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tissue resident memory t cells

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https://www.readbyqxmd.com/read/29021139/paxillin-binding-to-the-cytoplasmic-domain-of-cd103-promotes-cell-adhesion-and-effector-functions-for-cd8-resident-memory-t-cells-in-tumors
#1
Ludiane Gauthier, Stephanie Corgnac, Marie Boutet, Gwendoline Gros, Pierre Validire, Georges Bismuth, Fathia Mami-Chouaib
CD8+/CD103+ tissue resident memory T cells (TRM cells) accumulate in several human solid tumors where they have been associated with a favorable prognosis. However, the role of CD103 - the α subunit of the integrin αEβ7 (also known as CD103) - in the retention and functions of these TRM is undefined. In this report, we investigated the role of CD103 cytoplasmic domain and the focal adhesion-associated protein paxillin (Pxn) in downstream signaling and functional activities triggered through αE/CD103 chain...
October 11, 2017: Cancer Research
https://www.readbyqxmd.com/read/28956763/a-novel-role-for-il-17-in-enhancing-type-1-helper-t-cell-immunity-in-the-female-genital-tract-following-mucosal-hsv-2-vaccination
#2
Puja Bagri, Varun C Anipindi, Philip V Nguyen, Danielle Vitali, Martin R Stämpfli, Charu Kaushic
It is well established that interferon-gamma (IFN-γ) production by CD4(+) T cells is critical for anti-viral immunity against herpes simplex virus type 2 (HSV-2) genital infection. However, the role of interleukin-17A (IL-17A) production by CD4(+) T cells in HSV-2 anti-viral immunity is yet to be elucidated. Here, we demonstrate that IL-17A plays an important role in enhancing anti-viral T helper type 1 (Th1) responses in the female genital tract (FGT), and is essential for effective protection conferred by HSV-2 vaccination...
September 27, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28948612/il-2-is-required-for-the-generation-of-viral-specific-cd4-th1-tissue-resident-memory-cells-and-b-cells-are-essential-for-maintenance-in-the-lung
#3
Brian D Hondowicz, Karen S Kim, Mikel J Ruterbusch, Gladys J Keitany, Marion Pepper
CD4(+) tissue resident cells are an important first line of defense against viral infections in the lungs and are critical for promoting the localization of lung resident CD8(+) T cells. However, relatively little is known about the signaling programs required for the development of viral-specific CD4(+) tissue resident cells in the lungs. Recently, it was shown that signaling through the high affinity IL-2 receptor is required for the differentiation of lung-resident Th2 memory (Trm) cells in a murine model of airway inflammation...
September 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28942919/organism-level-analysis-of-vaccination-reveals-networks-of-protection-across-tissues
#4
Motohiko Kadoki, Ashwini Patil, Cornelius C Thaiss, Donald J Brooks, Surya Pandey, Deeksha Deep, David Alvarez, Ulrich H von Andrian, Amy J Wagers, Kenta Nakai, Tarjei S Mikkelsen, Magali Soumillon, Nicolas Chevrier
A fundamental challenge in immunology is to decipher the principles governing immune responses at the whole-organism scale. Here, using a comparative infection model, we observe immune signal propagation within and between organs to obtain a dynamic map of immune processes at the organism level. We uncover two inter-organ mechanisms of protective immunity mediated by soluble and cellular factors. First, analyzing ligand-receptor connectivity across tissues reveals that type I IFNs trigger a whole-body antiviral state, protecting the host within hours after skin vaccination...
October 5, 2017: Cell
https://www.readbyqxmd.com/read/28930685/human-tissue-resident-memory-t-cells-are-defined-by-core-transcriptional-and-functional-signatures-in-lymphoid-and-mucosal-sites
#5
Brahma V Kumar, Wenji Ma, Michelle Miron, Tomer Granot, Rebecca S Guyer, Dustin J Carpenter, Takashi Senda, Xiaoyun Sun, Siu-Hong Ho, Harvey Lerner, Amy L Friedman, Yufeng Shen, Donna L Farber
Tissue-resident memory T cells (TRMs) in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69(+) subset of memory CD4(+) and CD8(+) T cells in lung and spleen that is distinct from that of CD69(-) TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8(+) TRMs...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28920584/liver-resident-nk-cells-and-their-potential-functions
#6
Hui Peng, Rui Sun
Natural killer (NK) cells represent a heterogeneous population of innate lymphocytes with phenotypically and functionally distinct subsets. In particular, recent studies have identified a unique subset of NK cells residing within the liver that are maintained as tissue-resident cells, confer antigen-specific memory responses and exhibit different phenotypical and developmental characteristics compared with conventional NK (cNK) cells. These findings have encouraged researchers to uncover tissue-resident NK cells at other sites, and detailed analyses have revealed that these tissue-resident NK cells share many similarities with liver-resident NK cells and tissue-resident memory T cells...
