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https://www.readbyqxmd.com/read/28092803/ox40-structure-and-function-what-questions-remain
#1
REVIEW
Jane Willoughby, Jordana Griffiths, Ivo Tews, Mark S Cragg
OX40 is a type 1 transmembrane glycoprotein, reported nearly 30 years ago as a cell surface antigen expressed on activated T cells. Since its discovery, it has been validated as a bone fide costimulatory molecule for T cells and member of the TNF receptor family. However, many questions still remain relating to its function on different T cell sub-sets and with recent interest in its utility as a target for antibody-mediated immunotherapy, there is a growing need to gain a better understanding of its biology...
January 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28076241/phenotypic-and-functional-characteristics-of-hla-dr-neutrophils-in-brazilians-with-cutaneous-leishmaniasis
#2
Richard E Davis, Smriti Sharma, Jacilara Conceição, Pedro Carneiro, Fernanda Novais, Phillip Scott, Shyam Sundar, Olivia Bacellar, Edgar M Carvalho, Mary E Wilson
The protozoan Leishmania braziliensis causes cutaneous leishmaniasis (CL) in endemic regions. In murine models, neutrophils (PMNs) are recruited to the site of infection soon after parasite inoculation. However, the roles of neutrophils during chronic infection and in human disease remain undefined. We hypothesized that neutrophils help maintain a systemic inflammatory state in subjects with CL. Lesion biopsies from all patients with CL tested contained neutrophils expressing HLA-DR, a molecule thought to be restricted to professional antigen-presenting cells...
October 17, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28069499/precise-manipulation-of-biophysical-particle-parameters-enables-control-of-proinflammatory-cytokine-production-in-presence-of-tlr-3-and-4-ligands
#3
Yoshinori Kakizawa, Jung Seok Lee, Brendan Bell, Tarek M Fahmy
: The biophysical parameters governing nanoparticle (NP)-cell interactions significantly affect biological responses, particularly in the application of NP-based immunotherapeutics. Modulation of the surface biophysical character of NPs can be achieved via introduction of amino acids, which offer the ability to fine tune a range of biophysical parameters of interest. We employed this approach using monodisperse silica NPs coated with numerous poly(amino acid)s (PAAs). The NPs were incubated with dendritic cells (DCs) in conjunction with TLR ligands and production of IL-1β from DCs and IFNγ from T cells primed by these DCs were measured...
January 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28057175/pour-comprendre-l%C3%A2-activation-lymphocytaire-t
#4
Jeanne Galaine, Yann Godet, Olivier Adotévi
T cells activation is a finely regulated process to establish an effective anti-infectious or antitumor immune response while avoiding harmful autoimmune reactions. Although T cells are considered to be the main protagonists of the antitumor immune response, they act in interaction with other immune cells. The meeting of naive T cells with dendritic cells induces their differentiation into effector cells following the recognition of the peptide-MHC complex by the T cell receptor. The interaction of costimulatory molecules present on the surface of T cells with their ligand (s) expressed by mature dendritic cells contribute to the optimal T cell activation and to the formation of the immunological synapse...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28052400/programmed-death-1-ligand-1-and-2-expression-in-cutaneous-squamous-cell-carcinoma-and-their-relationship-with-tumor-infiltrating-dendritic-cells
#5
Qingqing Jiao, Cuiping Liu, Wenzhong Li, Wei Li, Fuming Fang, Qihong Qian, Xueguang Zhang
The Programmed Death-1 (PD-1) receptor ligands, PD-L1 and PD-L2, are costimulatory molecules that contribute to the negative regulation of T-lymphocyte activation. It is still unclear whether there is correlation between PD-L1 or PD-L2 and tumor infiltrating dendritic cells (TIDCs) in cutaneous squamous cell carcinoma (CSCC). The aim of this study was to analyze PD-L1 and PD-L2 expression and dendritic cells (DCs) infiltration in tumor tissue of CSCC patients and investigate their clinical significance. Immunohistochemical analysis was used to evaluate the expression of PD-L1, PD-L2, CD1a, and CD83 in 61 CSCC tissues...
January 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28052311/readapting-the-adaptive-immune-response-therapeutic-strategies-for-atherosclerosis
#6
REVIEW
Andrew P Sage, Ziad Mallat
Cardiovascular diseases remain a major global health issue, with the development of atherosclerosis a major underlying cause. Our treatment of cardiovascular disease has improved greatly over the past 3 decades, but significant need still remains to reduce disease burden. Current priorities include reducing atherosclerosis advancement to clinically significant stages, and preventing plaque rupture or erosion. Inflammation and involvement of the adaptive immune system influences all these aspects and therefore is one focus for future therapeutic development...
