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CD8 memory

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https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#1
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28212742/demonstration-of-tissue-resident-memory-cd8-t-cells-in-insulitic-lesions-in-adult-patients-with-recent-onset-type-1-diabetes
#2
Enida Kuric, Peter Seiron, Lars Krogvold, Bjørn Edwin, Trond Buanes, Kristian F Hanssen, Oskar Skog, Knut Dahl-Jørgensen, Olle Korsgren
Subtypes of CD8(+) T cells in insulitic lesions in biopsy specimens from six subjects with recent-onset type 1 diabetes (T1D) and six nondiabetic matched controls were analyzed using simultaneous multicolor immunofluorescence. Also, insulitic islets based on accumulation of CD3(+) T cells were microdissected with laser-capture microscopy, and gene transcripts associated with inflammation and autoimmunity were analyzed. We found a substantial proportion, 43%, of the CD8(+) T cells in the insulitic lesions to display a tissue resident memory T cell (TRM) (CD8(+)CD69(+)CD103(+)) phenotype in T1D subjects...
March 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28205361/immunotherapy-against-metastatic-bladder-cancer-by-combined-administration-of-granulocyte-macrophage-colony-stimulating-factor-and-interleukin-2-surface-modified-mb49-bladder-cancer-stem-cells-vaccine
#3
Chun-Yan Wang, Rui Hua, Li Liu, Xiaomin Zhan, Simei Chen, Song Quan, Qing-Jun Chu, Yong-Tong Zhu
In previous studies, it has been shown that the granulocyte macrophage-colony stimulating factor (GM-CSF) or interleukin-2 (IL-2) surface modified MB49 bladder cancer stem cells (MCSCs) vaccine could induce a specific antitumor immunity and against bladder cancer in mice model respectively. However, whether combined administration of GM-CSF and IL-2 could produce specific immune responses to cancer stem cells (CSCs) was uncertain. MCSCs were established and characterized. GM-CSF and IL-2 MCSCs vaccines were prepared and bioactivity was evaluated...
February 16, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28202771/delayed-differentiation-of-potent-effector-cd8-t-cells-reducing-viremia-and-reservoir-seeding-in-acute-hiv-infection
#4
Hiroshi Takata, Supranee Buranapraditkun, Cari Kessing, James L K Fletcher, Roshell Muir, Virginie Tardif, Pearline Cartwright, Claire Vandergeeten, Wendy Bakeman, Carmen N Nichols, Suteeraporn Pinyakorn, Pokrath Hansasuta, Eugene Kroon, Thep Chalermchai, Robert O'Connell, Jerome Kim, Nittaya Phanuphak, Merlin L Robb, Nelson L Michael, Nicolas Chomont, Elias K Haddad, Jintanat Ananworanich, Lydie Trautmann
CD8(+) T cells play a critical role in controlling HIV viremia and could be important in reducing HIV-infected cells in approaches to eradicate HIV. The simian immunodeficiency virus model provided the proof of concept for a CD8(+) T cell-mediated reservoir clearance but showed conflicting evidence on the role of these cells to eliminate HIV-infected cells. In humans, HIV-specific CD8(+) T cell responses have not been associated with a reduction of the HIV-infected cell pool in vivo. We studied HIV-specific CD8(+) T cells in the RV254 cohort of individuals initiating ART in the earliest stages of acute HIV infection (AHI)...
February 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28199780/cytomegalovirus-responsive-cd8-t-cells-expand-after-solid-organ-transplantation-in-the-absence-of-cmv-disease
#5
Lauren E Higdon, Jennifer Trofe-Clark, Sai Liu, Kenneth B Margulies, Malaya K Sahoo, Emily Blumberg, Benjamin A Pinsky, Jonathan S Maltzman
Cytomegalovirus (CMV) is a major cause of morbidity and mortality in solid-organ transplant recipients. Approximately 60% of adults are CMV seropositive indicating previous exposure. Following resolution of primary infection, CMV remains in a latent state. Reactivation is controlled by memory T cells in healthy individuals; transplant recipients have reduced memory T cell function due to chronic immunosuppressive therapies. In this study, CD8(+) T cell responses to CMV polypeptides IE-1 and pp65 were analyzed in sixteen CMV seropositive renal and cardiac transplant recipients longitudinally pre- and post-transplant...
