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https://www.readbyqxmd.com/read/29790576/memory-t-cell-subsets-in-healthy-gingiva-and-periodontitis-tissues
#1
Rangsini Mahanonda, Chantrakorn Champaiboon, Keskanya Subbalekha, Noppadol Sa-Ard-Iam, Arsarn Yongyuth, Benjarat Isaraphithakkul, Pimprapa Rerkyen, Orawan Charatkulangkun, Sathit Pichyangkul
BACKGROUND: In the gingival sulcus, effective and balanced innate and adaptive immune responses against subgingival plaque microbiome are crucial to maintain immune homeostasis. In this study, we investigated the memory T cell subsets in healthy gingiva and periodontitis tissues. METHODS: Anatomical localization of T cells (CD3+ , CD4+ , and CD8+ ) in healthy gingiva and periodontitis tissues were examined immunohistochemically. Subsets of memory T cells from isolated gingival cells were analyzed by flow cytometry using a cocktail of monoclonal antibodies (anti-CD69, anti-CD103, anti-CD45RA, anti-CCR7, anti-CD28, and anti-CD95)...
May 23, 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29784675/radiation-followed-by-ox40-stimulation-drives-local-and-abscopal-antitumor-effects-in-an-anti-pd1-resistant-lung-tumor-model
#2
Sharareh Niknam, Hampartsoum B Barsoumian, Jonathan E Schoenhals, Heather Jackson, Niranjan Yanamandra, Mauricio S Caetano, Ailin Li, Ahmed I Younes, Alexandra P Cadena, Taylor R Cushman, Joe Y Chang, Quynh Nguyen, Daniel R Gomez, Adi Diab, John V Heymach, Patrick Hwu, Maria Angelica Cortez, James W Welsh
PURPOSE: Radiation is used extensively to treat localized cancer, but improved understanding of its effects on the immune system have increased interest in its potential systemic (abscopal) effects, particularly in combination with checkpoint inhibitors such as anti-PD1. The majority of patients either do not respond or develop resistance to monotherapy over time. Here, we investigated the efficacy of OX40 (CD134) stimulation as an alternative immunotherapeutic approach in combination with radiotherapy (XRT) in a murine model of anti-PD1-resistant lung tumors...
May 21, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29775806/case-report-cd103-cd8-lymphocytes-characterize-the-immune-infiltration-in-a-case-with-pseudoprogression-in-sqnsclc
#3
Pedro Rocha, Max Hardy-Werbin, Dolores Naranjo, Álvaro Taus, Maite Rodrigo, Flavio Zuccarino, René Roth, Oliver Wood, Christian H Ottensmeier, Edurne Arriola
No abstract text is available yet for this article.
May 15, 2018: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29760082/a-cytokine-network-involving-il-36%C3%AE-il-23-and-il-22-promotes-antimicrobial-defense-and-recovery-from-intestinal-barrier-damage
#4
Vu L Ngo, Hirohito Abo, Estera Maxim, Akihito Harusato, Duke Geem, Oscar Medina-Contreras, Didier Merlin, Andrew T Gewirtz, Asma Nusrat, Timothy L Denning
The gut epithelium acts to separate host immune cells from unrestricted interactions with the microbiota and other environmental stimuli. In response to epithelial damage or dysfunction, immune cells are activated to produce interleukin (IL)-22, which is involved in repair and protection of barrier surfaces. However, the specific pathways leading to IL-22 and associated antimicrobial peptide (AMP) production in response to intestinal tissue damage remain incompletely understood. Here, we define a critical IL-36/IL-23/IL-22 cytokine network that is instrumental for AMP production and host defense...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29751114/very-low-numbers-of-cd4-foxp3-tregs-expanded-in-donors-via-tl1a-ig-and-low-dose-il-2-exhibit-a-distinct-activation-functional-profile-and-suppress-gvhd-in-a-pre-clinical-model
#5
Sabrina Copsel, Dietlinde Wolf, Brandon Kale, Henry Barreras, Casey O Lightbourn, Cameron S Bader, W Alperstein, Norman H Altman, Krishna V Komanduri, Robert B Levy
Regulatory T cells (Tregs) are essential for the maintenance of tolerance and immune homeostasis. In allogeneic hematopoietic stem cell transplantation (aHSCT), transfer of appropriate Treg numbers is a promising therapy for the prevention of graft-versus-host disease (GVHD). We have recently reported a novel approach which induces the marked expansion and selective activation of Tregs in vivo by targeting TNF receptor superfamily 25 (TNFRSF25) and CD25. A potential advance to promote clinical application of Treg cells to ameliorate GVHD and other disorders would be the generation of more potent Treg populations...
