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https://www.readbyqxmd.com/read/28818684/t-cell-mediated-rejection-of-human-cd34-cells-is-prevented-by-costimulatory-blockade-in-a-xenograft-model
#1
A L Oh, D Mahmud, B Nicolini, N Mahmud, V Senyuk, P R Patel, E Bonetti, M Arpinati, Jlm Ferrara, D Rondelli
A xenograft model of stem cell rejection was developed by co-transplantating human CD34+ and allogeneic CD3+ T cells into NOD-scid ɣ-chain(null) (NSG) mice. T cells caused graft failure when transplanted at any CD34:CD3 ratio between 1:50 to 1:0.1. Kinetics experiments showed that two weeks after transplantation CD34+ cells engrafted the marrow and T cells expanded in the spleen. Then at four weeks only memory T cells populated both sites and rejected CD34+ cells. Blockade of T cell costimulation was tested by injecting the mice with abatacept (CTLA4-IgG1) from day -1 to +27 (Group A), or from day -1 to +13 (Group B), or from day +14 to +28 (Group C)...
August 14, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28817118/altered-marginal-zone-and-innate-like-b-cells-in-aged-senescence-accelerated-samp8-mice-with-defective-igg1-responses
#2
Isabel Cortegano, Mercedes Rodríguez, Isabel Martín, Maria Carmen Prado, Carolina Ruíz, Rafael Hortigüela, Mario Alía, Marçal Vilar, Helena Mira, Eva Cano, Mercedes Domínguez, Belén de Andrés, María Luisa Gaspar
Aging has a strong impact on the activity of the immune system, enhancing susceptibility to pathogens and provoking a predominant pre-inflammatory status, whereas dampening responses to vaccines in humans and mice. Here, we demonstrate a loss of marginal zone B lymphocytes (MZ, CD19(+)CD45R(+)CD21(++)CD23(lo)) and a decrease of naive B cells (CD19(+)IgD(+)), whereas there is an enhancement of a CD19(+)CD45R(lo) innate-like B cell population (B1REL) and the so-called aged B cell compartment (ABC, CD45R(+)CD21(lo)CD23(lo)CD5(-)CD11b(-)) in aged senescence-accelerated (SAMP8) mice but not in aged senescence-resistant (SAMR1) mice...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28817117/increased-tumor-infiltrating-cd45ra-ccr7-regulatory-t-cell-subset-with-immunosuppressive-properties-foster-gastric-cancer-progress
#3
Fang-Yuan Mao, Hui Kong, Yong-Liang Zhao, Liu-Sheng Peng, Weisan Chen, Jin-Yu Zhang, Ping Cheng, Ting-Ting Wang, Yi-Pin Lv, Yong-Sheng Teng, Xiao-Long Fu, Yu-Gang Liu, Xiao-Long Wu, Chuan-Jie Hao, Nan You, Ping Luo, Pei-Wu Yu, Quan-Ming Zou, Gang Guo, Yuan Zhuang
Regulatory T cells (Tregs) are major components of tumor-infiltrating immune cells with potent immunosuppressive properties in gastric cancer (GC) microenvironment. However, different subsets of the Tregs and their relevance to GC are unknown. Here, we found that patients with GC showed a significantly higher Tregs infiltration in tumors, and CD45RA(-)CCR7(-) Treg subset constituted most tumor-infiltrating Tregs. Tumor-infiltrating CD45RA(-)CCR7(-) Treg subset with an effector/memory phenotype accumulated in tumors and expressed low level of HLA-DR...
August 17, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28815584/maintenance-of-cd8-memory-t-lymphocytes-in-the-spleen-but-not-in-the-bone-marrow-is-dependent-on-proliferation
#4
Francesco Siracusa, Özen Sercan Alp, Patrick Maschmeyer, Mairi McGrath, Mir-Farzin Mashreghi, Shintaro Hojyo, Hyun-Dong Chang, Koji Tokoyoda, Andreas Radbruch
It is current belief that numbers of CD8 memory T lymphocytes in the memory phase of an immune response are maintained by homeostatic proliferation. Here we compare the proliferation of CD8 memory T lymphocytes, generated by natural infections and by intentional immunization, in spleen and in bone marrow. 50% of CD8 memory T lymphocytes in the spleen are eliminated by cyclophosphamide within 14 days, indicating that numbers of at least 50% of splenic CD8 memory T lymphocytes are maintained by proliferation...
