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tissue resident memory t cells

Pleun Hombrink, Christina Helbig, Ronald A Backer, Berber Piet, Anna E Oja, Regina Stark, Giso Brasser, Aldo Jongejan, René E Jonkers, Benjamin Nota, Onur Basak, Hans C Clevers, Perry D Moerland, Derk Amsen, René A W van Lier
Tissue-resident memory T cells (TRM cells) in the airways mediate protection against respiratory infection. We characterized TRM cells expressing integrin αE (CD103) that reside within the epithelial barrier of human lungs. These cells had specialized profiles of chemokine receptors and adhesion molecules, consistent with their unique localization. Lung TRM cells were poised for rapid responsiveness by constitutive expression of deployment-ready mRNA encoding effector molecules, but they also expressed many inhibitory regulators, suggestive of programmed restraint...
October 24, 2016: Nature Immunology
Emma C Reilly, Kris Lambert-Emo, David J Topham
After disease resolution, a small subset of influenza specific CD8+ T cells can remain in the airways of the lung as a tissue resident memory population (TRM). These cells are critical for protection from subsequent infections with heterosubtypic influenza viruses. Although it is well established that expression of the collagen IV binding integrin alpha 1 is necessary for the retention and maintenance of TRM cells, other requirements allowing them to localize to the airways and persist are less well understood...
2016: PloS One
Michiel C van Aalderen, Ester B M Remmerswaal, Kirstin M Heutinck, Anja Ten Brinke, Mariet C W Feltkamp, Neelke C van der Weerd, Karlijn A M I van der Pant, Frederike J Bemelman, René A W van Lier, Ineke J M Ten Berge
Polyomavirus BK (BKPyV) frequently reactivates in immunosuppressed renal transplant recipients (RTRs) and may lead to graft loss due to BKPyV-induced interstitial nephritis (BKVN). Little is known on the differentiation of CD8+ T cells targeting BKPyV in RTRs. Here we investigated whether BKPyV-specific CD8+ T cell differentiation differs in RTRs with varying degrees of BKPyV reactivation and/or BKVN. Using combinatorial encoding with tetramers carrying BKPyV major capsid protein (VP1) and large T antigen protein (LTAG) epitopes, we investigated CD8+ T cell responses to BKPyV in longitudinally obtained PBMC samples from 46 HLA-A02-positive RTRs and 20 healthy adults...
October 2016: PLoS Pathogens
Corinne J Smith, Michael Quinn, Christopher M Snyder
Human cytomegalovirus (HCMV) is a ubiquitous virus that causes chronic infection and, thus, is one of the most common infectious complications of immune suppression. Adoptive transfer of HCMV-specific T cells has emerged as an effective method to reduce the risk for HCMV infection and/or reactivation by restoring immunity in transplant recipients. However, the CMV-specific CD8(+) T cell response is comprised of a heterogenous mixture of subsets with distinct functions and localization, and it is not clear if current adoptive immunotherapy protocols can reconstitute the full spectrum of CD8(+) T cell immunity...
2016: Frontiers in Immunology
Salvador Iborra, María Martínez-López, Sofía C Khouili, Michel Enamorado, Francisco J Cueto, Ruth Conde-Garrosa, Carlos Del Fresno, David Sancho
Despite the crucial role of tissue-resident memory T (Trm) cells in protective immunity, their priming remains poorly understood. Here, we have shown differential priming requirements for Trm versus circulating memory CD8(+) T cells. In vaccinia cutaneous-infected mice, DNGR-1-mediated crosspresentation was required for optimal Trm cell priming but not for their skin differentiation or for circulating memory T cell generation. DNGR-1(+) dendritic cells (DCs) promoted T-bet transcription-factor induction and retention of CD8(+) T cells in the lymph nodes (LNs)...
September 24, 2016: Immunity
Daniel Fernandez-Ruiz, Wei Yi Ng, Lauren E Holz, Joel Z Ma, Ali Zaid, Yik Chun Wong, Lei Shong Lau, Vanessa Mollard, Anton Cozijnsen, Nicholas Collins, Jessica Li, Gayle M Davey, Yu Kato, Sapna Devi, Roghieh Skandari, Michael Pauley, Jonathan H Manton, Dale I Godfrey, Asolina Braun, Szun Szun Tay, Peck Szee Tan, David G Bowen, Friedrich Koch-Nolte, Björn Rissiek, Francis R Carbone, Brendan S Crabb, Mireille Lahoud, Ian A Cockburn, Scott N Mueller, Patrick Bertolino, Geoffrey I McFadden, Irina Caminschi, William R Heath
In recent years, various intervention strategies have reduced malaria morbidity and mortality, but further improvements probably depend upon development of a broadly protective vaccine. To better understand immune requirement for protection, we examined liver-stage immunity after vaccination with irradiated sporozoites, an effective though logistically difficult vaccine. We identified a population of memory CD8(+) T cells that expressed the gene signature of tissue-resident memory T (Trm) cells and remained permanently within the liver, where they patrolled the sinusoids...
