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CD8 memory

Weiping Cao, Margarita Mishina, Samuel Amoah, Wadzanai P Mboko, Caitlin Bohannon, James McCoy, Suresh K Mittal, Shivaprakash Gangappa, Suryaprakash Sambhara
Avian influenza virus infection is a serious public health threat and preventive vaccination is the most cost-effective public health intervention strategy. Unfortunately, currently available unadjuvanted avian influenza vaccines are poorly immunogenic and alternative vaccine formulations and delivery strategies are in urgent need to reduce the high risk of avian influenza pandemics. Cationic polymers have been widely used as vectors for gene delivery in vitro and in vivo. In this study, we formulated H5N1 influenza vaccines with GenJet™ or in vivo-jetPEI® , and showed that these formulations significantly enhanced the immunogenicity of H5N1 vaccines and conferred protective immunity in a mouse model...
November 2018: Drug Delivery
Monica Vaccari, Genoveffa Franchini
Germinal centers (GCs) are organized lymphoid tissue microstructures where B cells proliferate and differentiate into memory B cells and plasma cells. A few distinctive subsets of highly specialized T cells gain access to the GCs by expressing the B cell zone-homing C-X-C chemokine receptor type 5 (CXCR5) while losing the T cell zone-homing chemokine receptor CCR7. Help from T cells is critical to induce B cell proliferation and somatic hyper mutation and to limit GC reactions. CD4+ T follicular helper (TFH ) cells required for the formation of GCs and for the generation of long-lived, high-affinity B cells...
2018: Frontiers in Immunology
Franklin R Toapanta, Paula J Bernal, Karen L Kotloff, Myron M Levine, Marcelo B Sztein
BACKGROUND: Shigellosis persists as a public health problem worldwide causing ~ 165,000 deaths every year, of which ~ 55,000 are in children less than 5 years of age. No vaccine against shigellosis is currently licensed. The live-attenuated Shigella flexneri 2a vaccine candidate CVD 1208S (S. flexneri 2a; ΔguaBA, Δset, Δsen) demonstrated to be safe and immunogenic in phase 1 and 2 clinical trials. Earlier reports focused on humoral immunity. However, Shigella is an intracellular pathogen and therefore, T cell mediated immunity (T-CMI) is also expected to play an important role...
March 13, 2018: Journal of Translational Medicine
Brittany P Lassiter, Siqi Guo, Stephen J Beebe
Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver...
March 13, 2018: Cancers
Jie Wang, Lina Yang, Xiaohe Mao, Zaiye Li, Xiaoyu Lin, Canhua Jiang
It has been shown that the peripheral blood mononuclear cells (PBMCs) from oral squamous cell carcinoma (OSCC) patients presented cytotoxic CD8 T cell response against Streptococcus salivarius (S. salivarius), of which the frequency was positively associated with recurrence-free survival in OSCC patients. To identify the conditions required for regulating S. salivarius-specific CD8 T cell-mediated cytotoxicity, we selectively depleted individual components of the PBMCs, and observed that the depletion of monocytes/macrophages, but not other immune cell subsets, significantly downregulated the S...
March 9, 2018: Experimental Cell Research
John Joseph Heath, Neva Jennifer Fudge, Maureen Elizabeth Gallant, Michael David Grant
Antiretroviral therapy (ART) effectively extends the life expectancy of human immunodeficiency virus (HIV)-infected individuals; however, age-related morbidities have emerged as major clinical concerns. In this context, coinfection with cytomegalovirus (CMV) accelerates immune senescence and elevates risk for other age-related morbidities, possibly through increased inflammation. We investigated potential relationships between CMV memory inflation, immune senescence, and inflammation by measuring markers of inflammation and telomere lengths of different lymphocyte subsets in HIV-infected individuals seropositive for anti-CMV antibodies...
2018: Frontiers in Immunology
Maile K Hollinger, Valentina Giudice, Nicole A Cummings, Guillermo Rivell, Hansheng Zhang, Sachiko Kajigaya, Keyvan Keyvanfar, Jichun Chen, Xingmin Feng, Neal S Young
While PD-1 blockade has revolutionized cancer immunotherapy, immune-related adverse events (irAEs) present life-threatening complications. Recent reports of aplastic anemia (AA) as irAEs implicate PD-1/PD-L1 as important in preventing immune-mediated destruction of the hematopoietic niche. Infusion of PD-1-deficient (PD-1 KO) lymph node (LN) cells into minor-antigen mismatched mice resulted in early mortality, as well as more severe BM hypoplasia, anemia, and BM microarchitecture disruption in PD-1 KO LN-infused mice relative to mice that received B6 LN cell infusion...