September 18, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28910403/polymicrobial-sepsis-impairs-bystander-recruitment-of-effector-cells-to-infected-skin-despite-optimal-sensing-and-alarming-function-of-skin-resident-memory-cd8-t-cells
#7
Derek B Danahy, Scott M Anthony, Isaac J Jensen, Stacey M Hartwig, Qiang Shan, Hai-Hui Xue, John T Harty, Thomas S Griffith, Vladimir P Badovinac
Sepsis is a systemic infection that enhances host vulnerability to secondary infections normally controlled by T cells. Using CLP sepsis model, we observed that sepsis induces apoptosis of circulating memory CD8 T-cells (TCIRCM) and diminishes their effector functions, leading to impaired CD8 T-cell mediated protection to systemic pathogen re-infection. In the context of localized re-infections, tissue resident memory CD8 T-cells (TRM) provide robust protection in a variety of infectious models. TRM rapidly 'sense' infection in non-lymphoid tissues and 'alarm' the host by enhancing immune cell recruitment to the site of the infection to accelerate pathogen clearance...
September 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28872670/tcr-pmhc-encounter-differentially-regulates-transcriptomes-of-tissue-resident-cd8-t%C3%A2-cells
#8
Akihiro Yoshizawa, Kevin Bi, Derin B Keskin, Guanglan Zhang, Bruce Reinhold, Ellis L Reinherz
To investigate the role of TCR-pMHC interaction in regulating lung CD8 tissue-resident T cell (TR ) differentiation, polyclonal responses were compared against NP366-374 /D(b) and PA224-233 /D(b) , two immunodominant epitopes that arise during influenza A infection in mice. Memory niches distinct from iBALTs develop within the lamina propria, supporting CD103(+) and CD103(-) CD8 TR generation and intraepithelial translocation. Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) identify dominant TCR, adherens junction, RIG-I-like and NOD-like pattern recognition receptor as well as TGF-β signaling pathways and memory signatures among PA224-233 /D(b) T cells consistent with T resident memory (TRM ) status...
September 5, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28860025/hepatitis-e-virus-induced-primary-cutaneous-cd30-t-cell-lymphoproliferative-disorder
#9
Vincent Mallet, Julie Bruneau, Julien Zuber, Cécile Alanio, Stéphanie Leclerc-Mercier, Anne-Marie Roque-Afonso, Anke R M Kraft, Lucile Couronné, Dominique Roulot, Heiner Wedemeyer, Matthew L Albert, Patrick Hillon, Liliane Laroche, Stanislas Pol, Olivier Hermine
BACKGROUND AND AIM: Several types of unexplained extra-hepatic manifestations, including haematological disorders, have been reported in the context of hepatitis E virus (HEV) infection. However, the underlying mechanism(s) of these manifestations are unknown. We provide evidence that HEV has an extra-hepatic endothelial tropism that can engage cutaneous T cells towards clonality. PATIENT AND METHODS: A patient with a CD30(+) cutaneous T cell lymphoproliferative disorder (T-LPD) and biopsy-proven chronic HEV infection received 3 rounds of oral ribavirin treatment administered either without or with interferon and eventually achieved a sustained virological response (SVR)...
August 28, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28855310/chemokine-receptor-dependent-control-of-skin-tissue-resident-memory-t-cell-formation
#10
Ali Zaid, Jyh Liang Hor, Susan N Christo, Joanna R Groom, William R Heath, Laura K Mackay, Scott N Mueller
Infection or inflammation of the skin recruits effector CD8(+) T cells that enter the epidermis and form populations of long-lived tissue-resident memory T (TRM) cells. These skin TRM cells migrate within the constrained epidermal environment by extending multiple dynamic dendritic projections and squeezing between keratinocytes to survey the tissue for pathogens. In this study, we examined the signals required for this distinctive mode of T cell migration by inhibiting key cytoskeletal components and performing intravital two-photon microscopy to visualize TRM cell behavior...