January 4, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28026094/phenotypic-characteristics-of-aged-cd4-cd28-null-t-lymphocytes-are-determined-by-changes-in-the-whole-genome-dna-methylation-pattern
#7
Beatriz Suarez-Álvarez, Ramón M Rodríguez, Karin Schlangen, Aroa Baragaño Raneros, Leonardo Márquez-Kisinousky, Agustín F Fernández, Carmen Díaz-Corte, Ana M Aransay, Carlos López-Larrea
Aging is associated with a progressive loss of the CD28 costimulatory molecule in CD4(+) lymphocytes (CD28(null) T cells), which is accompanied by the acquisition of new biological and functional properties that give rise to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset during aging and in several associated inflammatory disorders remain controversial. Here, we present the whole-genome DNA methylation and gene expression profiles of CD28(null) T cells and its CD28(+) counterpart...
December 27, 2016: Aging Cell
https://www.readbyqxmd.com/read/28026044/expression-of-programmed-cell-death-1-and-its-ligand-b7-homolog-1-in-peripheral-blood-lymphocytes-from-patients-with-peripartum-cardiomyopathy
#8
Guozhi Xia, Xiaopu Zheng, Xinye Yao, Xiaowei Yao, Zhongwei Liu, Junkui Wang
BACKGROUND: Immune response has been postulated to play a prominent role in the pathogenesis of peripartum cardiomyopathy (PPCM). Given the importance of programmed death (PD)-1 and its ligand B7 homologue 1 (B7-H1) costimulatory molecules as an immune regulatory pathway, this study aimed to investigate the effect of PD-1 and B7-H1 expression on immune response in peripheral blood lymphocytes from the patients with PPCM. HYPOTHESIS: PD-1 and B7-H1 may be involved in modulating immune response in PPCM...
December 27, 2016: Clinical Cardiology
https://www.readbyqxmd.com/read/28011934/exogenous-il-33-restores-dendritic-cell-activation-and-maturation-in-established-cancer
#9
Donye Dominguez, Cong Ye, Zhe Geng, Siqi Chen, Jie Fan, Lei Qin, Alan Long, Long Wang, Zhuoli Zhang, Yi Zhang, Deyu Fang, Timothy M Kuzel, Bin Zhang
The role of IL-33, particularly in tumor growth and tumor immunity, remains ill-defined. We show that exogenous IL-33 can induce robust antitumor effect through a CD8(+) T cell-dependent mechanism. Systemic administration of rIL-33 alone was sufficient to inhibit growth of established tumors in transplant and de novo melanoma tumorigenesis models. Notably, in addition to a direct action on CD8(+) T cell expansion and IFN-γ production, rIL-33 therapy activated myeloid dendritic cells (mDCs) in tumor-bearing mice, restored antitumor T cell activity, and increased Ag cross-presentation within the tumor microenvironment...
December 23, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28011265/involvement-of-ly6c-4-1bb-and-klrg1-in-the-activation-of-lamina-propria-lymphocytes-in-the-small-intestine-of-sanroque-mice
#10
Dina Montufar-Solis, Alexander Williams, Nadarajah Vigneswaran, John R Klein
Roquin is an E3 ligase that regulates mRNA stability. Mice with a mutation in the Rc3h1 gene and Roquin protein, referred to as Roquin(san/san) or sanroque mice, develop broad-spectrum chronic inflammatory conditions and autoimmune pathologies. Our laboratory recently reported that sanroque mice also develop extensive inflammation that is localized in the small intestine but is rare in the colon. Here, we demonstrate that small intestinal intraepithelial lymphocytes (IELs) are present in the epithelium of sanroque mice but that cell recoverability is low using standard extraction techniques even though lamina propria lymphocytes (LPLs) can be recovered in normal numbers...
