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https://www.readbyqxmd.com/read/29786142/the-bone-marrow-is-not-only-a-primary-lymphoid-organ-the-critical-role-for-t-lymphocyte-migration-and-housing-of-long-term-memory-plasma-cells
#1
REVIEW
Reinhard Pabst
In immunology and anatomy textbooks the bone marrow is described as a typical "primary lymphoid organ" producing lymphoid cells independent of antigens. The hematopoietic bone marrow is largely age-dependent organ with great anatomical and functional differences among various species. There are estimates that about 12 % of all lymphoid cells in the human body are found in the bone marrow at any given time (2 % in the peripheral blood). Enormous numbers of T lymphocytes migrate to the bone marrow and partly return later to the blood...
May 22, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29784854/molecular-subtype-specific-immunocompetent-models-of-high-grade-urothelial-carcinoma-reveal-differential-neoantigen-expression-and-response-to-immunotherapy
#2
Ryoichi Saito, Christof C Smith, Takanobu Utsumi, Lisa M Bixby, Jordan Kardos, Sara E Wobker, Kyle G Stewart, Shengjie Chai, Ujjawal Manocha, Kevin Matthew Byrd, Jeffrey S Damrauer, Scott E Williams, Benjamin G Vincent, William Y Kim
High-grade urothelial cancer contains intrinsic molecular subtypes that exhibit differences in underlying tumor biology and can be divided into luminal-like and basal-like subtypes. We describe here the first subtype-specific murine models of bladder cancer and show that Upk3a-CreERT2; Trp53L/L; PtenL/L; Rosa26LSL-Luc (UPPL: luminal-like) and BBN (basal-like) tumors are more faithful to human bladder cancer than the widely-used MB49 cells. Following engraftment into immunocompetent C57BL/6 mice, BBN tumors were more responsive to PD-1 inhibition than UPPL tumors...
May 21, 2018: Cancer Research
https://www.readbyqxmd.com/read/29783767/direct-detection-of-t-and-b-memory-lymphocytes-by-immunospot%C3%A2-assays-reveals-hcmv-exposure-that-serum-antibodies-fail-to-identify
#3
Fredrik Terlutter, Richard Caspell, Tobias M Nowacki, Alexander Lehmann, Ruliang Li, Ting Zhang, Anna Przybyla, Stefanie Kuerten, Paul V Lehmann
It is essential to identify donors who have not been infected with human cytomegalovirus (HCMV) in order to avoid transmission of HCMV to recipients of blood transfusions or organ transplants. In the present study, we tested the reliability of seronegativity as an indicator for the lack of HCMV exposure in healthy human blood donors. Eighty-two HCMV seronegative individuals were identified, and their peripheral blood mononuclear cells (PBMC) were tested in ImmunoSpot® assays for the presence of HCMV-specific T- and B-memory lymphocytes...
May 19, 2018: Cells
https://www.readbyqxmd.com/read/29781885/improved-cognitive-performance-and-reduced-monocyte-activation-in-virally-suppressed-chronic-hiv-following-dual-ccr2-and-ccr5-antagonism
#4
Michelle L D'Antoni, Robert H Paul, Brooks I Mitchell, Lindsay Kohorn, Laurent Fischer, Eric Lefebvre, Star Seyedkazemi, Beau K Nakamoto, Maegen Walker, Kalpana J Kallianpur, Debra Ogata-Arakaki, Lishomwa C Ndhlovu, Cecilia Shikuma
OBJECTIVE: To evaluate changes in neuropsychological (NP) performance and in plasma and cell surface markers of peripheral monocyte activation/migration following treatment with cenicriviroc (CVC), a dual C-C chemokine receptor type 2 (CCR2) and type 5 (CCR5) antagonist, in treatment-experienced, HIV-infected individuals. SETTING: Single-arm, 24-week, open-label clinical trial. METHODS: HIV-infected individuals on antiretroviral therapy (ART) >1 year with plasma HIV RNA <50 copies/ml and below-normal cognitive performance [defined as age, gender and education-adjusted NP performance (NPZ) <-0...