August 30, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28855242/reduced-generation-of-lung-tissue-resident-memory-t-cells-during-infancy
#11
Kyra D Zens, Jun Kui Chen, Rebecca S Guyer, Felix L Wu, Filip Cvetkovski, Michelle Miron, Donna L Farber
Infants suffer disproportionately from respiratory infections and generate reduced vaccine responses compared with adults, although the underlying mechanisms remain unclear. In adult mice, lung-localized, tissue-resident memory T cells (TRMs) mediate optimal protection to respiratory pathogens, and we hypothesized that reduced protection in infancy could be due to impaired establishment of lung TRM. Using an infant mouse model, we demonstrate generation of lung-homing, virus-specific T effectors after influenza infection or live-attenuated vaccination, similar to adults...
October 2, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28842633/expression-and-role-of-vla-1-in-resident-memory-cd8-t-cell-responses-to-respiratory-mucosal-viral-vectored-immunization-against-tuberculosis
#12
Siamak Haddadi, Niroshan Thanthrige-Don, Sam Afkhami, Amandeep Khera, Mangalakumari Jeyanathan, Zhou Xing
Lung resident memory T cells (TRM) characterized by selective expression of mucosal integrins VLA-1 (α1β1) and CD103 (αEβ7) are generated following primary respiratory viral infections. Despite recent progress, the generation of lung TRM and the role of mucosal integrins following viral vector respiratory mucosal immunization still remains poorly understood. Here by using a replication-defective viral vector tuberculosis vaccine, we show that lung Ag-specific CD8 T cells express both VLA-1 and CD103 following respiratory mucosal immunization...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28832609/distinct-aging-profiles-of-cd8-t-cells-in-blood-versus-gastrointestinal-mucosal-compartments
#13
Jeffrey Dock, Christina M Ramirez, Lance Hultin, Mary Ann Hausner, Patricia Hultin, Julie Elliott, Otto O Yang, Peter A Anton, Beth D Jamieson, Rita B Effros
A hallmark of human immunosenescence is the accumulation of late-differentiated memory CD8+ T cells with features of replicative senescence, such as inability to proliferate, absence of CD28 expression, shortened telomeres, loss of telomerase activity, enhanced activation, and increased secretion of inflammatory cytokines. Importantly, oligoclonal expansions of these cells are associated with increased morbidity and mortality risk in elderly humans. Currently, most information on the adaptive immune system is derived from studies using peripheral blood, which contains approximately only 2% of total body lymphocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28814601/il-15-complexes-induce-migration-of-resting-memory-cd8-t-cells-into-mucosal-tissues
#14
Ryan T Sowell, Josef W Goldufsky, Magdalena Rogozinska, Zurisaday Quiles, Yanxia Cao, Eliseo F Castillo, Alison Finnegan, Amanda L Marzo
IL-15 is an essential cytokine known to promote T cell survival and activate the effector function of memory phenotype CD8 T cells. Blocking IL-15 signals also significantly impacts tissue-specific effector and memory CD8 T cell formation. In this study, we demonstrate that IL-15 influences the generation of memory CD8 T cells by first promoting their accumulation into mucosal tissues and second by sustaining expression of Bcl-6 and T-bet. We show that the mechanism for this recruitment is largely dependent on mammalian target of rapamycin and its subsequent inactivation of FoxO1...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28783666/dynamics-of-influenza-induced-lung-resident-memory-t-cells-underlie-waning-heterosubtypic-immunity
#15
Bram Slütter, Natalija Van Braeckel-Budimir, Georges Abboud, Steven M Varga, Shahram Salek-Ardakani, John T Harty
Lung-resident memory CD8 T cells (TRM) induced by influenza A virus (IAV) that are pivotal for providing subtype-transcending protection against IAV infection (heterosubtypic immunity) are not maintained long term, causing gradual loss of protection. The short-lived nature of lung TRM contrasts sharply with long-term maintenance of TRM induced by localized infections in the skin and in other tissues. We show that the decline in lung TRM is determined by an imbalance between apoptosis and lung recruitment and conversion to TRM of circulating memory cells...
January 6, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783656/resident-memory-cd8-t-cells-in-the-upper-respiratory-tract-prevent-pulmonary-influenza-virus-infection
#16
Angela Pizzolla, Thi H O Nguyen, Jeffrey M Smith, Andrew G Brooks, Katherine Kedzieska, William R Heath, Patrick C Reading, Linda M Wakim
Nasal epithelial tissue of the upper respiratory tract is the first site of contact by inhaled pathogens such as influenza virus. We show that this region is key to limiting viral spread to the lower respiratory tract and associated disease pathology. Immunization of the upper respiratory tract leads to the formation of local tissue-resident memory CD8(+) T cells (Trm cells). Unlike Trm cells in the lung, these cells develop independently of local cognate antigen recognition and transforming growth factor-β signaling and persist with minimal decay, representing a long-term protective population...
