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CD8 tolerance

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https://www.readbyqxmd.com/read/28321218/the-induction-and-maintenance-of-transplant-tolerance-engages-both-regulatory-and-anergic-cd4-t-cells
#1
Alix Besançon, Marije Baas, Tania Goncalves, Fabrice Valette, Herman Waldmann, Lucienne Chatenoud, Sylvaine You
Therapeutic tolerance to self-antigens or foreign antigens is thought to depend on constant vigilance by Foxp3(+) regulatory T cells (Tregs). Previous work using a pancreatic islet allograft model and a short pulse of CD3 antibody therapy has shown that CD8(+) T cells become anergic and use TGFβ and coinhibitory signaling as their contribution to the tolerance process. Here, we examine the role of CD4(+) T cells in tolerization by CD3 antibodies. We show that both Foxp3(+) Tregs and CD4(+) T cell anergy play a role in the induction of tolerance and its maintenance...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28284988/frequencies-of-pd-1-positive-t-cd3-cd4-t-cd3-cd8-and-b%C3%A2-cd19-lymphocytes-in-female-patients-with-graves-disease-and-healthy-controls-preliminary-study
#2
Aleksandra Pyzik, Ewelina Grywalska, Beata Matyjaszek-Matuszek, Agata Smoleń, Dawid Pyzik, Jacek Roliński
PD-1 maintains tolerance and inhibits autoimmune responses. Graves' disease (GD) is one of the most frequent autoimmune diseases of unclear etiology. The aim of this study was to evaluate the percentage and absolute counts of PD-1 positive T and B cells in newly diagnosed, untreated patients with hyperthyroidism due to GD. The study group included 30 patients and the control group comprised of 20 age- and sex-matched healthy individuals. Results showed significantly higher frequencies and absolute counts of PD-1 positive CD3+CD4+ T cells, CD3+CD8+ T cells and CD19+B cells in patients with GD in comparison to the healthy volunteers...
March 8, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28284982/the-balance-between-cd8-t-cell-mediated-clearance-of-aav-encoded-antigen-in-the-liver-and-tolerance-is-dependent-on-the-vector-dose
#3
Sandeep R P Kumar, Brad E Hoffman, Cox Terhorst, Ype P de Jong, Roland W Herzog
The liver continuously receives antigens from circulation and the gastrointestinal tract. A complex immune regulatory system has evolved in order to both limit inflammation and promote tolerance in the liver. Although in situ immune tolerance mechanisms enable successful gene therapy and liver transplantation, at the same time they facilitate chronic infections by pathogens such as hepatitis viruses. It is, however, poorly understood why hepatocytes infected with hepatitis viruses or transduced with adeno-associated virus (AAV)-based vectors may be rejected by CD8(+) T cells several months later...
March 8, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28273209/influence-of-treg-cells-and-hbv-genotype-on-sustained-response-and-drug-resistance-in-the-treatment-with-nucleoside-drugs
#4
Y R Zhang, B Li, C X Wang, N Zhou, W Qi, X L Li, L Y Wu, S F Wei, Y D Zhang
We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group...
March 2, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28270614/engineered-erythrocytes-covalently-linked-to-antigenic-peptides-can-protect-against-autoimmune-disease
#5
Novalia Pishesha, Angelina M Bilate, Marsha C Wibowo, Nai-Jia Huang, Zeyang Li, Rhogerry Dhesycka, Djenet Bousbaine, Hojun Li, Heide C Patterson, Stephanie K Dougan, Takeshi Maruyama, Harvey F Lodish, Hidde L Ploegh
Current therapies for autoimmune diseases rely on traditional immunosuppressive medications that expose patients to an increased risk of opportunistic infections and other complications. Immunoregulatory interventions that act prophylactically or therapeutically to induce antigen-specific tolerance might overcome these obstacles. Here we use the transpeptidase sortase to covalently attach disease-associated autoantigens to genetically engineered and to unmodified red blood cells as a means of inducing antigen-specific tolerance...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28263308/autoimmunity-against-a-defective-ribosomal-insulin-gene-product-in-type-1-diabetes
#6
Maria J L Kracht, Menno van Lummel, Tatjana Nikolic, Antoinette M Joosten, Sandra Laban, Arno R van der Slik, Peter A van Veelen, Françoise Carlotti, Eelco J P de Koning, Rob C Hoeben, Arnaud Zaldumbide, Bart O Roep
Identification of epitopes that are recognized by diabetogenic T cells and cause selective beta cell destruction in type 1 diabetes (T1D) has focused on peptides originating from native beta cell proteins. Translational errors represent a major potential source of antigenic peptides to which central immune tolerance is lacking. Here, we describe an alternative open reading frame within human insulin mRNA encoding a highly immunogenic polypeptide that is targeted by T cells in T1D patients. We show that cytotoxic T cells directed against the N-terminal peptide of this nonconventional product are present in the circulation of individuals diagnosed with T1D, and we provide direct evidence that such CD8(+) T cells are capable of killing human beta cells and thereby may be diabetogenic...
