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https://www.readbyqxmd.com/read/28219080/survival-of-tissue-resident-memory-t-cells-requires-exogenous-lipid-uptake-and-metabolism
#1
Youdong Pan, Tian Tian, Chang Ook Park, Serena Y Lofftus, Shenglin Mei, Xing Liu, Chi Luo, John T O'Malley, Ahmed Gehad, Jessica E Teague, Sherrie J Divito, Robert Fuhlbrigge, Pere Puigserver, James G Krueger, Gökhan S Hotamisligil, Rachael A Clark, Thomas S Kupper
Tissue-resident memory T (TRM) cells persist indefinitely in epithelial barrier tissues and protect the host against pathogens. However, the biological pathways that enable the long-term survival of TRM cells are obscure. Here we show that mouse CD8(+) TRM cells generated by viral infection of the skin differentially express high levels of several molecules that mediate lipid uptake and intracellular transport, including fatty-acid-binding proteins 4 and 5 (FABP4 and FABP5). We further show that T-cell-specific deficiency of Fabp4 and Fabp5 (Fabp4/Fabp5) impairs exogenous free fatty acid (FFA) uptake by CD8(+) TRM cells and greatly reduces their long-term survival in vivo, while having no effect on the survival of central memory T (TCM) cells in lymph nodes...
February 20, 2017: Nature
https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#2
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
#3
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/28206973/clinical-implications-of-hla-locus-mismatching-in-unrelated-donor-hematopoietic-cell-transplantation-a-meta-analysis
#4
REVIEW
Ruxiu Tie, Tiansong Zhang, Bo Yang, Huarui Fu, Biqing Han, Jian Yu, Yamin Tan, He Huang
It remains controversial that the impacts of individual HLA locus mismatches on clinical outcomes of patients receiving unrelated-donor hematopoietic cell transplantation (HCT), as compared to HLA allele matched controls. We conducted a meta-analysis to address these issues. Four databases (PubMed, Embase, Web of Science and the Cochrane Library) were searched to select eligible studies. All donor-recipient pairs were high-resolution typing for HLA-A, -B, -C, -DRB1, DQB1 and DPB1 loci. Multivariate-adjusted hazard ratios (HRs) were extracted and pooled using a random-effects model...
February 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28192934/sensitive-approaches-for-the-assay-of-the-global-protein-tyrosine-phosphorylation-in-complex-samples-using-a-mutated-sh2-domain
#5
Yanan Li, Yan Wang, Mingming Dong, Hanfa Zou, Mingliang Ye
Temporal tyrosine phosphorylation (pTyr) plays a crucial role in numerous cellular functions. The characterization of the tyrosine phosphorylation states of cells is of great interest for understanding the underlying mechanisms. In this study, we developed sensitive and cost-effective methods for the assay of the global protein tyrosine phosphorylation in complex samples by using a novel engineered pTyr binding protein, Src SH2 domain triple-point mutant (Trm-SH2). Taking the advantage of the pan-specific interaction of Trm-SH2 to pTyr, a high throughput approach was developed to determine the total protein tyrosine phosphorylation level in a sample...
