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CD8 tolerance

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https://www.readbyqxmd.com/read/28077588/first-in-human-evaluation-of-the-safety-and-immunogenicity-of-an-intranasally-administered-replication-competent-sendai-virus-vectored-hiv-type-1-gag-vaccine-induction-of-potent-t-cell-or-antibody-responses-in-prime-boost-regimens
#1
Julien Nyombayire, Omu Anzala, Brian Gazzard, Etienne Karita, Philip Bergin, Peter Hayes, Jakub Kopycinski, Gloria Omosa-Manyonyi, Akil Jackson, Jean Bizimana, Bashir Farah, Eddy Sayeed, Christopher L Parks, Makoto Inoue, Takashi Hironaka, Hiroto Hara, Tsugumine Shu, Tetsuro Matano, Len Dally, Burc Barin, Harriet Park, Jill Gilmour, Angela Lombardo, Jean-Louis Excler, Patricia Fast, Dagna S Laufer, Josephine H Cox
BACKGROUND:  We report the first-in-human safety and immunogenicity assessment of a prototype intranasally administered, replication-competent Sendai virus (SeV)-vectored, human immunodeficiency virus type 1 (HIV-1) vaccine. METHODS:  Sixty-five HIV-1-uninfected adults in Kenya, Rwanda, and the United Kingdom were assigned to receive 1 of 4 prime-boost regimens (administered at 0 and 4 months, respectively; ratio of vaccine to placebo recipients, 12:4): priming with a lower-dose SeV-Gag given intranasally, followed by boosting with an adenovirus 35-vectored vaccine encoding HIV-1 Gag, reverse transcriptase, integrase, and Nef (Ad35-GRIN) given intramuscularly (SLA); priming with a higher-dose SeV-Gag given intranasally, followed by boosting with Ad35-GRIN given intramuscularly (SHA); priming with Ad35-GRIN given intramuscularly, followed by boosting with a higher-dose SeV-Gag given intranasally (ASH); and priming and boosting with a higher-dose SeV-Gag given intranasally (SHSH)...
January 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28077266/asp0028-in-combination-with-suboptimal-dose-of-tacrolimus-in-cynomolgus-monkey-renal-transplantation-model
#2
Hao Dun, Lijun Song, Anlun Ma, Yanxin Hu, Lin Zeng, Jieying Bai, Guangzhou Zhang, Liangyan Zhang, Kumi Koide, Yohei Okada, Kaori Hanaoka, Rie Yamamoto, Jun Hirose, Tatsuaki Morokata, Pierre Daloze, Huifang Chen
FTY720, a S1P-receptor modulator, has shown to be effective in several transplant and autoimmune disease models, via modulating lymphocyte homing into secondary lymphoid organs (SLOs), and thereby reducing these cells in peripheral blood. ASP0028, a newly developed S1P1/S1P5-selective agonist, presented comparable efficacy to FTY720 and wider safety margins than FTY720. In this study, we assessed the efficacy and safety of ASP0028 co-administered with suboptimal-dose of tacrolimus in the Cynomolgus monkey renal transplantation model...
January 7, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28066981/disruption-of-transplant-tolerance-by-an-incognito-form-of-cd8-t-cell-dependent-memory
#3
M K Nelsen, K S Beard, R J Plenter, R M Kedl, E T Clambey, R G Gill
Several approaches successfully achieve allograft tolerance in preclinical models but are challenging to translate into clinical practice. Many clinically relevant factors can attenuate allograft tolerance induction including intrinsic genetic resistance, peri-transplant infection, inflammation, and pre-existing anti-donor immunity. The prevailing view for immune memory as a tolerance barrier is that the host harbors memory cells that spontaneously cross-react to donor MHC antigens. Such pre-existing 'heterologous' memory cells have direct reactivity to donor cells and resist most tolerance regimens...
January 9, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28065449/a-specific-immune-tolerance-toward-offspring-cells-is-to-exist-after-the-mother-lymphocyte-infusion
#4
Haizhou Xing, Shiqin Liu, Xue Chen, Fang Fang, Xueqiang Wu, Ping Zhu
PURPOSE: To examine immune tolerance between maternal lymphocytes and offspring tissue after a donor lymphocyte infusion. METHODS: Mouse models were established by mating female BALB/c mice with male C57BL mice. Splenic lymphocytes from donors of different genetic backgrounds were labeled with carboxyfluorescein succinimidyl ester (CFSE), and 1×10(7) of the labeled cells were intravenously injected into a recipient. At 6h, 24h, 72h and 120h after the infusion, mononuclear cells in recipient spleen, liver, thymus, lymph nodes, and peripheral blood were collected...
