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CD8 tolerance

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https://www.readbyqxmd.com/read/28228759/interleukin-35-producing-cd8%C3%AE-dendritic-cells-acquire-a-tolerogenic-state-and-regulate-t-cell-function
#1
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
#2
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
#3
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
#4
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
#5
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...
February 10, 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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/28167776/tgf-%C3%AE-inhibitor-smad7-regulates-dendritic-cell-induced-autoimmunity
#9
Dominika Lukas, Nir Yogev, Junda M Kel, Tommy Regen, Ilgiz A Mufazalov, Yilang Tang, Florian Wanke, Boris Reizis, Werner Müller, Florian C Kurschus, Marco Prinz, Ingo Kleiter, Björn E Clausen, Ari Waisman
TGF-β is an anti-inflammatory cytokine whose signaling is negatively controlled by Smad7. Previously, we established a role for Smad7 in the generation of autoreactive T cells; however, the function of Smad7 in dendritic cells (DCs) remains elusive. Here, we demonstrate that DC-specific Smad7 deficiency resulted in elevated expression of the transcription factors Batf3 and IRF8, leading to increased frequencies of CD8(+)CD103(+) DCs in the spleen. Furthermore, Smad7-deficient DCs expressed higher levels of indoleamine 2,3-dioxygenase (IDO), an enzyme associated with tolerance induction...
February 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28164523/effect-of-serum-vitamin-d-levels-on-cellular-immunity-and-antiviral-effects-in-chronic-hepatitis-b-patients
#10
Li-Jie He, He-Ping Zhang, Hong-Juan Li, Jing Wang, Dan-Dan Chang
BACKGROUND: To study the effect of 25-hydroxyl vitamin D3 on peripheral blood T lymphocyte immune function and antiviral effects in chronic hepatitis B patients. METHODS: The clinical data for 70 patients with chronic hepatitis B were analyzed. Serum 25-hydroxyl vitamin D was determined by electrochemical luminescence, and hepatitis B virus serological markers were determined by fluorescence quantitative polymerase chain reaction. Subsets of T lymphocytes were determined by immune fluorescence labeling method...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28133807/host-controls-of-hiv-broadly-neutralizing-antibody-development
#11
REVIEW
Garnett Kelsoe, Barton F Haynes
Induction of broadly neutralizing antibodies (bNAbs) is a major goal of HIV vaccine development. BNAbs are made during HIV infection by a subset of individuals but currently cannot be induced in the setting of vaccination. Considerable progress has been made recently in understanding host immunologic controls of bNAb induction and maturation in the setting of HIV infection, and point to key roles for both central and peripheral immunologic tolerance mechanisms in limiting bnAb development. Immune tolerance checkpoint inhibition has been transformative in promotion of anti-tumor CD8 T-cell responses in the treatment of certain malignancies...
January 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28129932/chemokine-receptor-cxcr3-deficiency-exacerbates-murine-autoimmune-cholangitis-by-promoting-pathogenic-cd8-t-cell-activation
#12
Hong-Di Ma, Wen-Tao Ma, Qing-Zhi Liu, Zhi-Bin Zhao, Mu-Zi-Ying Liu, Koichi Tsuneyama, Jin-Ming Gao, William M Ridgway, Aftab A Ansari, M Eric Gershwin, Yun-Yun Fei, Zhe-Xiong Lian
CXC Chemokine Receptor 3 (CXCR3) is functionally pleiotropic and not only plays an important role in chemotaxis, but also participates in T cell differentiation and may play a critical role in inducing and maintaining immune tolerance. These observations are particularly critical for autoimmune cholangitis in which CXCR3 positive T cells are found around the portal areas of both humans and mouse models of primary biliary cholangitis (PBC). Herein, we investigated the role of CXCR3 in the pathogenesis of autoimmune cholangitis...
January 24, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28127757/donor-bone-marrow-cells-are-essential-for-inkt-cell-mediated-foxp3-treg-cell-expansion-in-a-murine-model-of-transplantation-tolerance
#13
Satoshi Miyairi, Toshihito Hirai, Rumi Ishii, Masayoshi Okumi, Shinichi Nunoda, Kenji Yamazaki, Yasuyuki Ishii, Kazunari Tanabe
Mixed chimerism induction is the most reliable method for establishing transplantation tolerance. We previously described a novel treatment using a suboptimal dose of anti-CD40 ligand (anti-CD40L) and liposomal formulation of a ligand for invariant natural killer T cells administered to sub-lethally irradiated recipient mice after donor bone marrow cell (BMC) transfer. Recipient mice treated with this regimen showed expansion of a Foxp3-positive regulatory T(Treg) cell phenotype, and formation of mixed chimera...
January 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28123634/memory-cd4-t-cells-are-suppressed-by-cd8-regulatory-t-cells-in-vitro-and-in-vivo
#14
Xin Long, Qi Cheng, Huifang Liang, Jianping Zhao, Jian Wang, Wei Wang, Stephen Tomlinson, Lin Chen, Carl Atkinson, Bixiang Zhang, Xiaoping Chen, Peng Zhu
BACKGROUND: Acute graft rejection mediated by alloreactive memory CD4(+) T cells is a major obstacle to transplantation tolerance. It has been reported that CD8(+) T regulatory cells (Tregs) have the ability to induce graft tolerance by restraining the function of activated CD4(+) T cells, but not including memory T cells. The aim of this study is to elucidate the effect of CD8(+) Tregs on alloreactive memory CD4(+) T cells. METHODS: We detected Qa-1 expression and performed proliferative assay on memory CD4(+) T cells...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28120329/constitutive-expression-of-the-anti-apoptotic-bcl-2-family-member-a1-in-murine-endothelial-cells-leads-to-transplant-tolerance
#15
Lesley A Smyth, Lucy Meader, Fang Xiao, Martin Woodward, Hugh J Brady, Robert Lechler, Giovanna Lombardi
Anti-apoptotic genes including those of the Bcl-2 family have been shown to have dual functionality in as much as they inhibit cell death but also regulate inflammation. Several anti-apoptotic molecules have been associated with endothelial cell (EC) survival following transplantation however their exact role has yet to be elucidated in respect to controlling inflammation. In this study we created mice expressing murine A1 (Bfl-1), a Bcl-2 family member, under the control of the human ICAM-2 promoter. Constitutive expression of A1 in murine vascular ECs conferred protection from cell death induced by the pro-inflammatory cytokine TNF-α...
