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https://www.readbyqxmd.com/read/27898464/donor-derived-exosomes-the-trick-behind-the-semidirect-pathway-of-allorecognition
#1
Adrian E Morelli, William Bracamonte-Baran, William J Burlingham
PURPOSE OF REVIEW: The passenger leukocyte hypothesis predicts that after transplantation, donor antigen-presenting cells (APCs) from the graft present donor MHC molecules to directly alloreactive T cells in lymphoid organs. However, in certain transplantation models, recent evidence contradicts this long-standing concept. New findings demonstrate that host, instead of donor, APCs play a prominent role in allosensitization against donor MHC molecules via the semidirect pathway. A similar mechanism operates in development of T-cell split tolerance to noninherited maternal antigens...
November 24, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27895177/ox40-cooperates-with-icos-to-amplify-follicular-th-cell-development-and-germinal-center-reactions-during-infection
#2
Vikas Tahiliani, Tarun E Hutchinson, Georges Abboud, Michael Croft, Shahram Salek-Ardakani
Cognate interactions between T follicular helper (Tfh) cells and B cells are essential for promoting protective Ab responses. Whereas costimulatory receptors such as ICOS are accepted as being important for the induction of Tfh cell fate decision, other molecules may play key roles in amplifying or maintaining the Tfh phenotype. In this study, with vaccinia virus infection in mice, we show that OX40 was expressed on Tfh cells that accumulated at the T/B borders in the white pulp of the spleen and that OX40-dependent signals directly shaped the magnitude and quality of the their response to viral Ags...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27895174/human-lung-fibroblasts-present-bacterial-antigens-to-autologous-lung-th-cells
#3
Andrew J Hutton, Marta E Polak, C Mirella Spalluto, Joshua C Wallington, Chris Pickard, Karl J Staples, Jane A Warner, Tom M A Wilkinson
Lung fibroblasts are key structural cells that reside in the submucosa where they are in contact with large numbers of CD4(+) Th cells. During severe viral infection and chronic inflammation, the submucosa is susceptible to bacterial invasion by lung microbiota such as nontypeable Haemophilus influenzae (NTHi). Given their proximity in tissue, we hypothesized that human lung fibroblasts play an important role in modulating Th cell responses to NTHi. We demonstrate that fibroblasts express the critical CD4(+) T cell Ag-presentation molecule HLA-DR within the human lung, and that this expression can be recapitulated in vitro in response to IFN-γ...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27895172/pulmonary-dendritic-cell-subsets-shape-the-respiratory-syncytial-virus-specific-cd8-t-cell-immunodominance-hierarchy-in-neonates
#4
Allison M W Malloy, Tracy J Ruckwardt, Kaitlyn M Morabito, Annie W Lau-Kilby, Barney S Graham
Young infants are generally more susceptible to viral infections and experience more severe disease than do adults. CD8(+) T cells are important for viral clearance, and although often ineffective in neonates they can be protective when adequately stimulated. Using a murine CB6F1/J hybrid model of respiratory syncytial virus (RSV) infection, we previously demonstrated that the CD8(+) T cell immunodominance hierarchy to two RSV-derived epitopes, K(d)M282-90 and D(b)M187-195, was determined by the age at infection...
November 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27887866/continuously-expanding-car-nk-92-cells-display-selective-cytotoxicity-against-b-cell-leukemia-and-lymphoma
#5
Sarah Oelsner, Miriam E Friede, Congcong Zhang, Juliane Wagner, Susanne Badura, Peter Bader, Evelyn Ullrich, Oliver G Ottmann, Hans Klingemann, Torsten Tonn, Winfried S Wels
BACKGROUND AIMS: Natural killer (NK) cells can rapidly respond to transformed and stressed cells and represent an important effector cell type for adoptive immunotherapy. In addition to donor-derived primary NK cells, continuously expanding cytotoxic cell lines such as NK-92 are being developed for clinical applications. METHODS: To enhance their therapeutic utility for the treatment of B-cell malignancies, we engineered NK-92 cells by lentiviral gene transfer to express chimeric antigen receptors (CARs) that target CD19 and contain human CD3ζ (CAR 63...
