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https://www.readbyqxmd.com/read/28930662/the-kinase-mtorc1-promotes-the-generation-and-suppressive-function-of-follicular-regulatory-t-cells
#1
Lifan Xu, Qizhao Huang, Haoqiang Wang, Yaxing Hao, Qiang Bai, Jianjun Hu, Yiding Li, Pengcheng Wang, Xiangyu Chen, Ran He, Bingshou Li, Xia Yang, Tingting Zhao, Yanyan Zhang, Yifei Wang, Juanjuan Ou, Houjie Liang, Yuzhang Wu, Xinyuan Zhou, Lilin Ye
Follicular regulatory T (Tfr) cells differentiate from conventional regulatory T (Treg) cells and suppress excessive germinal center (GC) responses by acting on both GC B cells and T follicular helper (Tfh) cells. Here, we examined the impact of mTOR, a serine/threonine protein kinase that senses and integrates diverse environmental cues, on the differentiation and functional competency of Tfr cells in response to protein immunization or viral infection. By genetically deleting Rptor or Rictor, essential components for mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), respectively, we found that mTORC1 but not mTORC2 is essential for Tfr differentiation...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28901193/erk-and-p38-upregulation-versus-bcl-6-downregulation-in-rat-kidney-epithelial-cells-exposed-to-prolonged-hypoxia
#2
Fengbao Luo, Jian Shi, Qianqian Shi, Xiaozhou He, Ying Xia
Hypoxia is a common cause of kidney injury and a major issue in kidney transplantation. Mitogen-activated protein kinases (MAPKs) are involved in the cellular response to hypoxia, but the precise roles of MAPKs in renal cell reactions to hypoxic stress are not well known yet. This work was conducted to investigate the regulation of extracellular signal-regulated kinase-1 and -2 (ERK1/2) and p38 and their signaling-relevant molecules in kidney epithelial cells exposed to prolonged hypoxia. Rat kidney epithelial cells Normal Rat Kidney (NRK)-52E were exposed to hypoxic conditions (1% O2) for 24 to 72 h...
August 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28892471/dynamic-regulation-of-t-follicular-regulatory-cell-responses-by-interleukin-2-during-influenza-infection
#3
Davide Botta, Michael J Fuller, Tatiana T Marquez-Lago, Holly Bachus, John E Bradley, Amy S Weinmann, Allan J Zajac, Troy D Randall, Frances E Lund, Beatriz León, André Ballesteros-Tato
Interleukin 2 (IL-2) promotes Foxp3(+) regulatory T (Treg) cell responses, but inhibits T follicular helper (TFH) cell development. However, it is not clear how IL-2 affects T follicular regulatory (TFR) cells, a cell type with properties of both Treg and TFH cells. Using an influenza infection model, we found that high IL-2 concentrations at the peak of the infection prevented TFR cell development by a Blimp-1-dependent mechanism. However, once the immune response resolved, some Treg cells downregulated CD25, upregulated Bcl-6 and differentiated into TFR cells, which then migrated into the B cell follicles to prevent the expansion of self-reactive B cell clones...
November 2017: Nature Immunology
https://www.readbyqxmd.com/read/28881619/mrna-in-exosomas-as-a-liquid-biopsy-in-non-hodgkin-lymphoma-a-multicentric-study-by-the-spanish-lymphoma-oncology-group
#4
Mariano Provencio, Marta Rodríguez, Blanca Cantos, Pilar Sabín, Cristina Quero, Francisco R García-Arroyo, Antonio Rueda, Constanza Maximiano, Delvys Rodríguez-Abreu, Antonio Sánchez, Javier Silva, Vanesa García
PURPOSE: To determine the feasibility of mRNAs (C-MYC, BCL-XL, BCL-6, NF-κβ, PTEN and AKT) in exosomes of plasma as a liquid biopsy method for monitoring and prognostic evolution in B-cell lymphomas. PATIENTS AND METHODS: Exosomes were isolated from 98 patients with B-cell Lymphoma and 68 healthy controls. mRNAs were analyzed by quantitative PCR. An additional 31 post-treatment samples were also studied. RESULTS: In the general and follicular lymphoma series, the presence of AKT mRNA was associated with poor response to rituximab-based treatment...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881401/generation-of-t-follicular-helper-cells-in-vitro-requirement-for-bcr-cross-linking-and-cognate-b-and-t-cell-interaction
#5
Anne Kolenbrander, Bastian Grewe, David Nemazee, Klaus Überla, Vladimir Temchura
The minimal requirements for in vitro modeling of the natural CD4(+) T-cell differentiation into T follicular helper (TFH) cells are still under investigation. We co-cultured wild type and TCR-transgenic CD4(+) T-cells from naïve mice with dendritic cells and BCR-transgenic B-cells in the presence of HIV-derived virus-like particles containing matched B- and T-cell epitopes. This co-culturing induced co-expression of TFH-master regulator transcription factor BCL-6 and CXCR5 in up to 10% of the wild type and up to 40% of the TCR-transgenic CD4(+) T-cells...