December 26, 2016: Immunobiology
https://www.readbyqxmd.com/read/28052005/bortezomib-augments-lymphocyte-stimulatory-cytokine-signaling-in-the-tumor-microenvironment-to-sustain-cd8-t-cell-antitumor-function
#5
Samuel T Pellom, Duafalia F Dudimah, Menaka C Thounaojam, Roman V Uzhachenko, Ashutosh Singhal, Ann Richmond, Anil Shanker
Tumor-induced immune tolerance poses a major challenge for therapeutic interventions aimed to manage cancer. We explored approaches to overcome T-cell suppression in murine breast and kidney adenocarcinomas, and lung fibrosarcoma expressing immunogenic antigens. We observed that treatment with a reversible proteasome inhibitor bortezomib (1 mg/kg body weight) in tumor-bearing mice significantly enhanced the expression of lymphocyte-stimulatory cytokines IL-2, IL-12, and IL-15. Notably, bortezomib administration reduced pulmonary nodules of mammary adenocarcinoma 4T1...
December 29, 2016: Oncotarget
https://www.readbyqxmd.com/read/28038383/co-expression-of-tim-3-and-ceacam1-promotes-t-cell-exhaustion-in-colorectal-cancer-patients
#6
Yang Zhang, Pengcheng Cai, Lei Li, Liang Shi, Panpan Chang, Tao Liang, Qianqian Yang, Yang Liu, Lin Wang, Lihua Hu
T-cell immunoglobulin domain and mucin domain-3(TIM-3) is an activation induced inhibitory molecule involved in immune tolerance and is recently reported to induce T cell exhaustion which is mediated by carcinoembryonic antigen cell adhesion molecule 1(CEACAM1), another well-known molecule expressed on activated T cells and involved in T cell inhibition. To investigate the expression of TIM-3 and CEACAM1 on circulating CD8(+) T cells and tumor infiltrating lymphocytes (TILs), 65 diagnosed colorectal cancer (CRC) patients and 38 healthy controls were enrolled in this study and the results showed that TIM-3 and CEACAM1 were both highly expressed on circulating CD8(+) T cells in CRC patients and elevated on TILs compared with paraneoplastic T cells...
December 27, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/28035752/the-effect-of-mhc-antigen-matching-between-donors-and-recipients-on-skin-tolerance-of-vascularized-composite-allografts
#7
K Shanmugarajah, H Powell, D A Leonard, C Mallard, A Albritton, E Harrington, M A Randolph, E Farkash, D H Sachs, J M Kurtz, C L Cetrulo
The emergence of skin-containing vascularized composite allografts (VCAs) has provided impetus to understand factors affecting rejection/tolerance of skin. VCA tolerance can be established in miniature swine across haploidentical MHC barriers using mixed chimerism. As the deceased donor pool for VCAs does not permit MHC antigen matching, clinical VCAs are transplanted across varying MHC disparities. Here, we investigated whether sharing of MHC class I or class II antigens between donors and recipients influences VCA skin tolerance...
December 30, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28011931/htlv-1-tax-specific-ctl-epitope-pulsed-dendritic-cell-therapy-reduces-proviral-load-in-infected-rats-with-immune-tolerance-against-tax
#8
Satomi Ando, Atsuhiko Hasegawa, Yuji Murakami, Na Zeng, Natsuko Takatsuka, Yasuhiro Maeda, Takao Masuda, Youko Suehiro, Mari Kannagi
Adult T cell leukemia/lymphoma (ATL), a CD4(+) T cell malignancy with a poor prognosis, is caused by human T cell leukemia virus type 1 (HTLV-1) infection. High proviral load (PVL) is a risk factor for the progression to ATL. We previously reported that some asymptomatic carriers had severely reduced functions of CTLs against HTLV-1 Tax, the major target Ag. Furthermore, the CTL responses tended to be inversely correlated with PVL, suggesting that weak HTLV-1-specific CTL responses may be involved in the elevation of PVL...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28009481/renal-allograft-survival-in-nonhuman-primates-infused-with-donor-antigen-pulsed-autologous-regulatory-dendritic-cells
#9
M B Ezzelarab, D Raich-Regue, L Lu, A F Zahorchak, A Perez-Gutierrez, A Humar, M Wijkstrom, M Minervini, R W Wiseman, D K C Cooper, A E Morelli, A W Thomson
Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg pre-loaded with cell membrane vesicles from allogeneic PBMC, induce T cell hyporesponsiveness to donor alloAg in vitro. These donor alloAg-pulsed autologous DCreg (1.4-3.6 x 10(6) /kg) were administered intravenously, one day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 [CTLA4] Ig) and tapered rapamycin...
