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https://www.readbyqxmd.com/read/28814601/il-15-complexes-induce-migration-of-resting-memory-cd8-t-cells-into-mucosal-tissues
#1
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...
August 16, 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
#2
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
#3
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
#4
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 3, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
Daruka Mahadevan, Shariful Islam, Wenqing Qi, Carla Morales, Laurence Cooke, Catherine Spier, Eric Weterings
Double Hit (DH) or Double Expressor (DE) diffuse large B-cell lymphoma (DLBCL) are aggressive Non-Hodgkin's Lymphomas (NHLs) with translocations and/or over-expressions of MYC and BCL-2, that 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 (AASCs), 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
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/28552541/primary-central-nervous-system-diffuse-large-b-cell-lymphoma-shows-an-activated-b-cell-like-phenotype-with-co-expression-of-c-myc-bcl-2-and-bcl-6
#15
Xiaomei Li, Ying Huang, Chengfeng Bi, Ji Yuan, Hong He, Hong Zhang, QiuBo Yu, Kai Fu, Dan Li
Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma, whose main prognostic factor is closely related to germinal center B-cell-like subtype (GCB- DLBCL) or activated B-cell-like type (non-GCB-DLBCL). The most common type of primary central nervous system lymphoma is diffuse large B-cell type with poor prognosis and the reason is unclear. This study aims to stratify primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) according to the cell-of-origin (COO) and to investigate the multiple proteins expression of C-MYC, BCL-6, BCL-2, TP53, further to elucidate the reason why primary central nervous system diffuse large B-cell lymphoma possesses a poor clinical outcome as well...
June 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28549475/kimura-s-disease-affecting-the-axillary-lymph-nodes-a-case-report
#16
Kenji Kuroda, Shinichiro Kashiwagi, Hitoshi Teraoka, Haruhito Kinoshita, Mikio Nanbara, Eiji Noda, Takaaki Chikugo, Kosei Hirakawa, Masaichi Ohira
BACKGROUND: Kimura's disease (KD; eosinophilic granuloma of soft tissue) is an inflammatory granulomatous disorder of unknown cause with eosinophilic infiltration that occurs mainly in soft tissue. KD occurs mainly in the head and neck, but development in the axillary region is very rare. CASE PRESENTATION: A 74-year-old Japanese woman was evaluated for a mass that she noted in the left axillary region. On physical examination, there was a palpable, thumb-sized, hard, elastic, freely movable mass in the left axilla...
May 26, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28486965/site-specific-gene-expression-patterns-in-oral-cancer
#17
Gesche Frohwitter, Horst Buerger, Eberhard Korsching, Paul J van Diest, Johannes Kleinheinz, Thomas Fillies
BACKGROUND: Squamous cell carcinomas (SCCs) are the most prevalent malignant tumours within the head and neck. Evidence exists that distinct genes are differentially regulated in SCCs of the oral cavity compared to other head and neck regions. Given this background, the aim of this study was to investigate whether such tumour site-specific gene expression can also be observed in different localizations within the oral cavity. METHODS: Using tissue microarrays (TMAs), we investigated 76 SCCs of the floor of the mouth, 49 SCCs of the tongue and 68 SCCs of other anatomic regions within the oral cavity...
May 10, 2017: Head & Face Medicine
https://www.readbyqxmd.com/read/28485382/single-cell-profiling-of-lineage-determining-transcription-factors-in-antigen-specific-cd4-t-cells-reveals-unexpected-complexity-in-recall-responses-during-immune-reconstitution
#18
Chansavath Phetsouphanh, Yin Xu, Mee Ling Munier, John J Zaunders, Anthony D Kelleher
Recent studies of protein and gene expression at the single-cell level have revealed that the memory T-cell compartment is more heterogeneous than previously acknowledged. Identifying different T helper subsets involved in memory responses at the single-cell level is thus necessary to understand the level of heterogeneity within this population. Antigen-specific CD4(+) T cells were measured using the CD25/OX40 assay together with a qualitative multiplex single-cell RT-PCR assay. Transcription profiles and subset proportions within the antigen-specific CD4(+) T-cell population were dissected...
August 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28476134/overexpression-of-rkip-and-its-cross-talk-with-several-regulatory-gene-products-in-multiple-myeloma
#19
REVIEW
Anna Shvartsur, Kevin B Givechian, Hermes Garban, Benjamin Bonavida
Multiple myeloma (MM) is a clonal plasma-cell neoplastic disorder arising from an indolent premalignant disease known as monoclonal gammopathy of undetermined significance (MGUS). MM is a biologically complex heterogeneous disease reflected by its variable clinical responses of patients receiving the same treatment. Therefore, a molecular identification of stage-specific biomarkers will support a more individualized precise diagnostic/prognostic approach, an effective therapeutic regime, and will assist in the identification of novel therapeutic molecular targets...
May 5, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28468797/selective-inhibition-of-nuclear-export-with-selinexor-in-patients-with-non-hodgkin-lymphoma
#20
MULTICENTER STUDY
John Kuruvilla, Michael Savona, Rachid Baz, Paul Morten Mau-Sorensen, Nashat Gabrail, Ramiro Garzon, Richard Stone, Michael Wang, Lynn Savoie, Peter Martin, Ian Flinn, Meagan Jacoby, Thaddeus J Unger, Jean-Richard Saint-Martin, Tami Rashal, Sharon Friedlander, Robert Carlson, Michael Kauffman, Sharon Shacham, Martin Gutierrez
Patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) have a poor prognosis and limited treatment options. We evaluated selinexor, an orally bioavailable, first-in-class inhibitor of the nuclear export protein XPO1, in this phase 1 trial to assess safety and determine a recommended phase 2 dose (RP2D). Seventy-nine patients with various NHL histologies, including diffuse large B-cell lymphoma, Richter's transformation, mantle cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia, were enrolled...
June 15, 2017: Blood
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