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T helper cell and B cell lymphoma

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https://www.readbyqxmd.com/read/28656528/chitinase-3-like-1-deficient-splenocytes-deteriorated-the-pathogenesis-of-acute-graft-versus-host-disease-via-regulating-differentiation-of-tfh-cells
#1
Zengyao Li, Hao Lu, Jian Gu, Jing Liu, Qin Zhu, Yunjie Lu, Xuehao Wang
Acute graft-versus-host disease (aGVHD) is an intractable complication in transplant patients, limiting the efficacy of this therapy. Chitinase 3-like-1 (CHI3L1), a member of the glycosyl hydrolase 18 family that lacks chitinase activity, plays a critical role in a variety of inflammatory diseases. Here, we investigated the in vitro and in vivo effects of CHI3L1 on the development of aGVHD. In this study, mixed lymphocyte reactions (MLR) in vitro showed that CHI3L1 deficiency in CD4(+) T cell promoted the production of interferon (IFN)-γ and T follicular helper (Tfh)-related cytokines such as interleukin-6 (IL-6) and interleukin-21 (IL-21)...
June 27, 2017: Inflammation
https://www.readbyqxmd.com/read/28543514/angioimmunoblastic-t-cell-lymphoma-more-than-a-disease-of-t-follicular-helper-cells
#2
François Lemonnier, Tak W Mak
Angioimmunoblastic T cell lymphoma (AITL) is one of the most frequent entities of peripheral T cell lymphoma. An AITL has two components: the AITL tumor cells that have a T follicular helper (TFH) cell phenotype, and a surrounding and extensive tumor microenvironment that is populated with various reactive cell types, including B cells. Recurrent TET2 mutations have been described in 50-80% of AITLs, possibly occurring in a hematopoietic progenitor cell. An article published recently in The Journal of Pathology describes the use of microdissection to isolate PD1(+) AITL tumor cells and CD20(+) B cells from the AITL microenvironment and to show that TET2 mutations are actually more frequent in these diseases than previously thought...
May 24, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28439064/immunotherapy-of-dual-function-vector-with-both-immunostimulatory-and-b-cell-lymphoma-2-bcl-2-silencing-effects-on-gastric-carcinoma
#3
Lanying Ma, Mei Han, Zumureti Keyoumu, Hua Wang, Saifuding Keyoumu
BACKGROUND Tumorigenesis is a kind of pathology marked by infinite proliferation and restrained apoptosis compared with normal cells. The abnormal expression of some proto-oncogenes and apoptosis inhibition are essential for tumor growth, which has been confirmed by molecular biologic and immunologic studies. The hypofunction of the host immune system also drives the development and metastasis of malignant tumors. Bcl-2, which has a critical role in regulating apoptosis, is overexpressed in several cancers...
April 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28368239/apoptosis-of-pancreatic-%C3%AE-cells-in-type-1-diabetes
#4
REVIEW
Tatsuo Tomita
Type 1 diabetes mellitus (T1DM) results from autoimmune destruction of pancreatic β-cells after an asymptomatic period over years. Insulitis activates antigen presenting cells, which trigger activating CD4+ helper-T cells, releasing chemokines/cytokines. Cytokines activate CD8+ cytotoxic -T cells, which lead to β-cell destruction. Apoptosis pathway consists of extrinsic (receptor-mediated) and intrinsic (mitochondria-driven) pathway. Extrinsic pathway includes Fas pathway to CD4+-CD8+ interaction, whereas intrinsic pathway includes mitochondria-driven pathway at a balance between pro-apoptotic B-cell lymphoma (Bcl) 2 and Bcl-xL and anti-apoptotic Bad, Bid, and Bik proteins...
April 3, 2017: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28263097/transcriptional-and-epigenetic-regulation-of-follicular-t-helper-cells-and-their-role-in-autoimmunity
#5
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/28202459/il-4-cxcl12-loop-is-a-key-regulator-of-lymphoid-stroma-function-in-follicular-lymphoma
#6
Shubham Pandey, Frédéric Mourcin, Tony Marchand, Saba Nayar, Marion Guirriec, Céline Pangault, Céline Monvoisin, Patricia Amé-Thomas, Fabien Guilloton, Joelle Dulong, Mark Coles, Thierry Fest, Anja Mottok, Francesca Barone, Karin Tarte
Follicular lymphoma (FL) is the most frequent indolent lymphoma and is characterized by the accumulation of germinal center-derived malignant B cells engaged in a bidirectional crosstalk with their supportive microenvironment in invaded lymph nodes (LNs) and bone marrow (BM). T follicular helper (TFH) cells and infiltrating stromal cells have been shown to favor FL B-cell growth, but the mechanisms of their protumoral effect and how the LN/BM microenvironment is converted into a lymphoma-permissive cell niche remain poorly understood...
May 4, 2017: Blood
https://www.readbyqxmd.com/read/28194154/the-role-of-cd4-t-follicular-helper-cells-in-hiv-infection-from-the-germinal-center-to-the-periphery
#7
REVIEW
John Patrick Thornhill, Sarah Fidler, Paul Klenerman, John Frater, Chansavath Phetsouphanh
T follicular helper cells (TFh) are key components of the adaptive immune system; they are primarily found in germinal centers (GCs) where their interaction with B cells supports humoral immune responses and efficient antibody production. They are defined by the expression of CXC receptor 5, program death-1, ICOS, and secretion of IL-21. Their differentiation is regulated by B-cell lymphoma 6. The relationship and function of circulating TFh to bona fide TFh resident in the GC is much debated. HIV infection impacts the TFh response with evidence of aberrant TFh function observed in acute and chronic infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28134730/primary-cutaneous-follicular-helper-t-cell-lymphoma-in-a-patient-with-neurofibromatosis-type-1-case-report-and-review-of-the-literature
#8
REVIEW
Anastasia Shamsuyarova, Zaid Kamil, Jan Delabie, Nadya Al-Faraidy, Danny Ghazarian
Patients with neurofibromatosis type 1 (NF-1) have a well-known predisposition for certain types of malignancies, including lymphoproliferative disorders. Cutaneous T-cell lymphoma (CTCL) has been reported in patients with NF-1, although it is considered a rare entity in this subset of patients. Cutaneous follicular helper T-cell lymphoma (CTFHCL) is a recently emerged rare subtype of CTCL with peculiar clinical and histopathological features and represents a diagnostic and therapeutic challenge. Only a few cases of CTFHCL have been reported in the literature...