May 8, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29743613/immune-quiescence-in-the-oral-mucosa-is-maintained-by-a-uniquely-large-population-of-highly-activated-foxp3-regulatory-t-cells
#6
Joo-Young Park, Hyunsoo Chung, Devon T DiPalma, Xuguang Tai, Jung-Hyun Park
The oral mucosa is a critical barrier tissue that protects the oral cavity against invading pathogens and foreign antigens. Interestingly, inflammation in the oral cavity is rarely observed, indicating that overt immune activation in this site is actively suppressed. Whether Foxp3+ Treg cells are involved in controlling immunity of the oral mucosa, however, is not fully understood. Here, we show that the oral mucosa is highly enriched in Foxp3+ Treg cells, and that oral mucosa Treg cells are phenotypically distinct from those of LN or spleen, as they expressed copious amounts of the tissue-retention molecule CD103 and unusually high-levels of CTLA4...
May 9, 2018: Mucosal Immunology
https://www.readbyqxmd.com/read/29742076/update-on-hairy-cell-leukemia
#7
Robert J Kreitman, Evgeny Arons
Hairy cell leukemia (HCL) is a chronic B-cell malignancy with multiple treatment options, including several that are investigational. Patients present with pancytopenia and splenomegaly, owing to the infiltration of leukemic cells expressing CD22, CD25, CD20, CD103, tartrate-resistant acid phosphatase (TRAP), annexin A1 (ANXA1), and the BRAF V600E mutation. A variant lacking CD25, ANXA1, TRAP, and the BRAF V600E mutation, called HCLv, is more aggressive and is classified as a separate disease. A molecularly defined variant expressing unmutated immunoglobulin heavy variable 4-34 (IGHV4-34) is also aggressive, lacks the BRAF V600E mutation, and has a phenotype of HCL or HCLv...
March 2018: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/29735643/flow-cytometry-data-preparation-guidelines-for-improved-automated-phenotypic-analysis
#8
Daniel Jimenez-Carretero, José M Ligos, María Martínez-López, David Sancho, María C Montoya
Advances in flow cytometry (FCM) increasingly demand adoption of computational analysis tools to tackle the ever-growing data dimensionality. In this study, we tested different data input modes to evaluate how cytometry acquisition configuration and data compensation procedures affect the performance of unsupervised phenotyping tools. An analysis workflow was set up and tested for the detection of changes in reference bead subsets and in a rare subpopulation of murine lymph node CD103+ dendritic cells acquired by conventional or spectral cytometry...
May 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29712852/revealing-the-specificity-of-regulatory-t-cells-in-murine-autoimmune-diabetes
#9
Allyson Spence, Whitney Purtha, Janice Tam, Shen Dong, Youmin Kim, Chia-Hsin Ju, Teague Sterling, Maki Nakayama, William H Robinson, Jeffrey A Bluestone, Mark S Anderson, Qizhi Tang
Regulatory T cells (Tregs) control organ-specific autoimmunity in a tissue antigen-specific manner, yet little is known about their specificity in a natural repertoire. In this study, we used the nonobese diabetic (NOD) mouse model of autoimmune diabetes to investigate the antigen specificity of Tregs present in the inflamed tissue, the islets of Langerhans. Compared with Tregs present in spleen and lymph node, Tregs in the islets showed evidence of antigen stimulation that correlated with higher proliferation and expression of activation markers CD103, ICOS, and TIGIT...
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29691251/nfatc1-promotes-anti-tumoral-effector-functions-and-memory-cd8-t-cell-differentiation-during-non-small-cell-lung-cancer-development
#10
Lisanne Heim, Juliane Friedrich, Marina Engelhardt, Denis I Trufa, Carol I Geppert, Ralf Joachim Rieker, Horia Sirbu, Susetta Finotto
Nuclear factor of activated T cells 1 (NFATc1) is a transcription factor activated by T cell receptor (TCR) and Ca2+-signaling that affects T cell activation and effector function. Upon tumor antigen challenge, TCR and calcium-release-activated channels are induced, promoting NFAT dephosphorylation and translocation into the nucleus. In this study, we report a progressive decrease of NFATc1 in lung tumor tissue and in tumor-infiltrating lymphocytes (TIL) of patients suffering from advanced stage non-small cell lung cancer (NSCLC)...