May 16, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29780389/deep-surveying-of-the-transcriptional-and-alternative-splicing-signatures-for-decidual-cd8-t-cells-at-the-first-trimester-of-human-healthy-pregnancy
#5
Weihong Zeng, Xinmei Liu, Zhicui Liu, Ying Zheng, Tiantian Yu, Shaliu Fu, Xiao Li, Jing Zhang, Siming Zhang, Xiaoling Ma, Xiao-Rui Liu, Xiaoli Qin, Asma Khanniche, Yan Zhang, Fuju Tian, Yi Lin
Decidual CD8+ (dCD8) T cells have been proposed to play important roles in immune protection against the invading pathogens and in tolerance toward the growing semi-allogeneic fetus during early pregnancy. However, their phenotypic and functional characteristics remain poorly defined. Here, we performed the first analysis of the transcriptional and alternative splicing (AS) signatures for human first-trimester dCD8 T cells using high-throughput mRNA sequencing. Our data revealed that dCD8 T cells have distinct transcriptional and AS landscapes when compared with their autologous peripheral blood CD8+ (pCD8) T counterparts...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29770133/peripheral-blood-stem-cell-mobilization-in-healthy-donors-by-granulocyte-colony-stimulating-factor-causes-preferential-mobilization-of-lymphocyte-subsets
#6
Guro Kristin Melve, Elisabeth Ersvaer, Geir Egil Eide, Einar K Kristoffersen, Øystein Bruserud
Background: Allogeneic hematopoietic stem cell transplantation is associated with a high risk of immune-mediated post-transplant complications. Graft depletion of immunocompetent cell subsets is regarded as a possible strategy to reduce this risk without reducing antileukemic immune reactivity. Study design and methods: We investigated the effect of hematopoietic stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) on peripheral blood and stem cell graft levels of various T, B, and NK cell subsets in healthy donors...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29769201/in-vitro-priming-of-adoptively-transferred-t-cells-with-a-ror%C3%AE-agonist-confers-durable-memory-and-stemness-in-vivo
#7
Xiao Hu, Kinga Majchrzak, Xikui Liu, Megan M Wyatt, Chauncey Spooner, Jacques Moisan, Weiping Zou, Laura L Carter, Chrystal M Paulos
Adoptive T cell transfer therapy is an FDA-approved treatment for leukemia that relies on the ex vivo expansion and re-infusion of a patient's immune cells, which can be engineered with a chimeric antigen receptor (CAR) for more efficient tumor recognition. Type 17 T cells, controlled transcriptionally by RORγ, have been reported to mediate potent anti-tumor effects superior to those observed with conventionally expanded T cells. Here we demonstrate that addition of a synthetic, small molecule RORγ agonist during ex vivo expansion potentiates the anti-tumor activity of human Th17 and Tc17 cells redirected with a CAR...
May 16, 2018: Cancer Research
https://www.readbyqxmd.com/read/29769184/explaining-resistance-to-car-t-cells
#8
(no author information available yet)
A new study reveals several attributes of T cells from patients with chronic lymphocytic leukemia who respond to CAR T-cell therapy. The patients' T cells show increased expression of memory-related genes and high activity of STAT3, which promotes memory cell differentiation. The researchers also found that patients who underwent complete remission have certain CD8+ T cells.
May 16, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29755666/impact-of-lenalidomide-maintenance-on-the-immune-environment-of-multiple-myeloma-patients-with-low-tumor-burden-after-autologous-stem-cell-transplantation
#9
Karel Fostier, Jo Caers, Nathalie Meuleman, Katrijn Broos, Jurgen Corthals, Kris Thielemans, Rik Schots, Brenda De Keersmaecker
Lenalidomide is a potent anti-myeloma drug with immunomodulatory properties. It is increasingly used in a low-dose maintenance setting to prolong remission duration after standard treatment. Data on the in vivo effects of lenalidomide are scarce and sometimes different from the well-described in vitro effects. We therefore evaluated the numerical, phenotypical and functional impact of lenalidomide maintenance on several immune cell types in a cohort of seventeen homogeneously treated myeloma patients achieving a low residual myeloma burden after a bortezomib based-induction followed by autologous stem cell transplantation...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29755647/autologous-tumor-cells-bacillus-calmette-gu%C3%A3-rin-formalin-based-novel-breast-cancer-vaccine-induces-an-immune-antitumor-response
#10
María José Godoy-Calderón, Víctor Salazar, Eglys González-Marcano, Ana Federica Convit
Autologous cancer cell vaccines represent a multivalent patient-specific treatment. Studies have demonstrated that these immunotherapies should be combined with immunomodulators to improve results. We tested in breast cancer the antitumor effects of a 200 µg autologous tumor cells homogenate combined with 0.0625 mg of bacillus Calmette-Guérin (BCG), and 0.02% formalin. We used a 4T1 murine model of BALB/c receiving four weekly injections of either this vaccine or control treatments. The control treatments were either Phosphate Buffer Saline, BCG treated with formalin, or the tumor cells homogenate plus BCG alone...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752423/strong-homeostatic-tcr-signals-induce-formation-of-self-tolerant-virtual-memory-cd8-t-cells
#11
Ales Drobek, Alena Moudra, Daniel Mueller, Martina Huranova, Veronika Horkova, Michaela Pribikova, Robert Ivanek, Susanne Oberle, Dietmar Zehn, Kathy D McCoy, Peter Draber, Ondrej Stepanek
Virtual memory T cells are foreign antigen-inexperienced T cells that have acquired memory-like phenotype and constitute 10-20% of all peripheral CD8+ T cells in mice. Their origin, biological roles, and relationship to naïve and foreign antigen-experienced memory T cells are incompletely understood. By analyzing T-cell receptor repertoires and using retrogenic monoclonal T-cell populations, we demonstrate that the virtual memory T-cell formation is a so far unappreciated cell fate decision checkpoint. We describe two molecular mechanisms driving the formation of virtual memory T cells...