November 22, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27878564/the-role-of-b7-family-costimulatory-molecules-and-indoleamine-2-3-dioxygenase-in-primary-sj%C3%A3-gren-s-syndrome-and-systemic-sclerosis
#6
Nóra Legány, László Berta, László Kovács, Attila Balog, Gergely Toldi
B7 costimulatory molecules are present on antigen-presenting cells (APCs) and influence intracellular expression of indoleamine 2,3-dioxygenase (IDO), a molecule with important immunoregulatory functions. We determined the frequency of activated (CD11b+) monocytes expressing B7-1, B7-2, B7-H1, and B7-H2 molecules, and that of CD3+ and CD4+ T cells expressing the corresponding CD28, CTLA-4, PD-1, and ICOS receptors in peripheral blood samples of 20 healthy adults and 9 SSc and 15 pSS patients using flow cytometry...
November 23, 2016: Immunologic Research
https://www.readbyqxmd.com/read/27878306/effects-of-interleukin-1-receptor-associated-kinase%C3%A2-1-rna-interference-in-dendritic-cells-on-inflammatory-cytokine-release-and-t-cell-proliferation
#7
Yan Gao, Xuxu Xu, Juan Feng, Ying Ma, Dongming Zheng, Yiming Meng, Fengping Shan
The present study aimed to reduce the expression of interleukin-1 receptor-associated kinase 1 (IRAK-1) in dendritic cells (DCs) by RNA interference (RNAi). Subsequently, its effects on the expression of costimulatory surface molecules, the release of inflammatory cytokines, and the proliferation of T cells during the activation process of DCs, were determined. RNAi was used to silence IRAK‑1 gene expression in DCs, followed by lipopolysaccharide stimulation. Flow cytometry was then used to detect the expression levels of DC surface molecules, including cluster of differentiation (CD)86, major histocompatibility complex class II and CD40...
November 15, 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27869196/t-cell-stimuli-independently-sum-to-regulate-an-inherited-clonal-division-fate
#8
J M Marchingo, G Prevedello, A Kan, S Heinzel, P D Hodgkin, K R Duffy
In the presence of antigen and costimulation, T cells undergo a characteristic response of expansion, cessation and contraction. Previous studies have revealed that population-level reproducibility is a consequence of multiple clones exhibiting considerable disparity in burst size, highlighting the requirement for single-cell information in understanding T-cell fate regulation. Here we show that individual T-cell clones resulting from controlled stimulation in vitro are strongly lineage imprinted with highly correlated expansion fates...
November 21, 2016: Nature Communications
https://www.readbyqxmd.com/read/27867516/autoantibodies-against-cd80-in-patients-with-copd
#9
Xu Min Luo, Xin Yan Liu, Ji Hong Tang, Wei Yang, Zhen Hua Ni, Qing Ge Chen, Xiongbiao Wang
Chronic obstructive pulmonary disease (COPD) is an inflammation disorder and possibly an autoimmune disease. The components of the autoimmune response in the circulatory system are of considerable interest to clinicians. Because aberrations of costimulation status have been noted in COPD, the presence of autoantibodies to B7 costimulatory factor CD80 were investigated in a cohort of patients. Recombinant rs1CD80 (lacking the transmembrane domain of CD80) was used for Western blot analysis and ELISA to investigate the presence of autoantibodies in sera of patients with stable COPD and in controls without COPD...
October 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/27859053/b-cell-intrinsic-function-of-tapp-adaptors-in-controlling-germinal-center-responses-and-autoantibody-production-in-mice
#10
Nipun Jayachandran, Ivan Landego, Sen Hou, Dario R Alessi, Aaron J Marshall
Control of B-cell signal transduction is critical to prevent production of pathological autoantibodies. Tandem PH domain containing proteins (TAPPs) specifically bind PI(3,4)P2, a phosphoinositide product generated by PI 3-kinases and the phosphatase SHIP. TAPP KI mice bearing PH domain-inactivating mutations in both TAPP1 and TAPP2 genes, uncoupling them from PI(3,4)P2, exhibit increased BCR-induced activation of the kinase Akt and develop lupus-like characteristics including anti-DNA antibodies and deposition of immune complexes in kidneys...
November 15, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27855374/inflammatory-properties-and-adjuvant-potential-of-synthetic-glycolipids-homologous-to-mycolate-esters-of-the-cell-wall-of-mycobacterium-tuberculosis
#11
Hermann Giresse Tima, Juma''a Raheem Al Dulayymi, Olivier Denis, Pauline Lehebel, Klarah Sherzad Baols, Mohsin Omar Mohammed, Laurent L'Homme, Mohaned Mohammed Sahb, Georges Potemberg, Sylvie Legrand, Roland Lang, Rudi Beyaert, Jacques Piette, Mark Stephen Baird, Kris Huygen, Marta Romano
The cell wall of mycobacteria is characterised by glycolipids composed of different classes of mycolic acids (MAs; alpha-, keto-, and methoxy-) and sugars (trehalose, glucose, and arabinose). Studies using mutant Mtb strains have shown that the structure of MAs influences the inflammatory potential of these glycolipids. As mutant Mtb strains possess a complex mixture of glycolipids, we analysed the inflammatory potential of single classes of mycolate esters of the Mtb cell wall using 38 different synthetic analogues...