April 24, 2018: Cancer Research
https://www.readbyqxmd.com/read/29686665/cd161-defines-a-functionally-distinct-subset-of-pro-inflammatory-natural-killer-cells
#11
Ayako Kurioka, Cormac Cosgrove, Yannick Simoni, Bonnie van Wilgenburg, Alessandra Geremia, Sophia Björkander, Eva Sverremark-Ekström, Christine Thurnheer, Huldrych F Günthard, Nina Khanna, Lucy Jane Walker, Carolina V Arancibia-Cárcamo, Evan W Newell, Christian B Willberg, Paul Klenerman
CD161 is a C-type lectin-like receptor expressed on the majority of natural killer (NK) cells; however, the significance of CD161 expression on NK cells has not been comprehensively investigated. Recently, we found that CD161 expression identifies a transcriptional and innate functional phenotype that is shared across various T cell populations. Using mass cytometry and microarray experiments, we demonstrate that this functional phenotype extends to NK cells. CD161 marks NK cells that have retained the ability to respond to innate cytokines during their differentiation, and is lost upon cytomegalovirus-induced maturation in both healthy and human immunodeficiency virus (HIV)-infected patients...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29669782/the-respiratory-environment-diverts-the-development-of-antiviral-memory-cd8-t-cells
#12
Hillary L Shane, Katie L Reagin, Kimberly D Klonowski
Our understanding of memory CD8+ T cells has been largely derived from acute, systemic infection models. However, memory CD8+ T cells generated from mucosal infection exhibit unique properties and, following respiratory infection, are not maintained in the lung long term. To better understand how infection route modifies memory differentiation, we compared murine CD8+ T cell responses to a vesicular stomatitis virus (VSV) challenge generated intranasally (i.n.) or i.v. The i.n. infection resulted in greater peak expansion of VSV-specific CD8+ T cells...
April 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29664571/tissue-resident-memory-t-cells-in-tissue-homeostasis-persistent-infection-and-cancer-surveillance
#13
REVIEW
Thomas Gebhardt, Umaimainthan Palendira, David C Tscharke, Sammy Bedoui
A large proportion of memory T cells disseminated throughout the body are non-recirculating cells whose maintenance and function is regulated by tissue-specific environmental cues. These sessile cells are referred to as tissue-resident memory T (TRM ) cells and similar populations of non-recirculating cells also exist among unconventional T cells and innate lymphocyte cells. The pool of TRM cells is highly diverse with respect to anatomical positioning, phenotype, molecular regulation and effector function...
May 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29603342/indeterminate-pediatric-acute-liver-failure-is-uniquely-characterized-by-a-cd103-cd8-t-cell-infiltrate
#14
Catherine A Chapin, Thomas Burn, Tomas Meijome, Kathleen M Loomes, Hector Melin-Aldana, Portia A Kreiger, Peter F Whitington, Edward M Behrens, Estella M Alonso
The cause of pediatric acute liver failure (PALF) is unknown in up to 40% of cases. Evidence suggests aberrant immune system activation may play a role. We hypothesized indeterminate PALF cases would exhibit a unique pattern of hepatic inflammation. This was a retrospective and prospective study of PALF cases due to indeterminate (iPALF), autoimmune hepatitis (AIH), or known diagnosis (dPALF) etiology. Liver tissue sections were stained with immunohistochemical (IHC) markers for cytotoxic T-cells (CD8), perforin, and tissue resident memory T-cells (CD103), and scored as minimal, moderate, or dense...
March 30, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29602245/reactive-glia-promote-development-of-cd103-cd69-cd8-t-cells-through-programmed-cell-death-ligand-1-pd-l1
#15
Sujata Prasad, Shuxian Hu, Wen S Sheng, Priyanka Chauhan, James R Lokensgard
INTRODUCTION: Previous work from our laboratory has demonstrated in vivo persistence of CD103+ CD69+ brain resident memory CD8+ T-cells (bTRM ) following viral infection, and that the PD-1: PD-L1 pathway promotes development of these TRM cells within the brain. Although glial cells express low basal levels of PD-L1, its expression is upregulated upon IFN-γ-treatment, and they have been shown to modulate antiviral T-cell effector responses through the PD-1: PD-L1 pathway. METHODS: We performed flow cytometric analysis of cells from co-cultures of mixed glia and CD8+ T-cells obtained from wild type mice to investigate the role of glial cells in the development of bTRM ...