August 16, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28815218/capturing-the-systemic-immune-signature-of-a-norovirus-infection-an-n-of-1-case-study-within-a-clinical-trial
#5
Antony J Cutler, Joao Oliveira, Ricardo C Ferreira, Ben Challis, Neil M Walker, Sarah Caddy, Jia Lu, Helen E Stevens, Deborah J Smyth, Marcin L Pekalski, Jane Kennet, Kara M D Hunter, Ian Goodfellow, Linda S Wicker, John A Todd, Frank Waldron-Lynch
BACKGROUND:  The infection of a participant with norovirus during the adaptive study of interleukin-2 dose on regulatory T cells in type 1 diabetes (DILT1D) allowed a detailed insight into the cellular and cytokine immune responses to this prevalent gastrointestinal pathogen. METHODS:  Serial blood, serum and peripheral blood mononuclear cell (PBMC) samples were collected pre-, and post-development of the infection. To differentiate between the immune response to norovirus and to control for the administration of a single dose of aldesleukin (recombinant interleukin-2, rIL-2) alone, samples from five non-infected participants administered similar doses were analysed in parallel...
2017: Wellcome Open Research
https://www.readbyqxmd.com/read/28814669/neonatal-and-adult-recent-thymic-emigrants-produce-il-8-and-express-complement-receptors-cr1-and-cr2
#6
Marcin L Pekalski, Arcadio Rubio García, Ricardo C Ferreira, Daniel B Rainbow, Deborah J Smyth, Meghavi Mashar, Jane Brady, Natalia Savinykh, Xaquin Castro Dopico, Sumiyya Mahmood, Simon Duley, Helen E Stevens, Neil M Walker, Antony J Cutler, Frank Waldron-Lynch, David B Dunger, Claire Shannon-Lowe, Alasdair J Coles, Joanne L Jones, Chris Wallace, John A Todd, Linda S Wicker
The maintenance of peripheral naive T lymphocytes in humans is dependent on their homeostatic division, not continuing emigration from the thymus, which undergoes involution with age. However, postthymic maintenance of naive T cells is still poorly understood. Previously we reported that recent thymic emigrants (RTEs) are contained in CD31+CD25- naive T cells as defined by their levels of signal joint T cell receptor rearrangement excision circles (sjTRECs). Here, by differential gene expression analysis followed by protein expression and functional studies, we define that the naive T cells having divided the least since thymic emigration express complement receptors (CR1 and CR2) known to bind complement C3b- and C3d-decorated microbial products and, following activation, produce IL-8 (CXCL8), a major chemoattractant for neutrophils in bacterial defense...
August 17, 2017: JCI Insight
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...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28811646/pafah1b1-haploinsufficiency-disrupts-gaba-neurons-and-synaptic-e-i-balance-in-the-dentate-gyrus
#8
Matthew T Dinday, Kelly M Girskis, Sunyoung Lee, Scott C Baraban, Robert F Hunt
Hemizygous mutations in the human gene encoding platelet-activating factor acetylhydrolase IB subunit alpha (Pafah1b1), also called Lissencephaly-1, can cause classical lissencephaly, a severe malformation of cortical development. Children with this disorder suffer from deficits in neuronal migration, severe intellectual disability, intractable epilepsy and early death. While many of these features can be reproduced in Pafah1b1(+/-) mice, the impact of Pafah1b1(+/-) on the function of individual subpopulations of neurons and ultimately brain circuits is largely unknown...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811623/immune-dysregulation-in-patients-with-carpal-tunnel-syndrome
#9
Gila Moalem-Taylor, Benny Baharuddin, Barbara Bennett, Arun V Krishnan, William Huynh, Matthew C Kiernan, Cindy Shin-Yi Lin, Boaz Shulruf, Elizabeth Keoshkerian, Barbara Cameron, Andrew Lloyd
Peripheral immunity plays a key role in maintaining homeostasis and conferring crucial neuroprotective effects on the injured nervous system, while at the same time may contribute to increased vulnerability to neuropathic pain. Little is known about the reciprocal relationship between entrapment neuropathy and peripheral immunity. This study investigated immune profile in patients with carpal tunnel syndrome (CTS), the most prevalent entrapment neuropathy. All patients exhibited neurophysiological abnormalities in the median nerve, with the majority reporting neuropathic pain symptoms...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811600/exploring-leishmania-secretory-proteins-to-design-b-and-t-cell-multi-epitope-subunit-vaccine-using-immunoinformatics-approach