September 7, 2017: Immunology
https://www.readbyqxmd.com/read/28862126/diffuse-large-b-cell-lymphoma-in-a-male-breast-a-rare-case-report
#6
Adelina Birceanu Corobea, Adrian Dumitru, Maria Sajin, Radu Poenaru, Ana Puşcaşu, Dragoş Chirita, Anca Evsei
Primary breast diffuse large B cell lymphoma (PBL) in male patients represents a rare clinical phenomenon and can imitate a breast carcinoma in its clinical presentation, so, therefore, the initial treatment for most patients remains surgery. Prompt diagnosis associating subsequent treatment combining chemotherapy and radiotherapy are of the utmost importance. We herein report a 56 years old male patient diagnosed with diffuse large B cell lymphoma, after clinically presenting with a visible tumor in the left breast and showing no axillary lymphadenopathy...
July 2017: Chirurgia
https://www.readbyqxmd.com/read/28814601/il-15-complexes-induce-migration-of-resting-memory-cd8-t-cells-into-mucosal-tissues
#7
Ryan T Sowell, Josef W Goldufsky, Magdalena Rogozinska, Zurisaday Quiles, Yanxia Cao, Eliseo F Castillo, Alison Finnegan, Amanda L Marzo
IL-15 is an essential cytokine known to promote T cell survival and activate the effector function of memory phenotype CD8 T cells. Blocking IL-15 signals also significantly impacts tissue-specific effector and memory CD8 T cell formation. In this study, we demonstrate that IL-15 influences the generation of memory CD8 T cells by first promoting their accumulation into mucosal tissues and second by sustaining expression of Bcl-6 and T-bet. We show that the mechanism for this recruitment is largely dependent on mammalian target of rapamycin and its subsequent inactivation of FoxO1...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28810929/the-impact-of-age-and-gut-microbiota-on-th17-and-tfh-cells-in-k-bxn-autoimmune-arthritis
#8
Fei Teng, Krysta M Felix, C Pierce Bradley, Debdut Naskar, Heqing Ma, Walid A Raslan, Hsin-Jung Joyce Wu
BACKGROUND: Age is an important risk factor for rheumatoid arthritis (RA), which often develops in middle age. However, how age-associated changes in immunity impact RA is poorly understood. Gut microbiota are known to be involved in the pathogenesis of RA, but the effects of microbiota in older subjects remain mostly unknown. METHODS: We used segmented filamentous bacteria (SFB), a gut commensal species with immunomodulatory effects, and K/BxN mice, a T cell receptor (TCR) transgenic model, to study the effect of age and microbiota on autoimmune arthritis...
August 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28776551/advances-in-pathobiology-of-primary-central-nervous-system-lymphoma
#9
REVIEW
Xue-Liang Yang, Yuan-Bo Liu
OBJECTIVE: Primary central nervous system lymphoma (PCNSL) is a specific type of non-Hodgkin lymphoma with poor prognosis. The rare incidence of this disease and difficulty to obtain sufficient tissue material impede deep research into PCNSL. However, application of modern molecular techniques makes it possible to find biological characteristics exclusive to PCNSL. Therefore, we systematically reviewed the latest research progress on biological characteristics and pathogenesis of PCNSL...