May 11, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29749428/accumulation-of-cd69-tissue%C3%A2-resident-memory-t-cells-in-the-nasal-polyps-of-patients-with-chronic-rhinosinusitis
#12
Pascal Ickrath, Norbert Kleinsasser, Xin Ding, Christian Ginzkey, Niklas Beyersdorf, Rudolf Hagen, Thomas Kerkau, Stephan Hackenberg
In patients with chronic rhinosinusitis with nasal polyps (CRSwNP), a relative accumulation of cluster of differentiation (CD)8+ T cells over CD4+ T cells occurs in nasal polyps compared with the peripheral blood. Nasal CD8+ T cells and CD4+ T cells predominantly present an effector memory phenotype. Immunological studies have reported that memory T cells recirculate from the tissues to the peripheral blood and a high percentage of these T cells persist within the tissue. The aim of the present study was to characterize CD69+ sphingosine‑1‑phosphate receptor 1 (S1PR1)‑ tissue resident memory T cells (Trm) in the polyps of patients with CRSwNP...
May 2, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29746376/neruodevelopmental-outcomes-in-pre-school-children-living-with-hiv-1-subtypes-a-and-d-in-uganda
#13
Horacio Ruiseñor-Escudero, Alla Sikorskii, Itziar Familiar-Lopez, Deborah Persaud, Carrie Ziemniak, Noeline Nakasujja, Robert Opoka, Michael Boivin
BACKGROUND: HIV is a neuropathogenic virus that may result in detrimental neurodevelopmental (ND) outcomes early in life. This is the first study to evaluate the effect of HIV-1 subtype on neurodevelopment of Ugandan pre-school children. METHODS: Neurodevelopment of 87 HIV-1 infected and 221 HIV exposed uninfected (HEU) Ugandan children aged 1.8 to 4.9 years was assessed using four scales of the Mullen Scales of Early Learning (MSEL), two scales of the Color Object Association Test (COAT), and one score of the Early Childhood Vigilance Test (ECVT)...
May 9, 2018: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29745988/differential-requirements-for-irf4-in-the-clonal-expansion-and-homeostatic-proliferation-of-naive-and-memory-murine-cd8-t-cells
#14
Mana Miyakoda, Kiri Honma, Daisuke Kimura, Masoud Akbari, Kazumi Kimura, Toshifumi Matsuyama, Katsuyuki Yui
Interferon regulatory factor 4 (IRF4) has critical roles in immune cell differentiation and function and is indispensable for clonal expansion and effector function in T cells. Here, we demonstrate that the AKT pathway is impaired in murine CD8+ T cells lacking IRF4. The expression of phosphatase and tensin homolog (PTEN), a negative regulator of the AKT pathway, was elevated in Irf4-/- CD8+ T cells. Inhibition of PTEN partially rescued downstream events, suggesting that PTEN constitutes a checkpoint in the IRF4-mediated regulation of cell signaling...
May 10, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29743478/transcriptome-analysis-in-whole-blood-reveals-increased-microbial-diversity-in-schizophrenia
#15
Loes M Olde Loohuis, Serghei Mangul, Anil P S Ori, Guillaume Jospin, David Koslicki, Harry Taegyun Yang, Timothy Wu, Marco P Boks, Catherine Lomen-Hoerth, Martina Wiedau-Pazos, Rita M Cantor, Willem M de Vos, René S Kahn, Eleazar Eskin, Roel A Ophoff
The role of the human microbiome in health and disease is increasingly appreciated. We studied the composition of microbial communities present in blood across 192 individuals, including healthy controls and patients with three disorders affecting the brain: schizophrenia, amyotrophic lateral sclerosis, and bipolar disorder. By using high-quality unmapped RNA sequencing reads as candidate microbial reads, we performed profiling of microbial transcripts detected in whole blood. We were able to detect a wide range of bacterial and archaeal phyla in blood...