September 17, 2016: Immunity
Luhua H Zhang, June Ho Shin, Mikel D Haggadone, John B Sunwoo
A tissue-resident population of natural killer cells (NK cells) in the liver has recently been described to have the unique capacity to confer immunological memory in the form of hapten-specific contact hypersensitivity independent of T and B cells. Factors regulating the development and maintenance of these liver-resident NK cells are poorly understood. The aryl hydrocarbon receptor (AhR) is a transcription factor modulated by exogenous and endogenous ligands that is important in the homeostasis of immune cells at barrier sites, such as the skin and gut...
September 26, 2016: Journal of Experimental Medicine
Robert Zeiser, Gerard Socié, Bruce R Blazar
Acute graft-versus-host disease (aGVHD) is a major life-threatening complication of allogeneic haematopoietic cell transplantation (allo-HCT). Here we discuss the aGVHD pathophysiology initiated by multiple signals that cause alloreactive T-cell activation. The outcome of such donor T-cell activation is influenced by T-cell receptor-signal strength, anatomical location, co-stimulatory/co-inhibitory signals and differentiation stage (naive, effector/memory) of T-cells. Additionally, cross-priming of T cells to antigens expressed by pathogens can contribute to aGVHD-mediated tissue injury...
October 2016: British Journal of Haematology
Chandra Sekhar Boddupalli, Shiny Nair, Simon M Gray, Heba N Nowyhed, Rakesh Verma, Joanna A Gibson, Clara Abraham, Deepak Narayan, Juan Vasquez, Catherine C Hedrick, Richard A Flavell, Kavita M Dhodapkar, Susan M Kaech, Madhav V Dhodapkar
Immune surveillance in tissues is mediated by a long-lived subset of tissue-resident memory T cells (Trm cells). A putative subset of tissue-resident long-lived stem cells is characterized by the ability to efflux Hoechst dyes and is referred to as side population (SP) cells. Here, we have characterized a subset of SP T cells (Tsp cells) that exhibit a quiescent (G0) phenotype in humans and mice. Human Trm cells in the gut and BM were enriched in Tsp cells that were predominantly in the G0 stage of the cell cycle...
October 3, 2016: Journal of Clinical Investigation
A Rodrigues, M Claro, G Alexandre-Pires, D Santos-Mateus, C Martins, A Valério-Bolas, M Rafael-Fernandes, M A Pereira, I Pereira da Fonseca, A M Tomás, G Santos-Gomes
In the recent years, the liver has been recognized as an important immune organ with major regulatory functions and immune memory, adding to the well-described vital metabolic functions. There are evidences from experimental infections performed with visceral Leishmania species that immune responses to parasite infection can be organ-specific. The liver is the compartment of acute resolving infection, with minimal tissue damage and resistance to reinfection, whereas the spleen is the compartment of parasite persistence...
September 1, 2016: Immunobiology
Marco Diani, Gianfranco Altomare, Eva Reali
Psoriasis is a chronic inflammatory skin disease, which is associated with systemic inflammation and comorbidities, such as psoriatic arthritis and cardiovascular diseases. The autoimmune nature of psoriasis has been established only recently, conferring a central role to epidermal CD8 T cells recognizing self-epitopes in the initial phase of the disease. Different subsets of helper cells have also been reported as key players in the psoriasis pathogenesis. Here, we reviewed the knowledge on the role of each subset in the psoriatic cascade and in the different clinical manifestations of the disease...
2016: Journal of Immunology Research
Juan M Ilarregui, Astrid J van Beelen, Cynthia M Fehres, Sven C M Bruijns, Juan J García-Vallejo, Yvette van Kooyk
Interleukin (IL)-1β has proven to be crucial in the differentiation of human and mouse Th17 cells. Although it has become evident that IL-1β has potent IL-17-inducing effects on CD4(+) T cells directly, it has not yet been explored whether IL-1β can also prime dendritic cells (DCs) for a Th17 instruction program. Here, we show that human immature DCs exposed to IL-1β promote IL-17 production in human memory CD4(+) T cells. IL-1β-primed DCs express high levels of CD14 that mediate IL-17 production through direct interaction with T cells...
August 23, 2016: Immunology and Cell Biology
Heng Giap Woon, Asolina Braun, Jane Li, Corey Smith, Jarem Edwards, Frederic Sierro, Carl G Feng, Rajiv Khanna, Michael Elliot, Andrew Bell, Andrew D Hislop, Stuart G Tangye, Alan B Rickinson, Thomas Gebhardt, Warwick J Britton, Umaimainthan Palendira
Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation...