August 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28771100/rare-transformation-to-double-hit-lymphoma-in-waldenstrom-s-macroglobulinemia
#10
Onyemaechi N Okolo, Ariel C Johnson, Seongseok Yun, Stacy J Arnold, Faiz Anwer
Waldenström macroglobulinemia (WM) is a lymphoproliferative lymphoma that is characterized by monoclonal immunoglobulin M (IgM) protein and bone marrow infiltration. Its incidence is rare and rarer still is its ability to transform to a B-cell lymphoma, particularly the aggressive diffuse large B-cell lymphoma, which bodes a poor prognosis. When transformation includes mutations of MYC, BCL-2 and/or BCL-6, it is known as a 'double hit' or 'triple hit' lymphoma respectively. This paper presents a rare case of WM with mutations positive for MYC and BCL2, making it a case of double hit B-cell lymphoplasmacytic lymphoma with plasmatic differentiation without morphological transformation to aggressive histology like DLBCL...
August 2017: Immunotherapy
https://www.readbyqxmd.com/read/28743581/caspase-1-inhibitor-regulates-humoral-responses-in-experimental-autoimmune-myasthenia-gravis-via-il-6-dependent-inhibiton-of-stat3
#11
Cong-Cong Wang, Min Zhang, Heng Li, Xiao-Li Li, Long-Tao Yue, Peng Zhang, Ru-Tao Liu, Hui Chen, Yan-Bin Li, Rui-Sheng Duan
We have previously demonstrated that Cysteinyl aspartate-specific proteinase-1 (caspase-1) inhibitor ameliorates experimental autoimmune myasthenia gravis (EAMG) by inhibited cellular immune response, via suppressing DC IL-1 β, CD4(+) T and γdT cells IL-17 pathways. In this study, we investigated the effect of caspase-1 inhibitor on humoral immune response of EAMG and further explore the underlying mechanisms. An animal model of MG was induced by region 97-116 of the rat AChR α subunit (R97-116 peptide) in Lewis rats...
July 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28728856/achaete-scute-complex-homologue-2-accelerates-the-development-of-sj%C3%A3-gren-s-syndrome-like-disease-in-the-nod-shiltj-mouse
#12
Sung-Min Kim, Jeong-Eun Kwon, Jin-Sil Park, Hyeon-Beom Seo, Kyung-Ah Jung, Young-Mee Moon, Jennifer Lee, Seung-Ki Kwok, Mi-La Cho, Sung-Hwan Park
Achaete-scute complex homologue 2 (Ascl2) has been reported to induce the differentiation and activation of follicular helper T (TFH) cells, which are essential for development of Sjögren's syndrome (SS). This study examined whether Ascl2 plays a role in the development of SS. NOD/ShiLtJ mice were injected with an Ascl2-overexpression vector, and the infiltration of lymphocytes into salivary and lacrimal glands was assessed. The expression of inflammatory cytokines and chemoattractants for T or B cells was measured...
July 17, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28689040/unsupervised-learning-techniques-reveal-heterogeneity-in-memory-cd8-t-cell-differentiation-following-acute-chronic-and-latent-viral-infections
#13
Mingyong Liu, Erik S Barton, Ryan N Jennings, Darby G Oldenburg, Juliann M Whirry, Douglas W White, Jason M Grayson
CD8(+) T lymphocytes are critical for the control of gammaherpesvirus latency. To determine how memory CD8(+) T cells generated during latency differ from those primed during acute or chronic viral infection, we adoptively transferred naive P14 CD8(+) T cells into uninfected recipients, and examined surface proteins, cytokines and transcription factors following infection with the Armstrong (acute) or Clone 13 (chronic) strains of lymphocytic choriomeningitis virus (LCMV), or murine gammaherpesvirus 68 (MHV68) expressing the LCMV epitope D(b)GP33-41...