February 15, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28198545/the-therapeutic-t-cell-response-induced-by-tumor-delivery-of-tnf-and-melphalan-is-dependent-on-early-triggering-of-natural-killer-and-dendritic-cells
#6
Enrica Balza, Silvia Zanellato, Alessandro Poggi, Daniele Reverberi, Anna Rubartelli, Lorenzo Mortara
The fusion protein L19mTNF (mouse TNF and human antibody fragment L19 directed to fibronectin extra domain-B) selectively targets the tumor vasculature, and in combination with melphalan induces a long-lasting T-cell therapeutic response and immune memory in murine models. Increasing evidence suggests that natural killer (NK) cells act to promote effective T-cell-based antitumor responses. We have analyzed the role of NK cells and dendritic cells (DCs) on two different murine tumor models: WEHI-164 fibrosarcoma and C51 colon carcinoma, in which the combined treatment induces high and low rejection rates respectively...
February 15, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28198539/cytomegalovirus-infection-alters-phenotypes-of-different-%C3%AE-%C3%AE-t-cell-subsets-in-renal-transplant-recipients-with-long-term-stable-graft-function
#7
Silvia Lee, Jacquita S Affandi, Ashley B Irish, Patricia Price
Cytomegalovirus (CMV) infection alters the phenotypic profiles of T-cells and NK cells in healthy and immunocompromised individuals. Here, we examined the effects of CMV infection on the phenotype and functions of γδ T-cell subsets in renal transplant recipients (RTR) stable several years after transplantation (n = 80) and healthy controls (n = 72). Differentiation status, function, and expression of HLA-DR, CD57 and LIR-1 on Vδ2- and Vδ2+ γδ T-cells were examined in peripheral blood cells using flow cytometry...
February 15, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28198363/gut-memories-do-not-fade-epigenetic-regulation-of-lasting-gut-homing-receptor-expression-in-cd4-memory-t-cells
#8
B A Szilagyi, J Triebus, C Kressler, M de Almeida, S Tierling, P Durek, M Mardahl, A Szilagyi, S Floess, J Huehn, U Syrbe, J Walter, J K Polansky, A Hamann
The concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α4β7 was found in CD8(+) T cells, questioning the concept. We now demonstrate that α4β7 expression in murine CD4(+) memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28197388/inhibition-of-tumor-growth-and-metastasis-by-emmprin-multiple-antigenic-peptide-map-vaccination-is-mediated-by-immune-modulation
#9
Elina Simanovich, Vera Brod, Maya M Rahat, Ella Drazdov, Miriam Walter, Jivan Shakya, Michal A Rahat
Previously, we have identified a new epitope in EMMPRIN, a multifunctional protein that mediates tumor cell-macrophage interactions and induces both MMP-9 and VEGF. Here, we synthesized this epitope as an octa-branched multiple antigenic peptide (MAP) to vaccinate mice implanted with subcutaneous syngeneic colon (CT26), prostate (TRAMP-C2) or renal (RENCA) cell line carcinomas. Vaccination inhibited, and sometimes regressed, tumor growth in a dose-dependent manner, reaching 94%, 71% and 72% inhibition, respectively, at a 50 μg dose (p < 0...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197381/immunological-mechanisms-of-intravesical-chitosan-interleukin-12-immunotherapy-against-murine-bladder-cancer
#10
Sean G Smith, John L Baltz, Bhanu Prasanth Koppolu, Sruthi Ravindranathan, Khue Nguyen, David A Zaharoff
There is a critical unmet clinical need for bladder cancer immunotherapies capable of inducing durable antitumor immunity. We have shown that four intravesical treatments with a simple co-formulation of interleukin-12 and the biopolymer chitosan not only destroy orthotopic bladder tumors, but also promote a potent long-lasting systemic immune response as evidenced through tumor-specific in vitro killing assays, complete protection from rechallenge, and abscopal antitumor responses at distant non-treated tumors...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28196735/gtl001-and-bivalent-cyaa-based-therapeutic-vaccine-strategies-against-human-papillomavirus-and-other-tumor-associated-antigens-induce-effector-and-memory-t-cell-responses-that-inhibit-tumor-growth
#11
Michaël Esquerré, Marie Momot, Anne Goubier, Christophe Gonindard, Stéphane Leung-Theung-Long, Yolande Misseri, Marie-Christine Bissery
GTL001 is a bivalent therapeutic vaccine containing human papillomavirus (HPV) 16 and HPV18 E7 proteins inserted in the Bordetella pertussis adenylate cyclase (CyaA) vector intended to prevent cervical cancer in HPV-infected women with normal cervical cytology or mild abnormalities. To be effective, therapeutic cervical cancer vaccines should induce both a T cell-mediated effector response against HPV-infected cells and a robust CD8(+) T-cell memory response to prevent potential later infection. We examined the ability of GTL001 and related bivalent CyaA-based vaccines to induce, in parallel, effector and memory CD8(+) T-cell responses to both vaccine antigens...
