, and outcomes. METHODS: Demographic, clinical, and treatment data were reviewed...
November 2016: International Journal of Dermatology
https://www.readbyqxmd.com/read/27364124/interleukin-9-promotes-cell-survival-and-drug-resistance-in-diffuse-large-b-cell-lymphoma
#19
Xiao Lv, Lili Feng, Xueling Ge, Kang Lu, Xin Wang
BACKGROUND: Interleukin-9 (IL-9) was discovered as a helper T cell growth factor. It has long been recognized as an important regulator in allergic inflammation. Recent years it was discovered to induce cell growth and differentiation of multiple transformed cells. However, its oncogenic activities in B-cell lymphomas have not been reported in detail. METHODS: Serum levels of IL-9 in DLBCL patients were quantified by ELISA, and its clinical significance was analysed...
2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27334853/follicular-lymphoma-the-role-of-the-tumor-microenvironment-in-prognosis
#20
Takumi Sugimoto, Takashi Watanabe
The microenvironment of follicular lymphoma (FL) is composed of tumor-infiltrating CD8(+) T cells, follicular regulatory T cells, lymphoma-associated macrophages and mast cells, follicular helper T cells, follicular dendritic cells, and follicular reticular cells, all of which have been reported to have relevance in the prognosis of FL patients. In addition, some of these cells play a role in the histologic transformation of FL. Macrophages contribute to a poor prognosis in FL patients treated in the pre-rituximab era, but are associated with good prognosis in those treated in the rituximab era...
2016: Journal of Clinical and Experimental Hematopathology: JCEH
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