March 30, 2018: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/29599411/cd103-tumor-resident-cd8-t-cells-are-associated-with-improved-survival-in-immunotherapy-na%C3%A3-ve-melanoma-patients-and-expand-significantly-during-anti-pd-1-treatment
#16
Jarem Edwards, James S Wilmott, Jason Madore, Tuba Nur Gide, Camelia Quek, Annie Tasker, Angela Ferguson, Jinbiao Chen, Rehana Hewavisenti, Peter Hersey, Thomas Gebhardt, Wolfgang Weninger, Warwick J Britton, Robyn P M Saw, John F Thompson, Alexander M Menzies, Georgina V Long, Richard A Scolyer, Umaimainthan Palendira
Purpose: Therapeutic blockade of immune checkpoints has revolutionized cancer treatment. Durable responses, however, occur in less than half of those treated, and efforts to improve treatment efficacy are confounded by a lack of understanding of the characteristics of the cells that initiate antitumor immune response. Experimental Design: We performed multiparameter flow cytometry and quantitative multiplex immunofluorescence staining on tumor specimens from immunotherapy-naïve melanoma patients and longitudinal biopsy specimen obtained from patients undergoing anti-PD-1 therapy...
March 29, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29593708/mucosal-delivery-of-fusion-proteins-with-bacillus-subtilis-spores-enhances-protection-against-tuberculosis-by-bacillus-calmette-gu%C3%A3-rin
#17
Alastair Copland, Gil R Diogo, Peter Hart, Shane Harris, Andy C Tran, Mathew J Paul, Mahavir Singh, Simon M Cutting, Rajko Reljic
Tuberculosis (TB) is the most deadly infectious disease in existence, and the only available vaccine, Bacillus Calmette-Guérin (BCG), is almost a century old and poorly protective. The immunological complexity of TB, coupled with rising resistance to antimicrobial therapies, necessitates a pipeline of diverse novel vaccines. Here, we show that Bacillus subtilis spores can be coated with a fusion protein 1 ("FP1") consisting of Mycobacterium tuberculosis (Mtb) antigens Ag85B, ACR, and HBHA. The resultant vaccine, Spore-FP1, was tested in a murine low-dose Mtb aerosol challenge model...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29593283/breast-and-pancreatic-cancer-interrupt-irf8-dependent-dendritic-cell-development-to-overcome-immune-surveillance
#18
Melissa A Meyer, John M Baer, Brett L Knolhoff, Timothy M Nywening, Roheena Z Panni, Xinming Su, Katherine N Weilbaecher, William G Hawkins, Cynthia Ma, Ryan C Fields, David C Linehan, Grant A Challen, Roberta Faccio, Rebecca L Aft, David G DeNardo
Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, whereby the expansion of immunosuppressive myeloid cells can impair tumor immunity. As myeloid cells and conventional dendritic cells (cDCs) are derived from the same progenitors, we postulated that myelopoiesis might impact cDC development. The cDC subset, cDC1, which includes human CD141+ DCs and mouse CD103+ DCs, supports anti-tumor immunity by stimulating CD8+ T-cell responses. Here, to understand how cDC1 development changes during tumor progression, we investigated cDC bone marrow progenitors...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29581197/tnf%C3%AE-antagonism-reveals-a-gut-lung-axis-that-amplifies-regulatory-t-cells-in-a-pulmonary-fungal-infection
#19
Jamie L Tweedle, George S Deepe
Tumor necrosis factor (TNF) antagonists are popular therapies for inflammatory diseases. These agents enhance numbers and function of regulatory T cells (Tregs) which are important in controlling inflammatory diseases. However, elevated Tregs increase susceptibility to infections, including histoplasmosis. We determined the mechanism by which Tregs expand in TNF-neutralized mice infected with Histoplasma capsulatum Lung CD11c+ CD11b+ dendritic cells (DC), but not alveolar macrophages, from H. capsulatum -infected mice treated with anti-TNF induced a higher percentage of Tregs than control DC in vitro...
March 26, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29563179/skin-resident-t-cells-drive-dermal-dendritic-cell-migration-in-response-to-tissue-self-antigen
#20
Niwa Ali, Bahar Zirak, Hong-An Truong, Megan M Maurano, Iris K Gratz, Abul K Abbas, Michael D Rosenblum
Migratory dendritic cell (DC) subsets deliver tissue Ags to draining lymph nodes (DLNs) to either initiate or inhibit T cell-mediated immune responses. The signals mediating DC migration in response to tissue self-antigen are largely unknown. Using a mouse model of inducible skin-specific self-antigen expression, we demonstrate that CD103+ dermal DCs (DDCs) rapidly migrate from skin to skin DLN (SDLNs) within the first 48 h after Ag expression. This window of time was characterized by the preferential activation of tissue-resident Ag-specific effector T cells (Teffs), with no concurrent activation of Ag-specific Teffs in SDLNs...
May 1, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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