November 18, 2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27849617/tethered-il-15-augments-antitumor-activity-and-promotes-a-stem-cell-memory-subset-in-tumor-specific-t-cells
#12
Lenka V Hurton, Harjeet Singh, Amer M Najjar, Kirsten C Switzer, Tiejuan Mi, Sourindra Maiti, Simon Olivares, Brian Rabinovich, Helen Huls, Marie-Andrée Forget, Vrushali Datar, Partow Kebriaei, Dean A Lee, Richard E Champlin, Laurence J N Cooper
Adoptive immunotherapy retargeting T cells to CD19 via a chimeric antigen receptor (CAR) is an investigational treatment capable of inducing complete tumor regression of B-cell malignancies when there is sustained survival of infused cells. T-memory stem cells (TSCM) retain superior potential for long-lived persistence, but challenges exist in manufacturing this T-cell subset because they are rare among circulating lymphocytes. We report a clinically relevant approach to generating CAR(+) T cells with preserved TSCM potential using the Sleeping Beauty platform...
November 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27837111/age-associated-b-cells-with-proinflammatory-characteristics-are-expanded-in-a-proportion-of-multiple-sclerosis-patients
#13
Nele Claes, Judith Fraussen, Marjan Vanheusden, Niels Hellings, Piet Stinissen, Bart Van Wijmeersch, Raymond Hupperts, Veerle Somers
Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgD(-)CD27(-) (double negative, DN) and CD21(-)CD11c(+) (CD21(low)) B cells were described as age-associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21(low) B cells in multiple sclerosis (MS) patients. Using flow cytometry, we demonstrated a higher proportion of MS patients younger than 60 y with peripheral expansions of DN (8/41) and CD21(low) (9/41) B cells compared with age-matched healthy donors (1/33 and 2/33, respectively), which indicates an increase in age-associated B cells in MS patients...
November 11, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27837108/characterization-and-transcriptomic-analysis-of-porcine-blood-conventional-and-plasmacytoid-dendritic-cells-reveals-striking-species-specific-differences
#14
Gael Auray, Irene Keller, Sylvie Python, Markus Gerber, Remy Bruggmann, Nicolas Ruggli, Artur Summerfield
Porcine dendritic cells (DCs) are relatively well characterized, but a clear-cut identification of all DC subsets combined with full transcriptional profiling was lacking, preventing an unbiased insight into the functional specializations of DC subsets. Using a large panel of Abs in multicolor flow cytometry, cell sorting, and RNA sequencing we identified and characterized the porcine equivalent of conventional DCs (cDC) 1 and cDC2 as well as plasmacytoid DCs (pDCs) in the peripheral blood of pigs. We demonstrate that cDC1 are CD135(+)CD14(-)CD172a(low)CADM1(+)wCD11R1(+) cells, cDC2 are CD135(+)CD14(-)CD172a(+)CADM1(+)CD115(+)wCD11R1(+)CD1(+) cells and pDCs are CD4(+)CD135(+)CD172a(+)CD123(+)CD303(+) cells...
November 11, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27837103/dendritic-cell-klf2-expression-regulates-t-cell-activation-and-proatherogenic-immune-responses
#15
Noah Alberts-Grill, Daniel Engelbertsen, Dexiu Bu, Amanda Foks, Nir Grabie, Jan M Herter, Felicia Kuperwaser, Tao Chen, Gina Destefano, Petr Jarolim, Andrew H Lichtman
Dendritic cells (DCs) have been implicated as important regulators of innate and adaptive inflammation in many diseases, including atherosclerosis. However, the molecular mechanisms by which DCs mitigate or promote inflammatory pathogenesis are only partially understood. Previous studies have shown an important anti-inflammatory role for the transcription factor Krüppel-like factor 2 (KLF2) in regulating activation of various cell types that participate in atherosclerotic lesion development, including endothelial cells, macrophages, and T cells...
