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https://www.readbyqxmd.com/read/29311695/local-proliferation-maintains-a-stable-pool-of-tissue-resident-memory-t-cells-after-antiviral-recall-responses
#1
Simone L Park, Ali Zaid, Jyh Liang Hor, Susan N Christo, Julia E Prier, Brooke Davies, Yannick O Alexandre, Julia L Gregory, Tiffany A Russell, Thomas Gebhardt, Francis R Carbone, David C Tscharke, William R Heath, Scott N Mueller, Laura K Mackay
Although tissue-resident memory T cells (TRM cells) are critical in fighting infection, their fate after local pathogen re-encounter is unknown. Here we found that skin TRM cells engaged virus-infected cells, proliferated in situ in response to local antigen encounter and did not migrate out of the epidermis, where they exclusively reside. As a consequence, secondary TRM cells formed from pre-existing TRM cells, as well as from precursors recruited from the circulation. Newly recruited antigen-specific or bystander TRM cells were generated in the skin without displacement of the pre-existing TRM cell pool...
January 8, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29311694/intravital-mucosal-imaging-of-cd8-resident-memory-t-cells-shows-tissue-autonomous-recall-responses-that-amplify-secondary-memory
#2
Lalit K Beura, Jason S Mitchell, Emily A Thompson, Jason M Schenkel, Javed Mohammed, Sathi Wijeyesinghe, Raissa Fonseca, Brandon J Burbach, Heather D Hickman, Vaiva Vezys, Brian T Fife, David Masopust
CD8+ T cell immunosurveillance dynamics influence the outcome of intracellular infections and cancer. Here we used two-photon intravital microscopy to visualize the responses of CD8+ resident memory T cells (TRM cells) within the reproductive tracts of live female mice. We found that mucosal TRM cells were highly motile, but paused and underwent in situ division after local antigen challenge. TRM cell reactivation triggered the recruitment of recirculating memory T cells that underwent antigen-independent TRM cell differentiation in situ...
January 8, 2018: Nature Immunology
https://www.readbyqxmd.com/read/29296781/clinical-profile-biological-markers-and-comorbidity-index-as-predictors-of-transplant-related-mortality-after-allo-hsct
#3
Aliénor Xhaard, Renato Cunha, Marc Busson, Marie Robin, Nathalie Dhedin, Tereza Coman, Aurélie Cabannes-Hamy, Flore Sicre de Fontbrune, David Michonneau, Gérard Socié, Rodrigo T Calado, Régis Peffault de Latour
Various pretransplant patient and disease characteristics are associated with treatment-related mortality (TRM) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, TRM cannot yet be satisfactorily predicted. We prospectively investigated the aggregate impact of pretransplant clinical variables (period, donor/recipient age, gender, cytomegalovirus status, disease risk, stem cell source, and HLA matching), comorbidity index scores (Hematopoietic Cell Transplantation Comorbidity Index), and biological markers (telomere length, ferritin, and C-reactive protein) on TRM in single-center patients receiving a first allo-HSCT...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29279357/successful-outcome-following-allogeneic-hematopoietic-stem-cell-transplantation-in-adults-with-primary-immunodeficiency
#4
Thomas A Fox, Ronjon Chakraverty, Siobhan Burns, Benjamin Carpenter, Kirsty Thomson, David Lowe, Adele Fielding, Karl Peggs, Panagiotis Kottaridis, Benjamin Uttenthal, Venetia Bigley, Matthew Buckland, Victoria Grandage, Shari Denovan, Sarah Grace, Julia Dahlstrom, Sarita Workman, Andrew Symes, Stephen Mackinnon, Rachael Hough, Emma Morris
INTRODUCTION: The primary immunodeficiencies (PID), rare inherited diseases characterised by severe dysfunction of immunity have been successfully treated by allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in childhood. Controversy exists regarding optimal timing and use of Allo-HSCT in adults, due to lack of experience and previous poor outcomes. MATERIALS AND METHODS: 29 consecutive adult patients, with a mean age at transplant of 24 years (range 17-50) underwent Allo-HSCT...