February 10, 2017: Vaccine
https://www.readbyqxmd.com/read/28194440/transient-antibody-targeting-of-cd45rc-induces-transplant-tolerance-and-potent-antigen-specific-regulatory-t-cells
#12
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/28193872/nf%C3%AE%C2%BAb-pim-1-eomesodermin-axis-is-critical-for-maintaining-cd8-t-cell-memory-quality
#13
Karin M Knudson, Curtis J Pritzl, Vikas Saxena, Amnon Altman, Mark A Daniels, Emma Teixeiro
T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28191007/antigen-exposure-history-defines-cd8-t-cell-dynamics-and-protection-during-localized-pulmonary-infections
#14
Natalija Van Braeckel-Budimir, Matthew D Martin, Stacey M Hartwig, Kevin L Legge, Vladimir P Badovinac, John T Harty
Unlike systemic infections, little is known about the role of repeated localized infections on (re)shaping pathogen-specific memory CD8 T cell responses. Here, we used primary (1°) and secondary (2°) intranasal influenza virus infections of mice as a model to study intrinsic memory CD8 T cell properties. We show that secondary antigen exposure, relative to a single infection, generates memory CD8 T cell responses of superior magnitude in multiple tissue compartments including blood, spleen, draining lymph nodes, and lung...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28182750/chemoprophylaxis-with-sporozoite-immunization-in-p-knowlesi-rhesus-monkeys-confers-protection-and-elicits-sporozoite-specific-memory-t-cells-in-the-liver
#15
Sathit Pichyangkul, Michele D Spring, Kosol Yongvanitchit, Utaiwan Kum-Arb, Amporn Limsalakpetch, Rawiwan Im-Erbsin, Ratawan Ubalee, Pattaraporn Vanachayangkul, Edmond J Remarque, Evelina Angov, Philip L Smith, David L Saunders
Whole malaria sporozoite vaccine regimens are promising new strategies, and some candidates have demonstrated high rates of durable clinical protection associated with memory T cell responses. Little is known about the anatomical distribution of memory T cells following whole sporozoite vaccines, and immunization of nonhuman primates can be used as a relevant model for humans. We conducted a chemoprophylaxis with sporozoite (CPS) immunization in P. knowlesi rhesus monkeys and challenged via mosquito bites. Half of CPS immunized animals developed complete protection, with a marked delay in parasitemia demonstrated in the other half...