December 21, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28002569/protective-role-of-icos-and-icos-ligand-in-corneal-transplantation-and-in-maintenance-of-immune-privilege
#11
Tomoyuki Kunishige, Hiroko Taniguchi, Misao Terada, Hisaya Akiba, Hideo Yagita, Ryo Abe, Junko Hori
Purpose: The interaction between the inducible costimulatory molecule (ICOS) and ICOS ligand (ICOSL) has been implicated in the differentiation and functions of T cells. The purpose of the present study was to determine the role of ICOS-ICOSL in the immune privilege of corneal allografts. Methods: Expression of ICOS and ICOSL mRNA from mouse eyes was assessed by RT-PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of ICOS-/- BALB/c recipients and BALB/c wild-type (WT) recipients treated with anti-ICOSL mAb, and graft survival was assessed...
December 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27984277/impact-of-hyperlipidemia-on-alloimmunity
#12
Jessamyn Bagley, Jin Yuan, John Iacomini
PURPOSE OF REVIEW: Hyperlipidemia is a comorbidity affecting a significant number of transplant patients despite treatment with cholesterol lowering drugs. Recently, it has been shown that hyperlipidemia can significantly alter T-cell responses to cardiac allografts in mice, and graft rejection is accelerated in dyslipidemic mice. Here, we review recent advances in our understanding of hyperlipidemia in graft rejection. RECENT FINDINGS: Hyperlipidemic mice have significant increases in serum levels of proinflammatory cytokines, and neutralization of interleukin 17 (IL-17) slows graft rejection, suggesting that IL-17 production by Th17 cells was necessary but not sufficient for rejection...
February 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27978489/structural-mutational-and-biophysical-studies-reveal-a-canonical-mode-of-molecular-recognition-between-immune-receptor-tigit-and-nectin-2
#13
Dibyendu Samanta, Haisu Guo, Rotem Rubinstein, Udupi A Ramagopal, Steven C Almo
In addition to antigen-specific stimulation of T cell receptor (TCR) by a peptide-MHC complex, the functional outcome of TCR engagement is regulated by antigen-independent costimulatory signals. Costimulatory signals are provided by an array of interactions involving activating and inhibitory receptors expressed on T cells and their cognate ligands on antigen presenting cells. T cell immunoglobulin and ITIM domain (TIGIT), a recently identified immune receptor expressed on T and NK cells, upon interaction with either of its two ligands, nectin-2 or poliovirus receptor (PVR), inhibits activation of T and NK cells...
January 2017: Molecular Immunology
https://www.readbyqxmd.com/read/27932157/belatacept-and-eculizumab-for-treatment-of-calcineurin-inhibitor-induced-thrombotic-microangiopathy-after-kidney-transplantation-case-report
#14
J Merola, P S Yoo, J Schaub, J D Smith, M I Rodriguez-Davalos, E Tichy, D C Mulligan, W Asch, R Formica, M Kashgarian, S Kulkarni
Thrombotic microangiopathy (TMA) after kidney transplantation is an uncommon and challenging cause of graft dysfunction and is associated with early graft loss. An idiosyncratic endothelial reaction to calcineurin inhibitors (CNIs) has been implicated as a frequent cause of TMA. This reaction is marked by uncontrolled activation of complement and subsequent cellular destruction. Usual therapy consists of withdrawal of the inciting drug and plasmapheresis to minimize levels of circulating complement. Recently, eculizumab, a monoclonal antibody to complement component C5, has been used for the treatment of atypical hemolytic uremic syndrome...
November 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931590/cytotoxic-t-lymphocyte-associated-protein-4-acts-on-local-draining-lymph-nodes-in-the-allogeneic-abdominal-skin-flap-of-a-rat-model-to-extend-its-survival
#15
G Ma, J Pei, Y Li, Y Han, D Liu
BACKGROUND: Early acute allograft rejection is the result of immune cells mainly composed of thymocyte (T) cells, which are activated, mature, and differentiate in lymphoid tissue. METHODS: Cytotoxic T lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) competitively suppresses the cluster of differentiation 28/CTLA4-B7 costimulatory signaling pathway and alters the ratio of T helper 1 to T helper 2, leading to the inhibition of T cell activation. RESULTS: We used lentivirus-packed CTLA4-Ig to infect the local draining lymph nodes of the allograft skin flap in a rat model, which effectively extended the survival of the allograft...
December 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27914308/regulation-of-t-helper-cell-differentiation-by-e3-ubiquitin-ligases-and-deubiquitinating-enzymes
#16
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...
January 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27913506/checkpoint-inhibition-and-cellular-immunotherapy-in-lymphoma
#17
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
#18
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...
February 2017: 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
#19
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...
January 1, 2017: 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
#20
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...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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