December 26, 2017: Blood
https://www.readbyqxmd.com/read/29275139/pre-transplant-consolidation-is-not-beneficial-for-adults-with-all-undergoing-myeloablative-allogeneic-transplantation
#5
Nelli Bejanyan, Mei-Jie Zhang, Hai-Lin Wang, Aleksandr Lazaryan, Marcos de Lima, David I Marks, Brenda M Sandmaier, Veronika Bachanova, Jacob Rowe, Martin Tallman, Partow Kebriaei, Mohamed Kharfan-Dabaja, Robert Peter Gale, Hillard M Lazarus, Celalettin Ustun, Edward Copelan, Betty Ky Hamilton, Gary Schiller, William Hogan, Shahrukh Hashmi, Matthew Seftel, Christopher Kanakry, Richard F Olsson, Rodrigo Martino, Wael Saber, H Jean Khoury, Daniel J Weisdorf
Allogeneic hematopoietic cell transplantation (alloHCT) is curative for patients with acute lymphoblastic leukemia (ALL) who achieve complete remission (CR1) with chemotherapy. However, the benefit of consolidation chemotherapy remains uncertain in patients undergoing alloHCT. We compared clinical outcomes of 524 adult patients with ALL in CR1 who received ≥2 (n=109), 1 (n=93), or 0 cycles (n=322) of consolidation prior to myeloablative alloHCT from 2008-2012. As expected, time to alloHCT was longer with increasing cycles of consolidation...
December 21, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29262342/the-skinny-on-fat-trm-cells
#6
Stanley Cheuk, Liv Eidsmo
White adipose tissue (WAT) is exposed to pathogens that breach epithelial barriers, but the role of adipose T cells in immunity isn't clear. In this issue of Immunity, Han et al. (2017) find that WAT harbors a reservoir of memory T cells that provide antimicrobial immunity at the expense of lipid synthesis and metabolism.
December 19, 2017: Immunity
https://www.readbyqxmd.com/read/29239087/danaparoid-reduces-transplant-related-mortality-in-stem-cell-transplantation-for-children
#7
Koji Kato, Hirotoshi Sakaguchi, Hideki Muramatsu, Yuko Sekiya, Nozomu Kawashima, Atsushi Narita, Sayoko Doisaki, Nobuhiro Watanabe, Nao Yoshida, Kimikazu Matsumoto
In SCT, death from transplant-related complications is the major obstacle hindering improvement of transplant outcomes, and proper supportive care is essential to reduce TRM. The transplant outcomes of 210 pediatric patients with malignant and non-malignant disorders who consecutively underwent SCT in our institution from 2000 to 2013 were analyzed. The transplant years were divided into three periods: A (2000-2004), B (2005-2008), and C (2009-2013), and an improvement in 5-year OS and a decrease in 5-year TRM were observed over these time periods; that is, OS was 61...
December 13, 2017: Pediatric Transplantation
https://www.readbyqxmd.com/read/29225163/impact-of-dose-adjusted-melphalan-in-obese-patients-undergoing-autologous-stem-cell-transplantation
#8
Kendall Shultes, Christopher Arp, Keith Stockerl-Goldstein, Kathryn Trinkaus, Sean DeFrates
BACKGROUND: Limited guidance exists for dosing melphalan (MEL) for autologous stem cell transplantation (ASCT) in the obese patient population as the current literature reports conflicting clinical outcomes between obese and non-obese patients. In 2014, the American Society for Blood and Marrow Transplantation published conditioning chemotherapy dosing guidelines for obese patients and recommended MEL be dosed utilizing actual body weight (ABW) in the body surface area calculation. Practice at Barnes-Jewish Hospital has consistently been to dose MEL using an adjusted body weight (AdBW) with a 20% correction when patients weigh greater than or equal to 120% their ideal body weight (IBW)...
December 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29211713/runx3-programs-cd8-t-cell-residency-in-non-lymphoid-tissues-and-tumours
#9
J Justin Milner, Clara Toma, Bingfei Yu, Kai Zhang, Kyla Omilusik, Anthony T Phan, Dapeng Wang, Adam J Getzler, Toan Nguyen, Shane Crotty, Wei Wang, Matthew E Pipkin, Ananda W Goldrath
Tissue-resident memory CD8+ T (TRM) cells are found at common sites of pathogen exposure, where they elicit rapid and robust protective immune responses. However, the molecular signals that control TRM cell differentiation and homeostasis are not fully understood. Here we show that mouse TRM precursor cells represent a unique CD8+ T cell subset that is distinct from the precursors of circulating memory cell populations at the levels of gene expression and chromatin accessibility. Using computational and pooled in vivo RNA interference screens, we identify the transcription factor Runx3 as a key regulator of TRM cell differentiation and homeostasis...