August 2016: PLoS Pathogens
Jessica K Fiege, Lalit K Beura, Brandon J Burbach, Yoji Shimizu
During acute infections, naive Ag-specific CD8 T cells are activated and differentiate into effector T cells, most of which undergo contraction after pathogen clearance. A small population of CD8 T cells persists as memory to protect against future infections. We investigated the role of adhesion- and degranulation-promoting adapter protein (ADAP) in promoting CD8 T cell responses to a systemic infection. Naive Ag-specific CD8 T cells lacking ADAP exhibited a modest expansion defect early after Listeria monocytogenes or vesicular stomatitis virus infection but comparable cytolytic function at the peak of response...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Jiangping Li, Sifei Yu, Yannan Zhang, Juan Shen, Suihua Lao, Baiqing Li, Binyan Yang, Changyou Wu
Control of infection with Mycobacterium tuberculosis (M.tb) requires effective antigen-specific immune response, including CD4(+) and CD8(+) T-cell responses; however, the local immune response of mucosal-associated invariant T (MAIT) cells at the site of infection is unclear. MAIT cells are a prevalent and unique, innate T-cell population that expresses the semi-invariant T-cell receptor TCRVα7.2. Our direct ex vivo analysis demonstrates that the frequency of MAIT cells in pleural fluid was much higher than that in peripheral blood from healthy donors, but much lower than that in peripheral blood from patients with tuberculosis...
August 9, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Se Jin Im, Masao Hashimoto, Michael Y Gerner, Junghwa Lee, Haydn T Kissick, Matheus C Burger, Qiang Shan, J Scott Hale, Judong Lee, Tahseen H Nasti, Arlene H Sharpe, Gordon J Freeman, Ronald N Germain, Helder I Nakaya, Hai-Hui Xue, Rafi Ahmed
Chronic viral infections are characterized by a state of CD8(+) T-cell dysfunction that is associated with expression of the programmed cell death 1 (PD-1) inhibitory receptor. A better understanding of the mechanisms that regulate CD8(+) T-cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8(+) T cells. Here we identify a population of virus-specific CD8(+) T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus (LCMV)...
August 2, 2016: Nature
Yusuke Tomita, Miwa Satomi, William Bracamonte Baran, Ewa Jankowska Gan, Andrea Szymczak Workman, Creg J Workman, Dario Angelo Alberto Vignali, William J Burlingham
BACKGROUND: The influence of donor-side regulation toward recipient antigens on graft outcome is poorly understood. METHODS: Because this influence might be due in part to the accumulation of tissue-resident memory T cells in the donor organ, we used a standard murine tolerization model (donor-specific transfusion plus CD40L blockade) to determine the kinetics of development and peripheralization of allospecific regulatory T cell in lymphoid tissues and liver, a secondary lymphoid organ used in transplantation...
May 2016: Transplantation Direct
Pavlo Gilchuk, Timothy M Hill, Clifford Guy, Sean R McMaster, Kelli L Boyd, Whitney A Rabacal, Pengcheng Lu, Yu Shyr, Jacob E Kohlmeier, Eric Sebzda, Douglas R Green, Sebastian Joyce
The nature and anatomic location of the protective memory CD8(+) T cell subset induced by intranasal vaccination remain poorly understood. We developed a vaccination model to assess the anatomic location of protective memory CD8(+) T cells and their role in lower airway infections. Memory CD8(+) T cells elicited by local intranasal, but not systemic, vaccination with an engineered non-replicative CD8(+) T cell-targeted antigen confer enhanced protection to a lethal respiratory viral challenge. This protection depends on a distinct CXCR3(LO) resident memory CD8(+) T (Trm) cell population that preferentially localizes to the pulmonary interstitium...
August 16, 2016: Cell Reports
Kyra D Zens, Jun Kui Chen, Donna L Farber
Tissue-resident memory T cells (TRM) are a recently defined, noncirculating subset with the potential for rapid in situ protective responses, although their generation and role in vaccine-mediated immune responses is unclear. Here, we assessed TRM generation and lung-localized protection following administration of currently licensed influenza vaccines, including injectable inactivated influenza virus (IIV, Fluzone) and i.n. administered live-attenuated influenza virus (LAIV, FluMist) vaccines. We found that, while IIV preferentially induced strain-specific neutralizing antibodies, LAIV generated lung-localized, virus-specific T cell responses...
July 7, 2016: JCI Insight
P A Romagnoli, H H Fu, Z Qiu, C Khairallah, Q M Pham, L Puddington, K M Khanna, L Lefrançois, B S Sheridan
Mucosal antigen-specific CD4 T-cell responses to intestinal pathogens remain incompletely understood. Here we examined the CD4 T-cell response after oral infection with an internalin A 'murinized' Listeria monocytogenes (Lm). Oral Lm infection induced a robust endogenous listeriolysin O (LLO)-specific CD4 T-cell response with distinct phenotypic and functional characteristics in the intestine. Circulating LLO-specific CD4 T cells transiently expressed the 'gut-homing' integrin α4β7 and accumulated in the intestinal lamina propria and epithelium where they were maintained independent of interleukin (IL)-15...
July 27, 2016: Mucosal Immunology
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