September 2017: Virology
https://www.readbyqxmd.com/read/28642849/aim2-co-immunization-with-vp1-is-associated-with-increased-memory-cd8-t-cells-and-mounts-long-lasting-protection-against-coxsackievirus-b3-challenge
#14
Liang Yin, Dafei Chai, Yan Yue, Chunsheng Dong, Sidong Xiong
The recurrent Coxsackievirus B3 (CVB3) infection is the most important cause of intractable myocarditis which often leads to chronic myocarditis and even dilated cardiomyopathy. Therefore, enhanced DNA vaccines capable of memory CD8 T cells are essential for long-lasting immunological protection against CVB3 infection. In this study, absent in melanoma 2 (AIM2) was used as an adjuvant to enhance the induction of memory CD8 T cells elicited by VP1 (viral capsid protein 1) vaccine. Mice were intramuscularly injected with 50 μg AIM2 plasmid and equal amount of VP1 plasmid (pAIM2/pVP1) vaccine 4 times at 2 week-intervals...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28620653/successive-annual-influenza-vaccination-induces-a-recurrent-oligoclonotypic-memory-response-in-circulating-t-follicular-helper-cells
#15
Ramin Sedaghat Herati, Alexander Muselman, Laura Vella, Bertram Bengsch, Kaela Parkhouse, Daniel Del Alcazar, Jonathan Kotzin, Susan A Doyle, Pablo Tebas, Scott E Hensley, Laura F Su, Kenneth E Schmader, E John Wherry
T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population of CD4 T cells, termed cTfh, have similarity to lymphoid Tfh, can provide B cell help, and responded to influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner and whether they form long-lasting memory. Here, we identified a cTfh population that expressed multiple T cell activation markers and could be readily identified by coexpression of ICOS and CD38...
February 2017: Science Immunology
https://www.readbyqxmd.com/read/28615297/disruption-of-aneuploidy-and-senescence-induced-by-aurora-inhibition-promotes-intrinsic-apoptosis-in-double-hit-or-double-expressor-diffuse-large-b-cell-lymphomas
#16
Shariful Islam, Wenqing Qi, Carla Morales, Laurence Cooke, Catherine Spier, Eric Weterings, Daruka Mahadevan
Double hit (DH) or double expressor (DE) diffuse large B-cell lymphomas (DLBCL) are aggressive non-Hodgkin's lymphomas (NHL) with translocations and/or overexpressions of MYC and BCL-2, which are difficult to treat. Aurora kinase (AK) inhibition with alisertib in DH/DE-DLBCL induces cell death in ∼30%, while ∼70% are aneuploid and senescent cells (AASC), a mitotic escape mechanism contributing to drug resistance. These AASCs elaborated a high metabolic rate by increased AKT/mTOR and ERK/MAPK activity via BTK signaling through the chronic active B-cell receptor (BCR) pathway...
June 14, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28600333/how-i-treat-double-hit-lymphoma
#17
REVIEW
Jonathan W Friedberg
The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6. These lymphomas, which occur in <10% of cases of diffuse large B-cell lymphoma, have been referred to as double-hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity...
August 3, 2017: Blood
https://www.readbyqxmd.com/read/28599246/ablation-of-il-17-expression-moderates-experimental-autoimmune-myasthenia-gravis-disease-severity
#18
Gabriela Aguilo-Seara, Yanchen Xie, Jarrod Sheehan, Linda L Kusner, Henry J Kaminski
An array of cytokines influences the pathogenesis of early onset myasthenia gravis (MG) and its animal model, experimental autoimmune myasthenia gravis (EAMG). Patients with MG, in particular those with more severe weakness, have elevations of the pro-inflammatory cytokine IL-17 in the blood. We assessed the role of IL-17A in autoimmunity by inducing EAMG in mice with knockout of IL-17 and found a reduction of EAMG severity, but not a complete ablation of disease. The IL-17(ko) mice had no evidence of weakness, low levels of acetylcholine receptor antibodies, and retention of acetylcholine receptor at the neuromuscular junction...
August 2017: Cytokine
https://www.readbyqxmd.com/read/28591984/-clinicopathologic-features-and-expression-of-oct4-protein-in-testicular-diffuse-large-b-cell-lymphoma
#19
Y P Chen, W F Zhu, L F Chen, J P Lu, T M He, W D Fu, C W Xu, G Chen
Objective: To evaluate the expression of OCT4 and SALL4 in testicular diffuse large B-cell lymphoma (DLBCL), and the utility of an immunohistochemical (IHC) panel of OCT4, SALL4 and CD20 in the differential diagnosis of DLBCL and GCT of the testis. Methods: Eighteen cases of testicular DLBCL were selected.IHC method was used to detect the protein expression of CD20, CD3, CD5, CD10, bcl-6, MUM1, Ki-67, bcl-2, c-MYC, OCT4 and SALL4. Results: Among the 18 cases, CD20 and PAX5 were strongly and diffusely expressed in all cases, while CD21, CD3, cyclinD1, SALL4, CD117 and PLAP were all negative...
June 8, 2017: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
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
#20
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
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