February 27, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28257995/regulatory-b-cells-phenotype-function-and-role-in-transplantation
#7
REVIEW
C M Wortel, S Heidt
While B cells are traditionally known for their roles in antibody production, antigen presentation and cytokine production, recent studies have highlighted the existence of B cells with regulatory properties, which have been termed Bregs, analogous to regulatory T cells (Tregs). Bregs have been found to play a role in autoimmune disease, malignancies, infections, and may also be involved in solid organ transplantation. Their main mechanism of action is by promoting the development of Tregs while suppressing effector CD4(+) and CD8(+) T cells, primarily by IL-10 secretion...
March 1, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28255727/studying-dendritic-cell-t-cell-interactions-under-in-vivo-conditions
#8
Nicholas van Panhuys
The interactions between dendritic cells and T cells during the initiation of an adaptive immune response underpins one of the most important checkpoints in ensuring that the correct immune response is induced, in order to direct the development of immune tolerance or to mount an immune response against pathogenic organisms. The advent of two-photon intravital imaging allows us to directly study the interactions between dendritic cells and T cells as they occur under physiological conditions, greatly improving our understanding of the dynamic relationship that occurs during T cell activation and expanding our knowledge of how the adaptive immune system is regulated during both priming and memory responses...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28251801/origin-of-enriched-regulatory-t-cells-in-patients-receiving-combined-kidney-bone-marrow-transplantation-to-induce-transplantation-tolerance
#9
Ben Sprangers, Susan DeWolf, Thomas M Savage, Tatsuaki Morokata, Aleksandar Obradovic, Samuel A LoCascio, Brittany Shonts, Julien Zuber, Sai Ping Lau, Ravi Shah, Heather Morris, Valeria Steshenko, Emmanuel Zorn, Frederic I Preffer, Sven Olek, David M Dombkowski, Laurence A Turka, Robert Colvin, Robert Winchester, Tatsuo Kawai, Megan Sykes
We examined tolerance mechanisms in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT) that led to transient chimerism under a previously-published non-myeloablative conditioning regimen (Immune Tolerance Network study ITN036). Polychromatic flow cytometry (FCM) and high throughput sequencing of TCRβ hypervariable regions of DNA from peripheral blood T regulatory cells (Tregs) and CD4 non-Tregs revealed marked early enrichment of regulatory T cells (CD3(+) CD4(+) CD25(high) CD127(low) Foxp3(+) ) in blood that resulted from peripheral proliferation (Ki67(+) ), possibly new thymic emigration (CD31(+) ) and, in one tolerant subject, conversion from non-Tregs...
March 1, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28239381/presentation-of-autoantigen-in-peripheral-lymph-nodes-is-sufficient-for-priming-autoreactive-cd8-t-cells
#10
Nadine Honke, Namir Shaabani, John R Teijaro, Urs Christen, Cornelia Hardt, Judith Bezgovsek, Philipp A Lang, Karl S Lang
Peripheral tolerance is an important mechanism by which the immune system can guarantee a second line of defense against autoreactive T and B cells. One autoimmune disease that is related to a break of peripheral tolerance is diabetes mellitus type 1. Using the RIP-GP mouse model, we analyzed the role of the spleen and lymph nodes (LNs) in priming CD8(+) T cells and breaking peripheral tolerance. We found that diabetes developed in splenectomized mice infected with the lymphocytic choriomeningitis virus (LCMV), a finding showing that the spleen was not necessary in generating autoimmunity...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28237837/a-novel-dna-vaccine-platform-enhances-neo-antigen-like-t-cell-responses-against-wt1-to-break-tolerance-and-induce-anti-tumor-immunity
#11
Jewell N Walters, Bernadette Ferraro, Elizabeth K Duperret, Kimberly A Kraynyak, Jaemi Chu, Ashley Saint-Fleur, Jian Yan, Hy Levitsky, Amir S Khan, Niranjan Y Sardesai, David B Weiner
Tumor-associated antigens have emerged as important immunotherapeutic targets in the fight against cancer. Germline tumor antigens, such as WT1, Wilms' tumor gene 1, are overexpressed in many human malignancies but have low expression in somatic tissues. Recent vaccination approaches to target WT1 have been hampered by poor in vivo immune potency, likely due to the conserved self-antigen nature of WT1. In this study, we use a novel synthetic micro-consensus SynCon DNA vaccine approach with the goal of breaking tolerance and increasing vaccine immune potency...