February 9, 2017: Analytical Chemistry
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
#6
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/28164171/diminished-cd103-%C3%AE-e%C3%AE-7-expression-on-resident-t-cells-from-the-female-genital-tract-of-hiv-positive-women
#7
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/28159905/cutting-edge-tissue-resident-memory-t-cells-generated-by-multiple-immunizations-or-localized-deposition-provide-enhanced-immunity
#8
Brooke Davies, Julia E Prier, Claerwen M Jones, Thomas Gebhardt, Francis R Carbone, Laura K Mackay
Tissue-resident memory T cells (TRM) have been shown to afford superior protection against infection, particularly against pathogens that enter via the epithelial surfaces of the body. Although TRM are often concentrated at sites of prior infection, it has been shown that TRM can disseminate throughout the body. We examined the relative effectiveness of global versus targeted CD8(+) TRM lodgment in skin. The site of initial T cell priming made little difference to skin lodgement, whereas local inflammation and Ag recognition enhanced TRM accumulation and retention...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28125671/relative-telomere-repeat-mass-in-buccal-and-leukocyte-derived-dna
#9
Casey T Finnicum, Conor V Dolan, Gonneke Willemsen, Zachary M Weber, Jason L Petersen, Jeffrey J Beck, Veryan Codd, Dorret I Boomsma, Gareth E Davies, Erik A Ehli
Telomere length has garnered interest due to the potential role it may play as a biomarker for the cellular aging process. Telomere measurements obtained from blood-derived DNA are often used in epidemiological studies. However, the invasive nature of blood draws severely limits sample collection, particularly with children. Buccal cells are commonly sampled for DNA isolation and thus may present a non-invasive alternative for telomere measurement. Buccal and leukocyte derived DNA obtained from samples collected at the same time period were analyzed for telomere repeat mass (TRM)...
2017: PloS One
https://www.readbyqxmd.com/read/28107369/impact-of-donor-activating-kir-genes-on-hsct-outcome-in-c1-ligand-negative-myeloid-disease-patients-transplanted-with-unrelated-donors-a-retrospective-study
#10
Christine Neuchel, Daniel Fürst, Dietger Niederwieser, Donald Bunjes, Chrysanthi Tsamadou, Gerald Wulf, Michael Pfreundschuh, Eva Wagner, Gernot Stuhler, Hermann Einsele, Hubert Schrezenmeier, Joannis Mytilineos
Natural Killer cells (NK) are lymphocytes with the potential to recognize and lyse cells which escaped T-cell mediated lysis due to their aberrant HLA expression profiles. Killer cell immunoglobulin-like receptors (KIR) influence NK-cell activity by mediation of activating or inhibitory signals upon interaction with HLA-C (C1, C2) ligands. Therefore, absence of ligands for donor inhibitory KIRs following hematopoietic stem cell transplantation (HSCT) may have an influence on its outcome. Previous studies showed that C1 negative patients have a decreased HSCT outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28104513/a-multicenter-study-of-bacterial-blood-stream-infections-in-pediatric-allogeneic-hematopoietic-cell-transplantation-recipients-the-role-of-acute-gastrointestinal-graft-versus-host-disease
#11
Prakash Satwani, Jason L Freedman, Sonali Chaudhury, Zhezhen Jin, Anya Levinson, Marc D Foca, Jennifer Krajewski, Indira Sahdev, Mala Kiran Talekar, Aliza Gardenswartz, Justin Silverman, Meghan Hayes, Christopher C Dvorak
Blood stream infections (BSI) caused by enteric organisms are associated with a particularly high mortality rate in allogeneic hematopoietic cell transplantation (alloHCT) recipients. We conducted a retrospective multicenter study aiming to analyze the risk factors associated with antibiotic resistance and impact of BSI on transplantation-related mortality (TRM) in children after alloHCT. During the study period from 2004 to 2014, 395 children (mean age, 9.4 years) with at least 1 BSI were included. The incidences of resistant gram-negative rods were 20...
January 16, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28087457/t-cell-replete-peripheral-blood-haploidentical-hematopoietic-cell-transplantation-with-post-transplantation-cyclophosphamide-results-in-outcomes-similar-to-transplantation-from-traditionally-matched-donors-in-active-disease-acute-myeloid-leukemia
#12
Joan How, Michael Slade, Khoan Vu, John F DiPersio, Peter Westervelt, Geoffrey L Uy, Camille N Abboud, Ravi Vij, Mark A Schroeder, Todd A Fehniger, Rizwan Romee
Outcomes for patients with acute myeloid leukemia (AML) who fail to achieve complete remission remain poor. Hematopoietic cell transplantation (HCT) has been shown to induce long-term survival in AML patients with active disease. HCT is largely performed with HLA-matched unrelated or HLA-matched related donors. Recently, HCT with HLA-haploidentical related donors has been identified as a feasible option when HLA-matched donors are not immediately available. However, there are little data comparing outcomes for AML patients with active disease who receive haploidentical versus traditionally matched HCT...