December 6, 2017: Nature
https://www.readbyqxmd.com/read/29196729/peripheral-t-follicular-helper-cells-make-a-difference-in-hiv-reservoir-size-between-elite-controllers-and-patients-on-successful-cart
#10
Marcial García, Miguel Górgolas, Alfonso Cabello, Vicente Estrada, José Manuel Ligos, Manuel Fernández-Guerrero, Carlos Barros, Juan Carlos López-Bernaldo, Francisco Javier De La Hera, María Montoya, José Miguel Benito, Norma Rallón
HIV latency is the main barrier to HIV eradication. Peripheral T follicular helper (pTfh) cells have a prominent role in HIV persistence. Herein, we analyzed the HIV reservoir size within memory CD4+ T-cell subsets in patients with HIV replication control. Twenty HIV-infected patients with suppressed HIV replication were included, with 10 elite controllers (EC) and 10 treated (TX) individuals. The HIV reservoir size was analyzed in resting memory CD4+ T-cells (Trm), pTfh, and non-pTfh cells using an ultrasensitive digital-droplet-PCR assay...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29186108/il-15-supports-the-generation-of-protective-lung-resident-memory-cd4-t-cells
#11
T M Strutt, K Dhume, C M Finn, J H Hwang, C Castonguay, S L Swain, K K McKinstry
Tissue-resident memory T cells (TRM) provide optimal defense at the sites of infection, but signals regulating their development are unclear, especially for CD4 T cells. Here we identify two distinct pathways that lead to the generation of CD4 TRM in the lungs following influenza infection. The TRM are transcriptionally distinct from conventional memory CD4 T cells and share a gene signature with CD8 TRM. The CD4 TRM are superior cytokine producers compared with conventional memory cells, can protect otherwise naive mice against a lethal influenza challenge, and display functional specialization by inducing enhanced inflammatory responses from dendritic cells compared with conventional memory cells...
November 29, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/29175730/formation-and-function-of-tissue-resident-memory-t-cells-during-viral-infection
#12
REVIEW
Haina Shin
Memory T cells are an important component of the adaptive immune response. Tissue-resident memory T cells (TRM) are a recently described subset of memory T cells that reside in peripheral tissues and are maintained independently of circulating subsets of memory T cells. Importantly, TRM are frequently found in barrier tissues that commonly serve as entry portals for pathogens such as viruses. Mounting evidence shows that TRM are superior to their circulating counterparts in conferring protective immunity against a wide range of viruses...
November 23, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/29171836/crig-a-tissue-resident-macrophage-specific-immune-checkpoint-molecule-promotes-immunological-tolerance-in-nod-mice-via-a-dual-role-in-effector-and-regulatory-t-cells
#13
Xiaomei Yuan, Bi-Huei Yang, Yi Dong, Asami Yamamura, Wenxian Fu
How tissue-resident macrophages (TRM) impact adaptive immune responses remains poorly understood. We report novel mechanisms by which TRMs regulate T cell activities at tissue sites. These mechanisms are mediated by the complement receptor of immunoglobulin family (CRIg). Using animal models for autoimmune type 1 diabetes (T1D), we found that CRIg+ TRMs formed a protective barrier surrounding pancreatic islets. Genetic ablation of CRIg exacerbated islet inflammation and local T cell activation. CRIg exhibited a dual function of attenuating early T cell activation and promoting the differentiation of Foxp3+ regulatory (Treg) cells...
November 24, 2017: ELife
https://www.readbyqxmd.com/read/29170671/b7-h1-influences-the-accumulation-of-virus-specific-tissue-resident-memory-t-cells-in-the-central-nervous-system
#14
Kevin D Pavelko, Michael P Bell, Susan M Harrington, Haidong Dong
Therapies that target the PD-1/B7-H1 axis have revolutionized cancer treatment, yet precise knowledge of how this pathway provides benefit continues to evolve. Here, we report a novel role for the immune checkpoint ligand B7-H1 in the accumulation of tissue-resident memory CD8(+) T-cells (TRM). After intracranial infection, Theiler's murine encephalomyelitis virus (TMEV) generates TRM that are maintained in the central nervous system (CNS) tissues of B7-H1(WT) animals. Although no differences in acute T-cell responses between B7-H1(WT) and B7-H1(KO) are observed, at long-term periods post-infection the maintenance of CD8(+) TRM is diminished in B7-H1(KO) animals...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29158429/b-cell-presentation-of-chlamydia-antigen-selects-out-protective-cd4%C3%AE-13-t-cells-implications-for-genital-tract-tissue-resident-memory-lymphocyte-clusters
#15
Raymond M Johnson, Hong Yu, Norma Olivares Strank, Karuna Karunakaran, Ying Zhu, Robert C Brunham
Surveillance and defense of the enormous mucosal interface with the nonsterile world is critical to protecting the host from a wide range of pathogens. Chlamydia trachomatis (Ct) is an intracellular bacterial pathogen that replicates almost exclusively in the epithelium of the reproductive tract. The fallopian tubes and vagina are poorly suited to surveillance and defense with limited immune infrastructure positioned near the epithelium. However, a dynamic process during clearing primary infections leaves behind new lymphoid clusters immediately beneath the epithelium...
