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Costimulatory t cells

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https://www.readbyqxmd.com/read/27914308/regulation-of-t-helper-cell-differentiation-by-e3-ubiquitin-ligases-and-deubiquitinating-enzymes
#1
REVIEW
Si-Fa Gao, Bo Zhong, Dandan Lin
CD4 T cells are essential components of adaptive immunity and play a critical role in anti-pathogenic or anti-tumor responses as well as autoimmune and allergic diseases. Naive CD4 T cells differentiate into distinct subsets of T helper (Th) cells by various signals including TCR, costimulatory and cytokine signals. Accumulating evidence suggests that these signaling pathways are critically regulated by ubiquitination and deubiquitination, two reversible posttranslational modifications mediated by E3 ubiquitin ligases and deubiquitinating enzymes (DUBs), respectively...
November 30, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27913506/checkpoint-inhibition-and-cellular-immunotherapy-in-lymphoma
#2
Premal Lulla, Helen E Heslop
Hodgkin and non-Hodgkin lymphoma are both good targets for immunotherapy, as they are accessible to antibodies and cell-based immunotherapy, express costimulatory molecules, and express lineage-restricted, viral, and unique tumor antigens. Blockade of the programmed-death 1 (PD-1) immune checkpoint has produced very encouraging response rates in patients with Hodgkin lymphoma, whereas adoptive transfer of Epstein-Barr Virus (EBV)-specific T cells has shown clinical activity in patients with posttransplant lymphoma and other EBV-associated lymphomas...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27898464/donor-derived-exosomes-the-trick-behind-the-semidirect-pathway-of-allorecognition
#3
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
#4
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
#5
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
#6
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/27878564/the-role-of-b7-family-costimulatory-molecules-and-indoleamine-2-3-dioxygenase-in-primary-sj%C3%A3-gren-s-syndrome-and-systemic-sclerosis
#7
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
#8
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
#9
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/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/27849617/tethered-il-15-augments-antitumor-activity-and-promotes-a-stem-cell-memory-subset-in-tumor-specific-t-cells
#11
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 29, 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
#12
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...
December 15, 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
#13
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...
December 15, 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
#14
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
#15
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
#16
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
#17
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/27812544/akt-and-shp-1-are-dc-intrinsic-checkpoints-for-tumor-immunity
#18
Yaron Carmi, Tyler R Prestwood, Matthew H Spitzer, Ian L Linde, Jonathan Chabon, Nathan E Reticker-Flynn, Nupur Bhattacharya, Hong Zhang, Xiangyue Zhang, Pamela A Basto, Bryan M Burt, Michael N Alonso, Edgar G Engleman
BM-derived DC (BMDC) are powerful antigen-presenting cells. When loaded with immune complexes (IC), consisting of tumor antigens bound to antitumor antibody, BMDC induce powerful antitumor immunity in mice. However, attempts to employ this strategy clinically with either tumor-associated DC (TADC) or monocyte-derived DC (MoDC) have been disappointing. To investigate the basis for this phenomenon, we compared the response of BMDC, TADC, and MoDC to tumor IgG-IC. Our findings revealed, in both mice and humans, that upon exposure to IgG-IC, BMDC internalized the IC, increased costimulatory molecule expression, and stimulated autologous T cells...
November 3, 2016: JCI Insight
https://www.readbyqxmd.com/read/27812358/induction-of-dendritic-cell-maturation-and-activation-by-a-potential-adjuvant-2-hydroxypropyl-%C3%AE-cyclodextrin
#19
Sun Kyung Kim, Cheol-Heui Yun, Seung Hyun Han
2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) is a chemically modified cyclic oligosaccharide produced from starch that is commonly used as an excipient. Although HP-β-CD has been suggested as a potential adjuvant for vaccines, its immunological properties and mechanism of action have yet to be characterized. In the present study, we investigated the maturation and activation of human dendritic cells (DCs) treated with HP-β-CD. We found that DCs stimulated with HP-β-CD exhibited a remarkable upregulation of costimulatory molecules, MHC proteins, and PD-L1/L2...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27810914/nuclear-calcium-is-required-for-human-t-cell-activation
#20
Sara Monaco, Beate Jahraus, Yvonne Samstag, Hilmar Bading
Calcium signals in stimulated T cells are generally considered single entities that merely trigger immune responses, whereas costimulatory events specify the type of reaction. Here we show that the "T cell calcium signal" is a composite signal harboring two distinct components that antagonistically control genomic programs underlying the immune response. Using human T cells from healthy individuals, we establish nuclear calcium as a key signal in human T cell adaptogenomics that drives T cell activation and is required for signaling to cyclic adenosine monophosphate response element-binding protein and the induction of CD25, CD69, interleukin-2, and γ-interferon...
October 24, 2016: Journal of Cell Biology
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