January 10, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28081153/dermal-%C3%AE-%C3%AE-t-cells-do-not-freely-re-circulate-out-of-skin-and-produce-il-17-to-promote-neutrophil-infiltration-during-primary-contact-hypersensitivity
#13
Xiaodong Jiang, Chang Ook Park, Jenna Geddes Sweeney, Min Jae Yoo, Olivier Gaide, Thomas Seth Kupper
The role of mouse dermal γδ T cells in inflammatory skin disorders and host defense has been studied extensively. It is known that dendritic epidermal T cells (DETC) have a monomorphic γδ T cell receptor (TCR) and reside in murine epidermis from birth. We asked if dermal γδ cells freely re-circulated out of skin, or behaved more like dermal resident memory T cells (TRM) in mice. We found that, unlike epidermal γδ T cells (DETC), dermal γδ cells are not homogeneous with regard to TCR, express the tissue resident T cell markers CD69 and CD103, bear skin homing receptors, and produce IL-17 and IL-22...
2017: PloS One
https://www.readbyqxmd.com/read/28051085/intrinsic-4-1bb-signals-are-indispensable-for-the-establishment-of-an-influenza-specific-tissue-resident-memory-cd8-t-cell-population-in-the-lung
#14
A C Zhou, L E Wagar, M E Wortzman, T H Watts
The induction of long-lived heterotypic T-cell protection against influenza virus remains elusive, despite the conservation of T-cell epitopes. T-cell protection against influenza is critically dependent on lung-resident memory T cells (Trm). Here we show that intranasal administration of 4-1BBL along with influenza nucleoprotein in a replication-defective adenovirus vector to influenza pre-immune mice induces a remarkably stable circulating effector memory CD8 T-cell population characterized by higher IL-7Rα expression than control-boosted T cells, as well as a substantial lung parenchymal CD69(+) CD8 Trm population, including both CD103(+) and CD103(-) cells...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28018970/interlesional-diversity-of-t-cell-receptors-in-melanoma-with-immune-checkpoints-enriched-in-tissue-resident-memory-t-cells
#15
Chandra Sekhar Boddupalli, Noffar Bar, Krishna Kadaveru, Michael Krauthammer, Natopol Pornputtapong, Zifeng Mai, Stephan Ariyan, Deepak Narayan, Harriet Kluger, Yanhong Deng, Rakesh Verma, Rituparna Das, Antonella Bacchiocchi, Ruth Halaban, Mario Sznol, Madhav V Dhodapkar, Kavita M Dhodapkar
Heterogeneity of tumor cells and their microenvironment can affect outcome in cancer. Blockade of immune checkpoints (ICPs) expressed only on a subset of immune cells leads to durable responses in advanced melanoma. Tissue-resident memory T (TRM) cells have recently emerged as a distinct subset of memory T cells in nonlymphoid tissues. Here, we show that functional properties and expression of ICPs within tumor-infiltrating lymphocytes (TILs) differ from those of blood T cells. TILs secrete less IL-2, IFN-γ, and TNF-α compared with circulating counterparts, and expression of VEGF correlated with reduced TIL infiltration...