March 7, 2018: Experimental Hematology
Glenn R Bantug, Marco Fischer, Jasmin Grählert, Maria L Balmer, Gunhild Unterstab, Leyla Develioglu, Rebekah Steiner, Lianjun Zhang, Ana S H Costa, Patrick M Gubser, Anne-Valérie Burgener, Ursula Sauder, Jordan Löliger, Réka Belle, Sarah Dimeloe, Jonas Lötscher, Annaïse Jauch, Mike Recher, Gideon Hönger, Michael N Hall, Pedro Romero, Christian Frezza, Christoph Hess
Glycolysis is linked to the rapid response of memory CD8+ T cells, but the molecular and subcellular structural elements enabling enhanced glucose metabolism in nascent activated memory CD8+ T cells are unknown. We found that rapid activation of protein kinase B (PKB or AKT) by mammalian target of rapamycin complex 2 (mTORC2) led to inhibition of glycogen synthase kinase 3β (GSK3β) at mitochondria-endoplasmic reticulum (ER) junctions. This enabled recruitment of hexokinase I (HK-I) to the voltage-dependent anion channel (VDAC) on mitochondria...
March 1, 2018: Immunity
Kent J Weinhold, Jack F Bukowski, Todd V Brennan, Robert J Noveck, Janet S Staats, Liwen Lin, Linda Stempora, Constance Hammond, Ann Wouters, Christopher F Mojcik, John Cheng, Mark Collinge, Michael I Jesson, Anasuya Hazra, Pinaki Biswas, Shuping Lan, James D Clark, Jennifer A Hodge
This study evaluated the short-term effects of tofacitinib treatment on peripheral blood leukocyte phenotype and function, and the reversibility of any such effects following treatment withdrawal in healthy volunteers. Cytomegalovirus (CMV)-seropositive subjects received oral tofacitinib 10 mg twice daily for 4 weeks and were followed for 4 weeks after drug withdrawal. There were slight increases in total lymphocyte and total T-cell counts during tofacitinib treatment, and B-cell counts increased by up to 26%...
March 5, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Peter Hart, Alastair Copland, Gil Reynolds Diogo, Shane Harris, Ralf Spallek, Wulf Oehlmann, Mahavir Singh, Juan Basile, Martin Rottenberg, Matthew John Paul, Rajko Reljic
Tuberculosis (TB) is the leading cause of death from infectious disease, and the current vaccine, Bacillus Calmette-Guerin (BCG), is inadequate. Nanoparticles (NPs) are an emerging vaccine technology, with recent successes in oncology and infectious diseases. NPs have been exploited as antigen delivery systems and also for their adjuvantic properties. However, the mechanisms underlying their immunological activity remain obscure. Here, we developed a novel mucosal TB vaccine (Nano-FP1) based upon yellow carnauba wax NPs (YC-NPs), coated with a fusion protein consisting of three Mycobacterium tuberculosis (Mtb) antigens: Acr, Ag85B, and HBHA...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Chien-Chia Chen, Alice Koenig, Carole Saison, Suzan Dahdal, Guillaume Rigault, Thomas Barba, Morgan Taillardet, Dimitri Chartoire, Michel Ovize, Emmanuel Morelon, Thierry Defrance, Olivier Thaunat
Antibody-mediated rejection is currently the leading cause of transplant failure. Prevailing dogma predicts that B cells differentiate into anti-donor-specific antibody (DSA)-producing plasma cells only with the help of CD4+ T cells. Yet, previous studies have shown that dependence on helper T cells decreases when high amounts of protein antigen are recruited to the spleen, two conditions potentially met by organ transplantation. This could explain why a significant proportion of transplant recipients develop DSA despite therapeutic immunosuppression...
2018: Frontiers in Immunology
Pritesh Desai, Vikas Tahiliani, Tarun E Hutchinson, Farhad Dastmalchi, Jessica Stanfield, Georges Abboud, Paul G Thomas, Carl F Ware, Jianxun Song, Michael Croft, Shahram Salek-Ardakani
The transition of effector T cells or memory precursors into distinct long-lived memory T cell subsets is not well understood. Although many molecules made by APCs can contribute to clonal expansion and effector cell differentiation, it is not clear if clonal contraction and memory development is passive or active. Using respiratory virus infection, we found that CD8 T cells that cannot express the TNF family molecule lymphotoxin-like, exhibits i nducible expression, competes with HSV g lycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes (LIGHT) are unimpaired in their initial response and clonally expand to form effector cell pools...
March 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Renan Aguilar-Valenzuela, Jason Netland, Young-Jin Seo, Michael J Bevan, Arash Grakoui, Mehul S Suthar
The mouse model of West Nile virus, which is a leading cause of mosquito-borne encephalitis worldwide, has provided fundamental insights into the host and viral factors that regulate viral pathogenesis and infection outcome. In particular, CD8+ T cells are critical for controlling WNV replication and promoting protection against infection. Here, we present the characterization of a T cell receptor (TCR) transgenic mouse with specificity to the immunodominant epitope in the WNV NS4B protein (herein referred to as transgenic WNV-I mice)...