February 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28125450/clinicopathological-study-of-30-cases-of-peripheral-t-cell-lymphoma-with-hodgkin-and-reed-sternberg-like-b-cells-from-japan
#9
Ahmed E Eladl, Akira Satou, Ahmed Ali Elsayed, Yuka Suzuki, Seiichi Kato, Naoko Asano, Shigeo Nakamura
The presence of Hodgkin and Reed-Sternberg (HRS)-like B-cells in peripheral T-cell lymphoma (PTCL) is rare and its clinicopathological features still remain unclear. Here, we describe 30 cases of PTCL with HRS-like B-cells from Japan. Twenty-three cases (77%) presented evidence of follicular T-helper phenotype (TFH) derivation: 12 were angioimmunoblastic T-cell lymphoma and 11 PTCL with TFH phenotype (PTCL-TFH). The remaining seven cases were diagnosed as PTCL, not otherwise specified (PTCL-NOS). Epstein-Barr virus (EBV) reactivation was detected in 25 cases (83%), but HRS-like B-cells were EBER in only 20 cases (67%)...
April 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28096407/development-of-chronic-allergic-responses-by-dampening-bcl6-mediated-suppressor-activity-in-memory-t-helper-2-cells
#10
Takashi Ogasawara, Masahiko Hatano, Hisae Satake, Jun Ikari, Toshibumi Taniguchi, Nobuhide Tsuruoka, Haruko Watanabe-Takano, Lisa Fujimura, Akemi Sakamoto, Hirokuni Hirata, Kumiya Sugiyama, Yasutsugu Fukushima, Susumu Nakae, Kenji Matsumoto, Hirohisa Saito, Takeshi Fukuda, Kazuhiro Kurasawa, Koichiro Tatsumi, Takeshi Tokuhisa, Masafumi Arima
Mice deficient in the transcriptional repressor B-cell CLL/lymphoma 6 (Bcl6) exhibit similar T helper 2 (TH2) immune responses as patients with allergic diseases. However, the molecular mechanisms underlying Bcl6-directed regulation of TH2 cytokine genes remain unclear. We identified multiple Bcl6/STAT binding sites (BSs) in TH2 cytokine gene loci. We found that Bcl6 is modestly associated with the BSs, and it had no significant effect on cytokine production in newly differentiated TH2 cells. Contrarily, in memory TH2 (mTH2) cells derived from adaptively transferred TH2 effectors, Bcl6 outcompeted STAT5 for binding to TH2 cytokine gene loci, particularly Interleukin4 (Il4) loci, and attenuated GATA binding protein 3 (GATA3) binding to highly conserved intron enhancer regions in mTH2 cells...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27999289/characterization-of-the-microenvironment-of-nodular-lymphocyte-predominant-hodgkin-lymphoma
#11
Lydia Visser, Rui Wu, Bea Rutgers, Arjan Diepstra, Anke van den Berg
Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is characterized by a low percentage of neoplastic lymphocyte predominant (LP) cells in a background of lymphocytes. The goal of this study is to characterize the microenvironment in NLPHL. Ten NLPHL cases and seven reactive lymph nodes (RLN) were analyzed by flow cytometry for the main immune cells and multiple specific subpopulations. To discriminate between cells in or outside the tumor cell area, we used CD26. We observed significantly lower levels of CD20+ B-cells and CD56+ NK cells and higher levels of CD4+ T-cells in NLPHL in comparison to RLN...
December 16, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27987496/-detection-of-peripheral-follicular-helper-t-cells-in-rheumatoid-arthritis
#12
L M An, J Li, L L Ji, G T Li, Z L Zhang
OBJECTIVE: To detect cell frequency and surface markers of peripheral CD4(+)CXCR5+ follicular helper T (Tfh) cells and analyze the correlation between CD4(+)CXCR5(+)Tfh cells and rheumatoid arthritis (RA) disease activity. METHODS: Forty RA patients meeting the American College of Rheumatology classification criteria for RA and twenty healthy controls (HC) were included. The peripheral blood mononuclear cells and sera were collected. The expressions of CD4+CXCR5(+)Tfh cells (CXCR5, C-X-C chemokine receptor type 5) and inducible T cell costimulator (ICOS), programmed death 1 positive (PD-1), interleukin-21 receptor (IL-21R) and CD40 ligand (CD40L) positive on CD4(+)CXCR5(+)Tfh cells were analyzed by flow cytometry...
December 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27933753/mass-cytometry-of-follicular-lymphoma-tumors-reveals-intrinsic-heterogeneity-in-proteins-including-hla-dr-and-a-deficit-in-nonmalignant-plasmablast-and-germinal-center-b-cell-populations
#13
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 nonmalignant 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, nonmalignant 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...
January 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27933060/regulators-of-tfh-cell-differentiation
#14
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
#15
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...
April 2017: 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
#16
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...
January 1, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/27863842/development-of-t-follicular-helper-cells-and-their-role-in-disease-and-immune-system
#17
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...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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
#18
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
#19
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
#20
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
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