December 23, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28008595/defective-expression-of-apoptosis-related-molecules-in-multiple-sclerosis-patients-is-normalized-early-after-autologous-haematopoietic-stem-cell-transplantation
#10
G L V de Oliveira, A F Ferreira, E P L Gasparotto, S Kashima, D T Covas, C T Guerreiro, D G Brum, A A Barreira, J C Voltarelli, B P Simões, M C Oliveira, F A de Castro, K C R Malmegrim
Defective apoptosis might be involved in the pathogenesis of multiple sclerosis (MS). We evaluated apoptosis-related molecules in MS patients before and after autologous haematopoietic stem cell transplantation (AHSCT) using BCNU, Etoposide, AraC and Melphalan (BEAM) or cyclophosphamide (CY)-based conditioning regimens. Patients were followed for clinical and immunological parameters for 2 years after AHSCT. At baseline, MS patients had decreased proapoptotic BAD, BAX and FASL and increased A1 gene expression when compared with healthy counterparts...
November 7, 2016: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/27990287/coeliac-disease-a-unique-model-for-investigating-broken-tolerance-in-autoimmunity
#11
REVIEW
Melinda Y Hardy, Jason A Tye-Din
Coeliac disease, a prevalent immune-mediated enteropathy driven by dietary gluten, provides an exceptional human model to dissect the genetic, environmental and immunologic factors operating in autoimmunity. Despite the causative antigen being an exogenous food protein, coeliac disease has many features in common with autoimmune disease including a strong HLA class II association and the presence of pathogenic CD4(+) T cells and autoantibodies. CD8(+) intraepithelial lymphocytes specifically target and destroy intestinal epithelium in response to stress signals and not a specific antigen...
November 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27974398/safety-and-immunogenicity-of-the-recombinant-bcg-vaccine-vpm1002-in-hiv-unexposed-newborn-infants-in-south-africa
#12
André G Loxton, Julia K Knaul, Leander Grode, Andrea Gutschmidt, Christiane Meller, Bernd Eisele, Hilary Johnstone, Gian van der Spuy, Jeroen Maertzdorf, Stefan H E Kaufmann, Anneke C Hesseling, Gerhard Walzl, Mark F Cotton
BACKGROUND: Tuberculosis is a global threat to which infants are especially vulnerable. Effective vaccines are required to protect infants from this devastating disease. VPM1002, a novel recombinant Bacille Calmette-Guérin (BCG) vaccine, previously shown to be safe and immunogenic in adults, was evaluated for safety in its intended target population, namely newborn infants in a region with high prevalence of tuberculosis. METHODS: A total of forty-eight newborns were vaccinated intradermally with VPM1002 (n=36) or BCG Danish strain (n=12) in a Phase II open-labelled, randomized trial with a 6 month follow-up period...
December 14, 2016: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/27965674/molecular-and-cellular-characterization-of-human-cd8-t-suppressor-cells
#13
REVIEW
Zheng Xu, Sophey Ho, Chih-Chao Chang, Qing-Yin Zhang, Elena-Rodica Vasilescu, George Vlad, Nicole Suciu-Foca
Bidirectional interactions between dendritic cells and Ag-experienced T cells initiate either a tolerogenic or immunogenic pathway. The outcome of these interactions is of crucial importance in malignancy, transplantation, and autoimmune diseases. Blockade of costimulation results in the induction of T helper cell anergy and subsequent differentiation of antigen-specific CD8(+) T suppressor/regulatory cells (Ts). Ts, primed in the presence of inhibitory signals, exert their inhibitory function in an antigen-specific manner, a feature with tremendous clinical potential...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27941004/optimization-of-peptide-vaccines-to-induce-robust-antitumor-cd4-t-cell-responses
#14
Takumi Kumai, Sujin Lee, Hyun-Il Cho, Hussein Sultan, Hiroya Kobayashi, Yasuaki Harabuchi, Esteban Celis
Substantial evidence indicates that immunotherapy is a feasible and effective approach for the treatment of numerous types of cancer. Among various immunotherapy options, peptide vaccines to generate antitumor T cells appear as promising candidates, because of their cost effectiveness and ease of implementation. Nevertheless, most peptide vaccines are notorious for being weekly immunogenic and, thus, optimization of the vaccination strategy is essential to achieve therapeutic effectiveness. In addition, effective peptide vaccines must stimulate both CD8 cytotoxic and CD4 helper T lymphocytes...
January 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/27933315/immunogenicity-of-self-tumor-associated-proteins-is-enhanced-through-protein-truncation
#15
Tim Kottke, Kevin G Shim, Vanesa Alonso-Camino, Shane Zaidi, Rosa Maria Diaz, Jose Pulido, Jill Thompson, Karishma R Rajani, Laura Evgin, Elizabeth Ilett, Hardev Pandha, Kevin Harrington, Peter Selby, Alan Melcher, Richard Vile
We showed previously that therapy with Vesicular Stomatitis Virus (VSV) expressing tumor-associated proteins eradicates established tumors. We show here that when cellular cDNA were cloned into VSV which retained their own poly-A signal, viral species emerged in culture which had deleted the cellular poly-A signal and also contained a truncated form of the protein coding sequence. Typically, the truncation occurred such that a Tyrosine-encoding codon was converted into a STOP codon. We believe that the truncation of tumor-associated proteins expressed from VSV in this way occurred to preserve the ability of the virus to replicate efficiently...