March 7, 2018: Journal of Virology
Denis R Beckford Vera, Christof C Smith, Lisa M Bixby, Dylan M Glatt, Stuart S Dunn, Ryoichi Saito, William Y Kim, Jonathan S Serody, Benjamin G Vincent, Matthew C Parrott
The ability to non-invasively monitor tumor-infiltrating T cells in vivo could provide a powerful tool to visualize and quantify tumor immune infiltrates. For non-invasive evaluations in vivo, an anti-CD3 mAb was modified with desferrioxamine (DFO) and radiolabeled with zirconium-89 (Zr-89 or 89Zr). Radiolabeled 89Zr-DFO-anti-CD3 was tested for T cell detection using positron emission tomography (PET) in both healthy mice and mice bearing syngeneic bladder cancer BBN975. In vivo PET/CT and ex vivo biodistribution demonstrated preferential accumulation and visualization of tracer in the spleen, thymus, lymph nodes, and bone marrow...
2018: PloS One
Priyanka B Subrahmanyam, Zhiwan Dong, Daniel Gusenleitner, Anita Giobbie-Hurder, Mariano Severgnini, Jun Zhou, Michael Manos, Lauren M Eastman, Holden T Maecker, F Stephen Hodi
BACKGROUND: While immune checkpoint blockade has greatly improved clinical outcomes in diseases such as melanoma, there remains a need for predictive biomarkers to determine who will likely benefit most from which therapy. To date, most biomarkers of response have been identified in the tumors themselves. Biomarkers that could be assessed from peripheral blood would be even more desirable, because of ease of access and reproducibility of sampling. METHODS: We used mass cytometry (CyTOF) to comprehensively profile peripheral blood of melanoma patients, in order to find predictive biomarkers of response to anti-CTLA-4 or anti-PD-1 therapy...
March 6, 2018: Journal for Immunotherapy of Cancer
Debora Vignali, Elisa Cantarelli, Carlotta Bordignon, Adriana Canu, Antonio Citro, Andrea Annoni, Lorenzo Piemonti, Paolo Monti
Stem memory T cells (Tscm) constitute the earliest developmental stage of memory T cells, displaying stem cell-like properties such as self-renewal capacity. Their superior immune reconstitution potential has sparked interest in cancer immune-therapy, vaccine development and immune reconstitution, whereas their role in autoimmunity is largely unexplored. Here we show that autoreactive CD8+ Tscm specific for β cell antigens GAD65, insulin and IGRP are present in patients with type 1 diabetes (T1D). In vitro, generation of autoreactive Tscm from naïve precursors required the presence of the homeostatic cytokine interleukin-7 (IL-7)...
March 5, 2018: Diabetes
Joo-Young Park, Davinna L Ligons, Jung-Hyun Park
IL-15 is a cytokine of the common γ-chain family that is critical for natural killer (NK), invariant natural killer T ( i NKT), and CD8 memory T cell development and homeostasis. The role of IL-15 in regulating effector T cell subsets, however, remains incompletely understood. IL-15 is mostly expressed by stromal cells, myeloid cells, and dendritic cells (DCs). Whether T cells themselves can express IL-15, and if so, whether such T cell-derived IL-15 could play an autocrine role in T cells are interesting questions that were previously addressed but answered with mixed results...
February 2018: Immune Network
Eleni Panagioti, Paul Klenerman, Lian N Lee, Sjoerd H van der Burg, Ramon Arens
For many years, the focus of prophylactic vaccines was to elicit neutralizing antibodies, but it has become increasingly evident that T cell-mediated immunity plays a central role in controlling persistent viral infections such as with human immunodeficiency virus, cytomegalovirus, and hepatitis C virus. Currently, various promising prophylactic vaccines, capable of inducing substantial vaccine-specific T cell responses, are investigated in preclinical and clinical studies. There is compelling evidence that protection by T cells is related to the magnitude and breadth of the T cell response, the type and homing properties of the memory T cell subsets, and their cytokine polyfunctionality and metabolic fitness...
2018: Frontiers in Immunology
Ilija Brizić, Božo Sušak, Maja Arapović, Peter C Huszthy, Lea Hiršl, Daria Kveštak, Vanda Juranić Lisnić, Mijo Golemac, Ester Pernjak Pugel, Jelena Tomac, Annette Oxenius, William J Britt, Jurica Arapović, Astrid Krmpotić, Stipan Jonjić
Congenital HCMV infection is a leading infectious cause of long-term neurodevelopmental sequelae. Infection of newborn mice with MCMV intraperitoneally is a well-established model of congenital HCMV infection, which best recapitulates the hematogenous route of virus spread to brain and subsequent pathology. Here we used this model to investigate the role, dynamics and phenotype of CD8+ T cells in the brain following infection of newborn mice. We show that CD8+ T cells infiltrate the brain and form a pool of tissue-resident memory T cells (TRM cells) that persist for lifetime...
March 3, 2018: European Journal of Immunology
Aglaia Domouchtsidou, Vahé Barsegian, Stefan P Mueller, Jan Best, Judith Ertle, Sotiria Bedreli, Peter A Horn, Andreas Bockisch, Monika Lindemann
The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays...
March 2, 2018: Cancer Immunology, Immunotherapy: CII
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