June 2, 2017: Science Immunology
https://www.readbyqxmd.com/read/28782508/circulating-and-tissue-resident-cd4-t-cells-with-reactivity-to-intestinal-microbiota-are-abundant-in-healthy-individuals-and-function-is-altered-during-inflammation
#17
Ahmed N Hegazy, Nathaniel R West, Michael J T Stubbington, Emily Wendt, Kim I M Suijker, Angeliki Datsi, Sebastien This, Camille Danne, Suzanne Campion, Sylvia H Duncan, Benjamin M J Owens, Holm H Uhlig, Andrew McMichael
BACKGROUND & AIMS: Interactions between commensal microbes and the immune system are tightly regulated and maintain intestinal homeostasis, but little is known about these interactions in humans. We investigated responses of human CD4(+) T cells to the intestinal microbiota. We measured the abundance of T cells in circulation and intestinal tissues that respond to intestinal microbes and determined their clonal diversity. We also assessed their functional phenotypes and effects on intestinal resident cell populations, and studied alterations in microbe-reactive T cells in patients with chronic intestinal inflammation...
August 4, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28762530/high-proportion-of-pd-1-expressing-cd4-t-cells-in-adipose-tissue-constitutes-an-immunomodulatory-microenvironment-that-may-support-hiv-persistence
#18
Abderaouf Damouche, Guillaume Pourcher, Valérie Pourcher, Stéphane Benoist, Elodie Busson, Jean Jacques Lataillade, Mélanie Le Van, Thierry Lazure, Julien Adam, Benoit Favier, Bruno Vaslin, Michaela Müller-Trutwin, Olivier Lambotte, Christine Bourgeois
We and others have demonstrated that adipose tissue is a reservoir for HIV. Evaluation of the mechanisms responsible for viral persistence may lead to ways of reducing these reservoirs. Here, we evaluated the immune characteristics of adipose tissue in HIV-infected patients receiving antiretroviral therapy (ART) and in non-HIV-infected patients. We notably sought to determine whether adipose tissue's intrinsic properties and/or HIV induced alteration of the tissue environment may favour viral persistence. ART-controlled HIV infection was associated with a difference in the CD4/CD8 T-cell ratio and an elevated proportion of Treg cells in subcutaneous adipose tissue...
August 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28754914/memory-type-st2-cd4-t-cells-participate-in-the-steroid-resistant-pathology-of-eosinophilic-pneumonia
#19
Naoko Mato, Kiyoshi Hirahara, Tomomi Ichikawa, Jin Kumagai, Masayuki Nakayama, Hideaki Yamasawa, Masashi Bando, Koichi Hagiwara, Yukihiko Sugiyama, Toshinori Nakayama
The lung develops an unique epithelial barrier system to protect host from continuous invasion of various harmful particles. Interleukin (IL-)33 released from epithelial cells in the lung drives the type 2 immune response by activating ST2- expressed immune cells in various allergic diseases. However, the involvement of memory-type ST2(+)CD4(+) T cells in such lung inflammation remains unclear. Here we demonstrated that intratracheal administration of IL-33 resulted in the substantial increase of numbers of tissue-resident memory-type ST2(+)CD4(+) T cells in the lung...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28738020/resident-memory-t-cells-in-the-skin-mediate-durable-immunity-to-melanoma
#20
Brian T Malik, Katelyn T Byrne, Jennifer L Vella, Peisheng Zhang, Tamer B Shabaneh, Shannon M Steinberg, Aleksey K Molodtsov, Jacob S Bowers, Christina V Angeles, Chrystal M Paulos, Yina H Huang, Mary Jo Turk
Tissue-resident memory T (TRM) cells have been widely characterized in infectious disease settings; however, their role in mediating immunity to cancer remains unknown. We report that skin-resident memory T cell responses to melanoma are generated naturally as a result of autoimmune vitiligo. Melanoma antigen-specific TRM cells resided predominantly in melanocyte-depleted hair follicles and were maintained without recirculation or replenishment from the lymphoid compartment. These cells expressed CD103, CD69, and CLA (cutaneous lymphocyte antigen), but lacked PD-1 (programmed cell death protein-1) or LAG-3 (lymphocyte activation gene-3), and were capable of making IFN-γ (interferon-γ)...
April 14, 2017: Science Immunology
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