2016: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/27925187/depletion-of-cd52-positive-cells-inhibits-the-development-of-central-nervous-system-autoimmune-disease-but-deletes-an-immune-tolerance-promoting-cd8-t-cell-population-implications-for-secondary-autoimmunity-of-alemtuzumab-in-multiple-sclerosis
#16
Stephanie von Kutzleben, Gareth Pryce, Gavin Giovannoni, David Baker
The objective was to determine whether CD52 lymphocyte depletion can act to promote immunological tolerance induction by way of intravenous antigen administration such that it could be used to either improve efficiency of multiple sclerosis (MS) inhibition or inhibit secondary autoimmunities that may occur following alemtuzumab use in MS. Relapsing experimental autoimmune encephalomyelitis was induced in ABH mice and immune cell depletion was therapeutically applied using mouse CD52 or CD4 (in conjunction with CD8 or CD20) depleting monoclonal antibodies...
December 7, 2016: Immunology
https://www.readbyqxmd.com/read/27922687/immature-myeloid-derived-suppressor-cells-a-bridge-between-inflammation-and-cancer-review
#17
Caterina Musolino, Alessandro Allegra, Govanni Pioggia, Sebastiano Gangemi
Chronic inflammation is considered to be one of the hallmarks of tumor initiation and progression. Changes occurring in the microenvironment of progressing tumors resemble the process of chronic inflammation, which begins with ischemia followed by interstitial and cellular edema, appearance of immune cells, growth of blood vessels and tissue repair, and development of inflammatory infiltrates. Moreover, long‑term production and accumulation of inflammatory factors lead to local and systemic immunosuppression associated with cancer progression...
December 5, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27920091/interferon-gamma-limits-diabetogenic-cd8-t-cell-effector-responses-in-type-1-diabetes
#18
John P Driver, Jeremy J Racine, Cheng Ye, Deanna J Lamont, Brittney N Newby, Caroline G McPhee-Leeth, Harold D Chapman, Todd M Brusko, Yi-Guang Chen, Clayton E Mathews, David V Serreze
Type 1 diabetes development in the NOD mouse model is widely reported to be dependent on high-level production by autoreactive CD4(+) and CD8(+) T-cells of IFNγ, generally considered a pro-inflammatory cytokine. However, IFNγ can also participate in tolerance induction pathways, indicating it is not solely pro-inflammatory. This study addresses how IFNγ can suppress activation of diabetogenic CD8(+) T-cells. CD8(+) T-cells transgenically expressing the diabetogenic AI4 T-cell receptor (TCR) adoptively transferred disease to otherwise unmanipulated NOD...
December 5, 2016: Diabetes
https://www.readbyqxmd.com/read/27919957/simultaneous-administration-of-statins-and-pioglitazone-limits-tumor-growth-in-a-rat-model-of-malignant-glioma
#19
Jorge Humberto Tapia-Pérez, Robert Preininger, Elmar Kirches, Annegret Reinhold, Jana Butzmann, Sylvia Prilloff, Christian Mawrin, Thomas Schneider
BACKGROUND/AIM: Statins are cholesterol reducers with considerable dose-dependent effect against glioma cells. The apoptotic effect could be increased by combining statins or by adding pioglitazone (PGZ). The last one is an anti-diabetic drug, an agonist of the peroxisome proliferator-activated receptor-gamma (PPARG). We used an animal model to test the effect of such combination in vivo and we investigated the changes on immunological processes. MATERIALS AND METHODS: Thirty-three rats (F344/DuCrl) were anesthetized and glioblastoma (F98) cells were implanted stereotactically...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27914923/alloantigen-gene-transfer-to-hepatocytes-promotes-tolerance-to-pancreatic-islet-graft-by-inducing-cd8-regulatory-t-cells
#20
Valentin Le Guen, Jean-Paul Judor, Françoise Boeffard, Vanessa Gauttier, Nicolas Ferry, Jean-Paul Soulillou, Sophie Brouard, Sophie Conchon
BACKGROUND & AIM: Induction of donor-specific immune tolerance is a good alternative to chronic life-long immunosuppression for transplant patients. Donor major histocompatibility complex (MHC) molecules represent the main targets of the allogeneic immune response of transplant recipients. Liver-targeted gene transfer with viral vectors induces tolerance toward the encoded antigen. The aim of this work was to determine whether alloantigen gene transfer to hepatocytes induces tolerance and promotes graft acceptance...
November 30, 2016: Journal of Hepatology
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