February 22, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28235976/immune-regulation-of-intrahepatic-regulatory-t-cells-in-fibrotic-livers-of-mice
#12
Xiaohui Zhang, Jinli Lou, Li Bai, Yu Chen, Sujun Zheng, Zhongping Duan
BACKGROUND Liver fibrosis is the result of chronic inflammation and repair, and many immune cells contribute to the process. Regulatory T cells (Tregs) mediate immune tolerance and are highly expressed in liver fibrosis. However, few reports have studied the specific effects of Tregs on regulating immune cells in liver fibrosis. The present study aimed to investigate the regulation of Tregs on intrahepatic immune cells in liver fibrosis by depleting Tregs in mice. MATERIAL AND METHODS Liver fibrosis was induced by carbon tetrachloride, and an anti-CD25 mAb (PC61) was used to deplete Tregs...
February 25, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28228759/interleukin-35-producing-cd8%C3%AE-dendritic-cells-acquire-a-tolerogenic-state-and-regulate-t-cell-function
#13
Sergio Haller, Anaïs Duval, Romain Migliorini, Mathias Stevanin, Vanessa Mack, Hans Acha-Orbea
Dendritic cells (DCs) play a central role in shaping immunogenic as well as tolerogenic adaptive immune responses and thereby dictate the outcome of adaptive immunity. Here, we report the generation of a CD8α(+) DC line constitutively secreting the tolerogenic cytokine interleukin (IL)-35. IL-35 secretion led to impaired CD4(+) and CD8(+) T lymphocyte proliferation and interfered with their function in vitro and also in vivo. IL-35 was furthermore found to induce a tolerogenic phenotype on CD8α(+) DCs, characterized by the upregulation of CD11b, downregulation of MHC class II, a reduced costimulatory potential as well as production of the immunomodulatory molecule IL-10...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28214886/adenovirus-vector-harboring-the-hbcag-and-tripeptidyl-peptidase-ii-genes-induces-potent-cellular-immune-responses-in-vivo
#14
Quanhui Tan, Siyuan Ma, Jianjun Hu, Xiaohua Chen, Yongsheng Yu, Zhenghao Tang, Guoqin Zang
BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a weak but specific cellular immune response of the host to HBV. Tripeptidyl peptidaseⅡ (TPPⅡ), an intracellular macromolecule and proteolytic enzyme, plays an important complementary and compensatory role for the proteasome during viral protein degradation and major histocompatibility complex class I antigen presentation by inducing a specific cellular immune response in vivo. Based on a previous study, we aimed to explore the role of MHC class I antigen presentation in vivo and the mechanisms that may be involved...
January 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28194440/transient-antibody-targeting-of-cd45rc-induces-transplant-tolerance-and-potent-antigen-specific-regulatory-t-cells
#15
Elodie Picarda, Séverine Bézie, Laetitia Boucault, Elodie Autrusseau, Stéphanie Kilens, Dimitri Meistermann, Bernard Martinet, Véronique Daguin, Audrey Donnart, Eric Charpentier, Laurent David, Ignacio Anegon, Carole Guillonneau
Rat and human CD4(+) and CD8(+) Tregs expressing low levels of CD45RC have strong immunoregulatory properties. We describe here that human CD45 isoforms are nonredundant and identify distinct subsets of cells. We show that CD45RC is not expressed by CD4(+) and CD8(+) Foxp3(+) Tregs, while CD45RA/RB/RO are. Transient administration of a monoclonal antibody (mAb) targeting CD45RC in a rat cardiac allotransplantation model induced transplant tolerance associated with inhibition of allogeneic humoral responses but maintained primary and memory responses against cognate antigens...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28188748/association-between-high-avidity-t-cell-receptors-induced-by-alpha-fetoprotein-derived-peptides-and-anti-tumor-effects-in-patients-with-hepatocellular-carcinoma
#16
Hidetoshi Nakagawa, Eishiro Mizukoshi, Eiji Kobayashi, Toshikatsu Tamai, Hiroshi Hamana, Tatsuhiko Ozawa, Hiroyuki Kishi, Masaaki Kitahara, Tatsuya Yamashita, Kuniaki Arai, Takeshi Terashima, Noriho Iida, Kazumi Fushimi, Atsushi Muraguchi, Shuichi Kaneko
BACKGROUND & AIMS: Levels of alpha fetoprotein (AFP) are measured for surveillance and diagnosis of hepatocellular carcinoma (HCC). We performed a phase 1 trial to evaluate the safety and efficacy of AFP-derived peptides as an anti-tumor vaccine for patients with advanced HCC, and characterized induction of AFP-specific T-cell receptors (TCRs). METHODS: We performed a prospective study, of 15 patients with HCC seen at Kanazawa University Hospital in Japan from March 2010 through March 2012...