#10
Nazia Khatoon, Rajan Kumar Pandey, Vijay Kumar Prajapati
Visceral leishmaniasis (VL) is a fatal form of leishmaniasis which affects 70 countries, worldwide. Increasing drug resistance, HIV co-infection, and poor health system require operative vaccination strategy to control the VL transmission dynamics. Therefore, a holistic approach is needed to generate T and B memory cells to mediate long-term immunity against VL infection. Consequently, immunoinformatics approach was applied to design Leishmania secretory protein based multi-epitope subunit vaccine construct consisting of B and T cell epitopes...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810929/the-impact-of-age-and-gut-microbiota-on-th17-and-tfh-cells-in-k-bxn-autoimmune-arthritis
#11
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/28810548/effect-of-follicular-helper-t-cells-on-the-pathogenesis-of-asthma
#12
Xiaojuan Ma, Zhan Sun, Pei Zhai, Wenyan Yu, Ting Wang, Fengsen Li, Jianbing Ding
Follicular helper T (TFH) cells are considered to be a separate T helper cell subset, specifically to help memory B cell participate in humoral immunity. It has been reported that there is an association between the imbalance of TFH function and certain autoimmune diseases. However, to the best of our knowledge, the effect of TFH cells on the process of bronchial asthma has not been investigated. The aim of the present study was to investigate the associated markers of TFH cells in bronchial asthma-induced mice...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28807929/human-mucosal-associated-invariant-t-mait-cells-possess-capacity-for-b-cell-help
#13
Michael S Bennett, Shubhanshi Trivedi, Anita S Iyer, J Scott Hale, Daniel T Leung
Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell subset, restricted by the nonclassic MHC class I-related protein MR1 and enriched at mucosal sites. Human studies have shown an association between MAIT cells and pathogen-specific antibody responses. In this study, we investigate the effect of human MAIT cells on B cells ex vivo. We found that supernatants from microbe- or cytokine-stimulated MAIT cells, when added to purified autologous B cells, increase frequencies of plasmablasts and promote IgA, IgG, and IgM production...
August 14, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28804991/nf-%C3%AE%C2%BAb2-controls-migratory-activity-of-memory-t-cells-by-regulating-expression-of-cxcr4-in-a-mouse-model-of-sj%C3%A3-gren-s-syndrome
#14
Mie Kurosawa, Rieko Arakaki, Akiko Yamada, Takaaki Tsunematsu, Yasusei Kudo, Jonathan Sprent, Naozumi Ishimaru
OBJECTIVE: Dysregulated chemokine signaling contributes to autoimmune diseases by facilitating aberrant T-cell infiltration into target tissues, but the specific chemokines, receptors, and T-cell populations remain largely unidentified. Role of the potent chemokine CXCL12 and its receptor CXCR4 in T-cell autoimmune response was examined using alymphoplasia (aly)/aly mice, a Sjögren's syndrome (SS) model. METHODS: T-cell phenotypes in the salivary gland of aly/aly mice were evaluated using immunological analysis...
August 13, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28803568/history-of-child-maltreatment-and-telomere-length-in-immune-cell-subsets-associations-with-stress-and-attachment-related-hormones
#15
Christina Boeck, Sabrina Krause, Alexander Karabatsiakis, Katharina Schury, Harald Gündel, Christiane Waller, Iris-Tatjana Kolassa
Experiencing maltreatment during childhood can have long-lasting consequences for both mental and physical health. Immune cell telomere length (TL) shortening might be one link between child maltreatment (CM) experiences and adverse health outcomes later in life. While the stress hormone cortisol has been associated with TL attrition, the attachment-related hormone oxytocin may promote resilience. In 15 mothers with and 15 age- and body mass index-matched mothers without CM, we assessed TL in peripheral blood mononuclear cells and selected immune cell subsets (monocytes, naive, and memory cytotoxic T cells) by quantitative fluorescence in situ hybridization, as well as peripheral cortisol and oxytocin levels...