2017: PloS One
https://www.readbyqxmd.com/read/28179523/progesterone-based-contraceptives-reduce-adaptive-immune-responses-and-protection-against-sequential-influenza-a-virus-infections
#16
Olivia J Hall, Raffael Nachbagauer, Meghan S Vermillion, Ashley L Fink, Vanessa Phuong, Florian Krammer, Sabra L Klein
In addition to their intended use, progesterone (P4)-based contraceptives promote anti-inflammatory immune responses, yet their effects on the outcome of infectious diseases, including influenza A virus (IAV), are rarely evaluated. To evaluate their impact on immune responses to sequential IAV infections, adult female mice were treated with placebo or one of two progestins, P4 or levonorgestrel (LNG), and infected with mouse adapted (ma) H1N1 virus. Treatment with P4 or LNG reduced morbidity, but had no effect on pulmonary virus titers, during primary H1N1 infection as compared to placebo treatment...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28179496/cutting-edge-chromatin-accessibility-programs-cd8-t-cell-memory
#17
Christopher D Scharer, Alexander P R Bally, Bhanu Gandham, Jeremy M Boss
CD8 T cell memory is characterized by rapid recall of effector function, increased proliferation, and reduced activation requirements. Despite the extensive functional characterization, the molecular mechanisms that facilitate these enhanced properties are not well characterized. In this study, the assay for transposase-accessible chromatin sequencing was employed to map the cis-regulatory elements in CD8 T cells responding to acute and chronic lymphocytic choriomeningitis virus infections. Integration of chromatin accessibility profiles with gene expression data identified unique regulatory modules that were enriched for distinct combinations of transcription factor-binding motifs...
February 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28167454/peripheral-cd8-effector-memory-type-1-t-cells-correlate-with-outcome-in-ipilimumab-treated-stage-iv-melanoma-patients
#18
Kilian Wistuba-Hamprecht, Alexander Martens, Florian Heubach, Emanuela Romano, Marnix Geukes Foppen, Jianda Yuan, Michael Postow, Phillip Wong, Domenico Mallardo, Bastian Schilling, Anna Maria Di Giacomo, Amir Khammari, Brigitte Dreno, Michele Maio, Dirk Schadendorf, Paolo A Ascierto, Jedd D Wolchok, Christian U Blank, Claus Garbe, Graham Pawelec, Benjamin Weide
The role of the assessment of peripheral T-cell phenotypes in predicting overall survival (OS) after ipilimumab treatment is unclear. Here, we analysed mononuclear cells in the blood before and at different time points during treatment with ipilimumab in 137 late-stage melanoma patients. The proportions of baseline naïve and memory T-cells were measured by flow cytometry and correlated with OS, with an emphasis on PD-1 expression. High frequencies (>13%) of CD8 effector-memory type 1 (EM1) T-cells at baseline correlated with longer OS (p = 0...
March 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28164171/diminished-cd103-%C3%AE-e%C3%AE-7-expression-on-resident-t-cells-from-the-female-genital-tract-of-hiv-positive-women
#19
David C Moylan, Paul A Goepfert, Mirjam-Colette Kempf, Michael S Saag, Holly E Richter, Jiri Mestecky, Steffanie Sabbaj
BACKGROUND: Tissue resident memory T cells (TrM) provide an enhanced response against infection at mucosal surfaces, yet their function has not been extensively studied in humans, including the female genital tract (FGT). METHODS: Using polychromatic flow cytometry, we studied TrM cells, defined as CD62L-CCR7-CD103(+)CD69(+) CD4(+) and CD8(+) T cells in mucosa-derived T cells from healthy and HIV-positive women. RESULTS: We demonstrate that TrM are present in the FGT of healthy and HIV-positive women...
October 2016: Pathogens & Immunity
https://www.readbyqxmd.com/read/28163249/activation-and-exhaustion-of-antigen-specific-cd8-t-cells-occur-in-different-splenic-compartments-during-infection-with-plasmodium-berghei
#20
Ganchimeg Bayarsaikhan, Mana Miyakoda, Kazuo Yamamoto, Daisuke Kimura, Masoud Akbari, Masao Yuda, Katsuyuki Yui
The spleen is the major organ in which T cells are primed during infection with malaria parasites. However, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. We examined murine CD8(+) T cell responses during infection with Plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (OVA) protein and compared the responses with those elicited by Listeria monocytogenes expressing the same antigen. OVA-specific CD8(+) T cells were mainly activated in the white pulp of the spleen during malaria infection, as similarly observed during Listeria infection...
February 3, 2017: Parasitology International
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