February 7, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28188334/aicar-ameliorates-high-fat-diet-associated-pathophysiology-in-mouse-and-ex-vivo-models-independent-of-adiponectin
#17
Emma Börgeson, Ville Wallenius, Gulam H Syed, Manjula Darshi, Juan Lantero Rodriguez, Christina Biörserud, Malin Ragnmark Ek, Per Björklund, Marianne Quiding-Järbrink, Lars Fändriks, Catherine Godson, Kumar Sharma
AIMS/HYPOTHESIS: In this study, we aimed to evaluate the therapeutic potential of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMP-activated protein kinase, for ameliorating high-fat diet (HFD)-induced pathophysiology in mice. We also aimed to determine whether the beneficial effects of AICAR were dependent on adiponectin. Furthermore, human adipose tissue was used to examine the effect of AICAR ex vivo. METHODS: Six-week-old male C57BL/6J wild-type and Adipoq (-/-) mice were fed a standard-fat diet (10% fat) or an HFD (60% fat) for 12 weeks and given vehicle or AICAR (500 μg/g) three times/week from weeks 4-12...
April 2017: Diabetologia
https://www.readbyqxmd.com/read/28179531/toll-like-receptor-7-agonist-gs-9620-induces-hiv-expression-and-hiv-specific-immunity-in-cells-from-hiv-infected-individuals-on-suppressive-antiretroviral-therapy
#18
Angela Tsai, Alivelu Irrinki, Jasmine Kaur, Tomas Cihlar, George Kukolj, Derek D Sloan, Jeffrey P Murry
Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs)...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28178038/p-selectin-glycoprotein-ligand-1-in-t-cells
#19
Michael Abadier, Klaus Ley
PURPOSE OF REVIEW: We review P-selectin glycoprotein ligand-1 (PSGL-1) as a selectin and chemokine-binding adhesion molecule. PSGL-1 is widely studied in neutrophils. Here, we focus on T cells, because PSGL-1 was recently described as a major immunomodulatory molecule during viral infection. PSGL-1 also plays a crucial role in T-cell homeostasis by binding to lymphoid chemokines, and can induce tolerance by enhancing the functions of regulatory T cells. RECENT FINDINGS: PSGL-1 was originally described as a leukocyte ligand for P-selectin, but it is actually a ligand for all selectins (P-, L- and E-selectin), binds chemokines, activates integrins and profoundly affects T-cell biology...
February 7, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28176796/depurinized-milk-downregulates-rat-thymus-myd88-akt-p38-function-nf-%C3%AE%C2%BAb-mediated-inflammation-caspase-1-activity-but-not-the-endonuclease-pathway-in-vitro-in-vivo-study
#20
Gordana Kocic, Andrej Veljkovic, Hristina Kocic, Miodrag Colic, Dusan Mihajlovic, Katarina Tomovic, Svetlana Stojanovic, Andrija Smelcerovic
The aim of this study was the evaluation of 15 days dietary regimen of depurinized (DP) milk (obtained using our patented technological procedures) or 1.5% fat UHT milk instead of standard chow diet, on rat thymus and bone marrow MyD88/Akt/p38, NF-κB, caspase-1 and endonuclease pathways, in relation to peripheral blood cell composition. To determine whether the reduced mass of the thymus is a consequence of the direct effect of DP/UHT milk on apoptosis of thymocytes, in vitro Annexin-V-FITC/PI assay was performed...
February 8, 2017: Scientific Reports
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