November 11, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27835062/class-i-restricted-t-cell-associated-molecule-is-a-marker-for-ifn-%C3%AE-producing-inkt-cells-in-healthy-subjects-and-patients-with-type-1-diabetes
#16
Nonantzin Beristain-Covarrubias, Elsy B Canche-Pool, Carlos Ramirez-Velazquez, Juan Carlos Barragan-Galvez, Rita A Gomez-Diaz, Vianney Ortiz-Navarrete
Class I-restricted T cell-associated molecule (CRTAM) is an activation marker expressed on the cell surface of activated invariant natural killer T (iNKT) cells, CD8(+) T cells, and a small subset of CD4(+) T cells. CRTAM has also been associated with a proinflammatory profile in murine CD4(+) T cells. However, CRTAM has not been thoroughly explored in human cells. This work focused on evaluating CRTAM expression in human iNKT lymphocytes after activation with α-galactosylceramide, its widely used specific glycolipid antigen...
November 11, 2016: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/27827885/is-there-still-room-for-cancer-vaccines-at-the-era-of-checkpoint-inhibitors
#17
REVIEW
Soumaya Karaki, Marie Anson, Thi Tran, Delphine Giusti, Charlotte Blanc, Stephane Oudard, Eric Tartour
Checkpoint inhibitor (CPI) blockade is considered to be a revolution in cancer therapy, although most patients (70%-80%) remain resistant to this therapy. It has been hypothesized that only tumors with high mutation rates generate a natural antitumor T cell response, which could be revigorated by this therapy. In patients with no pre-existing antitumor T cells, a vaccine-induced T cell response is a rational option to counteract clinical resistance. This hypothesis has been validated in preclinical models using various cancer vaccines combined with inhibitory pathway blockade (PD-1-PDL1-2, CTLA-4-CD80-CD86)...
November 3, 2016: Vaccines
https://www.readbyqxmd.com/read/27822406/pd-1-inhibition-and-treatment-of-advanced-melanoma-role-of-pembrolizumab
#18
REVIEW
Ali R Jazirehi, Alexandra Lim, Tam Dinh
Remarkable clinical responses have been seen in patients with metastatic melanoma with targeted therapy (BRAFi vemurafenib, MEKi) and with modern immune cell-based approaches such as TCR engineered adoptive cell transfer (ACT) and earlier experiences with high-dose IL-2. The proximal mediators of these immune therapies are tumor-reactive CTL. Various mechanisms of resistance to immune-mediated apoptotic signals have been described, including phenotypic changes, effector cell exhaustion, functional tolerance, deficiencies in Ag processing and presentation, and mutation or down-regulation of antigenic epitopes...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27815442/vegf-requires-the-receptor-nrp-1-to-inhibit-lipopolysaccharide-dependent-dendritic-cell-maturation
#19
Nougboli A E Oussa, Amina Dahmani, Marie Gomis, Manon Richaud, Emil Andreev, Ali-Reza Navab-Daneshmand, Julie Taillefer, Cédric Carli, Salix Boulet, Laurent Sabbagh, Nathalie Labrecque, Przemyslaw Sapieha, Jean-Sébastien Delisle
To stimulate a productive T cell response, dendritic cells (DC) must undergo maturation characterized by heightened cell surface expression of MHC and costimulatory molecules as well as cytokine production. Conversely, the inhibition of DC maturation is a central mechanism of immune tolerance. The control of the DC maturation process relies on the integration of several cellular stimulatory or inhibitory signals. The soluble factors and their receptors controlling this central aspect of DC biology are incompletely characterized...
November 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27812661/expression-of-co-stimulatory-molecules-cd80-and-cd86-is-altered-in-cd14-hla-dr-monocytes-from-patients-with-chagas-disease-following-induction-by-trypanosoma-cruzi-recombinant-antigens
#20
Ana Karine de Araújo Soares, Patrícia Areias Feitosa Neves, Maria da Glória Aureliano de Melo Cavalcanti, Sílvia Martins Marinho, Wilson de Oliveira, Joelma Rodrigues de Souza, Virginia Maria Barros de Lorena, Yara de Miranda Gomes
INTRODUCTION: The relationships between monocytes and lymphocytes through MHC class II molecules and costimulatory, are of utmost importance for the production of an efficient immune response. In this work, we assessed the expression of surface molecules CD80 and CD86 on CD14+HLA-DR+ monocytes from patients with Chagas disease. METHODS: The study population consisted of 31 patients with chronic clinical forms of Chagas disease. Patient blood samples were cultured in the presence of recombinant cytoplasmic repetitive antigen (CRA) and flagellar repetitive antigen (FRA)...
September 2016: Revista da Sociedade Brasileira de Medicina Tropical
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