December 22, 2016: JCI Insight
https://www.readbyqxmd.com/read/28018343/very-late-antigen-1-marks-functional-tumor-resident-cd8-t-cells-and-correlates-with-survival-of-melanoma-patients
#16
Timothy Murray, Silvia A Fuertes Marraco, Petra Baumgaertner, Natacha Bordry, Laurène Cagnon, Alena Donda, Pedro Romero, Grégory Verdeil, Daniel E Speiser
A major limiting factor in the success of immunotherapy is tumor infiltration by CD8(+) T cells, a process that remains poorly understood. In the present study, we characterized homing receptors expressed by human melanoma-specific CD8(+) T cells. Our data reveal that P-selectin binding and expression of the retention integrin, very late antigen (VLA)-1, by vaccine-induced T cells correlate with longer patient survival. Furthermore, we demonstrate that CD8(+)VLA-1(+) tumor-infiltrating lymphocytes (TILs) are highly enriched in melanoma metastases in diverse tissues...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27995879/-comparison-of-allogeneic-or-autologous-hematopoietic-stem-cell-transplant-for-high-risk-peripheral-t-cell-lymphomas
#17
Q L Wang, H W Huang, Z M Jin, X W Tang, H Y Qiu, C C Fu, Y Han, M Miao, H R Chang, A N Sun, D P Wu
Objective: To evaluate the efficacy of auto-HSCT and allo-HSCT in the treatment of high risk peripheral T cell lymphoma (PTCL). Methods: From July 2007 to July 2014, 60 cases of high risk PTCL were analyzed retrospectively. Results: All 60 patients were at high risk group (carried with IPI≥3), with a median age of 31 (12-58) years old. Of the 60 cases, 22 were PTCL-not otherwise specified (PTCL-NOS), 22 ALK negative anaplastic large cell lymphoma (ALK-negative ALCL) and 16 angioimmunoblastic T-cell lymphoma (AITL)...
November 14, 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/27989932/allele-level-hla-matching-impacts-key-outcomes-following-umbilical-cord-blood-transplantation-for-inherited-metabolic-disorders
#18
Kanwaldeep K Mallhi, Angela R Smith, Todd E DeFor, Troy C Lund, Paul J Orchard, Weston P Miller
Allogeneic hematopoietic stem cell transplantation has demonstrated efficacy for numerous inherited metabolic disorders (IMDs). Umbilical cord blood transplant (UCBT) is increasingly used as a graft source in IMDs, but little is known of the impact of cord blood unit (CBU)/recipient HLA allelic disparity on key outcomes following UCBT for IMD. We reviewed outcomes of 106 consecutive first, single UCBTs for IMD at the University of Minnesota with regard to CBU/recipient HLA allelic matching (HLA-A, -B, -C, and -DRB1)...
January 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27987416/tissue-resident-memory-t-cells-and-viral-immunity
#19
REVIEW
Pamela C Rosato, Lalit K Beura, David Masopust
Tissue resident memory T cells (TRM) constitute a recently identified T cell lineage that is responsible for frontline defense against viral infections. In contrast to central and effector memory T cells, which constitutively recirculate between tissues and blood, TRM reside permanently within tissues. As the main surveyors of non-lymphoid tissues, TRM are positioned to rapidly respond upon reinfection at barrier sites. During a viral reinfection, TRM trigger the local tissue environment to activate and recruit immune cells and establish an antiviral state...
December 14, 2016: Current Opinion in Virology
https://www.readbyqxmd.com/read/27941828/metastatic-lymph-node-ratio-demonstrates-better-prognostic-stratification-than-pn-staging-in-patients-with-esophageal-squamous-cell-carcinoma-after-esophagectomy
#20
Hongdian Zhang, Huagang Liang, Yongyin Gao, Xiaobin Shang, Lei Gong, Zhao Ma, Ke Sun, Peng Tang, Zhentao Yu
This study aimed to evaluate the prognostic significance of lymph node ratio (LNR) by establishing a hypothetical tumor-ratio-metastasis (TRM) staging system in patients with esophageal squamous cell carcinoma (ESCC). The records of 387 ESCC patients receiving curative esophagectomy were retrospectively investigated. The optimal cut-point for LNR was assessed via the best cut-off approach. Potential prognostic parameters were identified through univariate and multivariate analyses. A novel LNR-based TRM stage was proposed...
December 12, 2016: Scientific Reports
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