August 14, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28801345/molecular-basis-for-increased-susceptibility-of-indigenous-north-americans-to-seropositive-rheumatoid-arthritis
#16
Stephen W Scally, Soi-Cheng Law, Yi Tian Ting, Jurgen van Heemst, Jeremy Sokolove, Aaron J Deutsch, E Bridie Clemens, Antonis K Moustakas, George K Papadopoulos, Diane van der Woude, Irene Smolik, Carol A Hitchon, David B Robinson, Elizabeth D Ferucci, Charles N Bernstein, Xiaobo Meng, Vidyanand Anaparti, Tom Huizinga, Katherine Kedzierska, Hugh H Reid, Soumya Raychaudhuri, René E Toes, Jamie Rossjohn, Hani El-Gabalawy, Ranjeny Thomas
OBJECTIVE: The pathogenetic mechanisms by which HLA-DRB1 alleles are associated with anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) are incompletely understood. RA high-risk HLA-DRB1 alleles are known to share a common motif, the 'shared susceptibility epitope (SE)'. Here, the electropositive P4 pocket of HLA-DRB1 accommodates self-peptide residues containing citrulline but not arginine. HLA-DRB1 His/Phe13β stratifies with ACPA-positive RA, while His13βSer polymorphisms stratify with ACPA-negative RA and RA protection...
August 11, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28801292/-oxidized-low-density-lipoprotein-modulates-differentiation-of-murine-memory-cd8-t-cell-subpopulations
#17
Hua Zheng, Ze-Hang Lin, Yan-Mei Zhang, Chen-Fei Zhou, Xuan Liu, Sha Wu
OBJECTIVE: To investigate effect of oxidized low-density lipoprotein (ox-LDL) on memory CD8(+) T cell subpopulation differentiation in mice with autoimmune diabetes. METHODS: Cultured splenic CD8(+) T cells from pre-diabetic NOD mice isolated with magnetic beads were treated with 30 µg/mL ox-LDL and 10 U/mL interleukin-2 (IL-2) for 24 h and the control cells were treated with IL-2 only. Flow cytometry was used to determine the percentage of splenic CD8(+)IFN-γ(+) T cells, expressions of CD8, CD44 and CD62L on the T cells, and the activation of T cell factor-1 (TCF-1) and STAT-3...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28799643/sebocytes-contribute-to-skin-inflammation-by-promoting-the-differentiation-of-th17-cells
#18
M Mattii, M Lovászi, N Garzorz, A Atenhan, M Quaranta, F Lauffer, A Konstantinow, M Küpper, C C Zouboulis, L Kemeny, K Eyerich, C B Schmidt-Weber, D Törőcsik, S Eyerich
BACKGROUND: The main function of sebocytes is considered to be the lipid production for moisturizing the skin. However, it became recently apparent that sebocytes release chemokines and cytokines and respond to pro-inflammatory stimuli as well as presence of bacteria. OBJECTIVES: To analyze the functional communication between human sebocytes and T cells. METHODS: Immunofluorescence stainings for CD4 and IL-17 were performed on acne sections and healthy skin...
August 11, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28799233/stochastics-of-cellular-differentiation-explained-by-epigenetics-the-case-of-t-cell-differentiation-and-functional-plasticity
#19
REVIEW
Jaydeep Bhat, Johannes Helmuth, Guranda Chitadze, Léonce Kouakanou, Christian Peters, Martin Vingron, Ole Ammerpohl, Dieter Kabelitz
Epigenetic marks including histone modifications and DNA methylation are associated to the regulation of gene expression and activity. In addition, an increasing number of non-coding RNAs with regulatory activity on gene expression have been identified. Alongside, technological advancements allow for the analysis of these mechanisms with high resolution - up to the single-cell level. For instance, the assay for transposase-accessible chromatin using sequencing (ATAC-seq) simultaneously probes for chromatin accessibility and nucleosome positioning...
August 10, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28799202/immune-tolerance-induced-by%C3%A2-platelet-targeted-factor-viii-gene-therapy-in-hemophilia-a-mice-is-cd4%C3%A2-t-cell-mediated
#20
Y Chen, X Luo, J A Schroeder, J Chen, C K Baumgartner, J Hu, Q Shi
BACKGROUND: Immune responses are a major concern in gene therapy. Our previous studies demonstrated that platelet-targeted FVIII (2bF8) gene therapy together with in vivo drug-selection of transduced cells can rescue the bleeding diathesis and induce immune tolerance in FVIII(null) mice. OBJECTIVE: To investigate whether non-selectable 2bF8 lentiviral vector (LV) for the induction of platelet-FVIII expression is sufficient to induce immune tolerance and how immune tolerance is induced after 2bF8LV gene therapy...
August 11, 2017: Journal of Thrombosis and Haemostasis: JTH
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