November 20, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29156642/is-the-benefit-risk-ratio-for-patients-with-transfusion-dependent-thalassemia-treated-by-unrelated-cord-blood-transplantation-favorable
#16
REVIEW
Tang-Her Jaing
Transfusion-dependent thalassemia (TDT) is an inherited disorder characterized by absent or defective production of α- or β-hemoglobin chains. If untreated, the disease invariably culminates in death in early infancy due to cardiac failure or overwhelming infection. Although there is clear evidence of good health-related quality of life and return to normal life style, the choice to undergo hematopoietic stem cell transplantation (HSCT) remains a challenge because of the potential risk of transplant-related mortality (TRM) in TDT...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156204/autologous-hematopoietic-cell-transplantation-for-adult-acute-myeloid-leukemia-an-obsolete-or-resurfacing-concept
#17
REVIEW
Hillard M Lazarus, Najla El Jurdi
Improving long-term outcomes of adult acute myeloid leukemia (AML) patients remains a challenge. Major scientific and clinical advances have led to a better understanding of the disease biology, and the majority of patients achieve a complete remission (CR) after induction therapy. Relapse risk, however, remains considerable and is the leading cause of death in this patient population. Significant efforts to improve outcomes emphasize use of post-remission therapies such as hematopoietic cell transplantation (HCT), an increasingly utilized modality...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29147623/tissue-resident-memory-t-cells-play-a-key-role-in-the-efficacy-of-cancer-vaccines
#18
C Granier, C Blanc, S Karaki, T Tran, H Roussel, E Tartour
Resident memory CD8(+)T cells (TRM) usually defined by the CD103 marker represent a new subset of long-lived memory T cells that remain in the tissues. We directly demonstrate their specific role in cancer vaccine-induced tumor regression. In human, they also seem to play a major role in tumor immunosurveillance.
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29144232/saccharopolyspora-aidingensis-sp-nov-an-actinomycete-isolated-from-a-salt-lake
#19
Zhan-Feng Xia, Xiao-Xia Luo, Chuan-Xing Wan, Li-Li Zhang
A novel halophilic actinomycete strain, designated TRM 46074(T), was isolated from Aiding salt lake in Turpan Basin, north-west China. Strain TRM 46074(T) was aerobic, Gram-stain-positive and grew optimally with 12 % (w/v) NaCl. The strain was observed to produce sparse aerial mycelium with long chains of spores that were non-motile and oval or spherical in shape with a rough or smooth surface; substrate mycelium was branched and well developed. The cell wall was determined to contain meso-diaminopimelic acid; the diagnostic whole-cell sugars were galactose, arabinose and ribose...
March 2017: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/29139478/trigger-happy-resident-memory-cd4-t-cells-inhabit-the-human-lungs
#20
A E Oja, B Piet, C Helbig, R Stark, D van der Zwan, H Blaauwgeers, E B M Remmerswaal, D Amsen, R E Jonkers, P D Moerland, M A Nolte, R A W van Lier, P Hombrink
Resident memory T cells (TRM) reside in the lung epithelium and mediate protective immunity against respiratory pathogens. Although lung CD8+ TRM have been extensively characterized, the properties of CD4+ TRM remain unclear. Here we determined the transcriptional signature of CD4+ TRM, identified by the expression of CD103, retrieved from human lung resection material. Various tissue homing molecules were specifically upregulated on CD4+ TRM, whereas expression of tissue egress and lymph node homing molecules were low...
November 15, 2017: Mucosal Immunology
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