May 10, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29742730/il-35-producing-b-cells-in-gastric-cancer-patients
#16
Ke Wang, Jianming Liu, Jiansheng Li
A significant characteristic of advanced gastric cancer (GC) is immune suppression, which can promote the progression of GC. Interleukin 35 (IL-35) is an immune-suppressing cytokine, and it is generally recognized that this cytokine is secreted by regulatory T (Treg) cells. Recently, studies have found that IL-35 can also be produced by B cells in mice. However, scientific studies reporting that IL-35 is secreted by B cells in humans, specifically in cancer patients, are very rare.Blood samples were collected from 30 healthy controls (HCs) and 50 untreated GC patients, and IL-35-producing B cells in the peripheral blood were investigated...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29740910/gene-expression-profiles-of-cd4-cd8-double-positive-t-cells-in-porcine-peripheral-blood
#17
Mie Okutani, Takamitsu Tsukahara, Yoshihiro Kato, Kikuto Fukuta, Ryo Inoue
A characteristic subset of T cells, known as double positive T cells (DPTC) and expressing both cluster of differentiation 4 (CD4) and CD8, is observed in porcine peripheral blood. Previous studies suggested that DPTC might be memory cells. However, detailed phenotypes and functions of DPTC are yet to be fully elucidated and thus, the relatedness of DPTC with memory phenotypes remains unclear. In this study, DPTC gene expression profiles in peripheral blood were analyzed by DNA microarray in Experiment 1 and compared with those of CD4 single positive T cells (4SPTC) and CD8 single positive T cells (8SPTC)...
May 8, 2018: Animal Science Journal, Nihon Chikusan Gakkaihō
https://www.readbyqxmd.com/read/29738081/prame-peptide-specific-cd8-t-cells-represent-the-predominant-response-against-leukemia-associated-antigens-laas-in-healthy-individuals
#18
Sarah Matko, Julia Manderla, Maria Bonsack, Marc Schmitz, Martin Bornhauser, Torsten Tonn, Marcus Odendahl
Antigen-specific T cells isolated from healthy individuals (HIs) have shown great therapeutic potential upon adoptive transfer for the treatment of viremia in immunosuppressed patients. The lack of comprehensive data on the prevalence and characteristics of leukemia associated antigen (LAA)-specific T cells in HIs still limits such an approach for tumor therapy. Therefore, we have investigated T cell responses against prominent candidates comprising WT1, PRAME, Survivin, NY-ESO and p53 by screening PBMCs from HIs using intracellular IFN-γ staining following provocation with LAA peptide mixes...
May 8, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29735644/invariant-nkt-cells-and-control-of-the-thymus-medulla
#19
REVIEW
Andrea J White, Beth Lucas, William E Jenkinson, Graham Anderson
Most αβ T cells that form in the thymus are generated during mainstream conventional thymocyte development and involve the generation and selection of a diverse αβ TCR repertoire that recognizes self-peptide/MHC complexes. Additionally, the thymus also supports the production of T cell subsets that express αβ TCRs but display unique developmental and functional features distinct from conventional αβ T cells. These include multiple lineages of CD1d-restricted invariant NKT (iNKT) cells that express an invariant αβ TCR, branch off from mainstream thymocytes at the CD4+ CD8+ stage, and are potent producers of polarizing cytokines...
May 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29731839/high-frequency-of-circulating-follicular-helper-t-cells-is-correlated-with-b-cell-subtypes-in-patients-with-ankylosing-spondylitis
#20
Siqi Long, Li Ma, Dongsheng Wang, Xianwen Shang
T follicular helper (Tfh) cells are known to support effector B cells and enhance autoimmunity; however, the association between the Tfh cells and B cells in ankylosing spondylitis (AS) is unclear. The aim of the present study was to measure the frequency of circulating cluster of differentiation (CD)4+ C-X-C chemokine receptor type 5 (CXCR5)+ Tfh cells and B cell subtypes in peripheral blood from patients with AS, and evaluate the correlation of these factors. Percentages of peripheral blood circulating CD4+ CXCR5+ Tfh cells and B cell subtypes were measured via flow cytometry and the disease activity of individual patients was measured using the Bath AS Disease Activity Index (BASDAI)...
May 2018: Experimental and Therapeutic Medicine
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