January 24, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28110884/tumor-antigen-specific-cd8-t-cells-are-negatively-regulated-by-pd-1-and-tim-3-in-human-gastric-cancer
#16
Xu Lu, Lin Yang, Daxing Yao, Xuan Wu, Jingpo Li, Xuesong Liu, Lijuan Deng, Caiting Huang, Yue Wang, Dan Li, Jingwei Liu
Cytotoxic CD8 T lymphocytes that are present in tumors and capable of recognizing tumor epitopes are nevertheless generally important in eliciting tumor rejection. NY-ESO-1 is a major target of CD8(+) T cell recognition in gastric cancer (GC) and is among the most immunogenic tumor antigens defined to date. Thus, identifying the immune escape mechanisms responsible for inducing tumor-specific CD8(+) T cell dysfunction may reveal effective strategies for immunotherapy. In an effort to understand in vivo tolerance mechanisms, we assessed the phenotype and function of NY-ESO-1-specific CD8(+) T cells derived from peripheral blood lymphocytes (PBLs) and tumor-associated lymphocytes (TALs) of GC patients...
January 5, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28109025/immune-regulation-by-t-regulatory-cells-in-hbv-related-inflammation-and-cancer
#17
REVIEW
Nirupama Trehanpati, Ashish Kumar Vyas
Hepatocellular carcinoma (HCC) is the leading cause of cancer death and hepatitis B virus (HBV) infection is one of the commonest causes in Asians countries. India has the second largest pool after China for hepatitis B infected subjects. HBV clearance is T cell dependent and one of the reason for T cells hypo responsiveness is due to mass production of Tregs through activation of Notch signaling, which suppressCD4/CD8 T cells. Regulatory T cells (Tregs) are important to maintain cellular homeostasis; however during viral infection increase of Tregs is inversely proportional to HBV DNA titers...
January 21, 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28106145/cd1-and-cd1-porcine-blood-dendritic-cells-are-enriched-for-the-orthologues-of-the-two-major-mammalian-conventional-subsets
#18
Jane C Edwards, Helen E Everett, Miriam Pedrera, Helen Mokhtar, Emanuele Marchi, Ferran Soldevila, Daryan A Kaveh, Philip J Hogarth, Helen L Johns, Javier Nunez-Garcia, Falko Steinbach, Helen R Crooke, Simon P Graham
Conventional dendritic cells (cDC) are professional antigen-presenting cells that induce immune activation or tolerance. Two functionally specialised populations, termed cDC1 and cDC2, have been described in humans, mice, ruminants and recently in pigs. Pigs are an important biomedical model species and a key source of animal protein; therefore further understanding of their immune system will help underpin the development of disease prevention strategies. To characterise cDC populations in porcine blood, DC were enriched from PBMC by CD14 depletion and CD172a enrichment then stained with lineage mAbs (Lin; CD3, CD8α, CD14 and CD21) and mAbs specific for CD172a, CD1 and CD4...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105230/dendritic-cell-activated-cytokine-induced-killer-cell-mediated-immunotherapy-is-safe-and-effective-for-cancer-patients-65-years-old
#19
Yanfeng Liu, Haibo Liu, Hausheng Liu, Pengcheng He, Jing Li, Xin Liu, Limei Chen, Mengchang Wang, Jiejing Xi, Huaiyu Wang, Haitao Zhang, Ying Zhu, Wei Zhu, Jing Ning, Caili Guo, Chunhong Sun, Mei Zhang
Individuals >65 years old account for a large proportion of cancer patients, and usually have poor prognoses due to relative weaker physiological function and lower drug tolerance. To characterize the efficacy and safety of dendritic cell (DC)-activated cytokine-induced killer cell (CIK)-mediated treatment, and develop an adoptive immunotherapy for cancer patients >65 years old, a retrospective study was performed in 58 cancer sufferers who received 1-4 cycles of DC-activated CIK (DC-CIK) treatment and evaluated the response (tumor remission rate) and toxicity (side effects to the treatment)...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28096089/tolerogenic-interactions-between-cd8-dendritic-cells-and-nkt-cells-prevent-rejection-of-bone-marrow-and-organ-grafts
#20
David Hongo, Xiaobin Tang, Xiangyue Zhang, Edgar G Engleman, Samuel Strober
The combination of total lymphoid irradiation and anti-T cell antibodies safely induces immune tolerance to combined hematopoietic cell and organ allografts in humans. Our mouse model required host natural killer T (NKT) cells to induce tolerance. Since NKT cells normally depend on signals from CD8+ dendritic cells (DCs) for their activation, we used the mouse model to test the hypothesis that after lymphoid irradiation host CD8+DCs play a requisite role in tolerance induction through interactions with NKT cells...
January 17, 2017: Blood
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