Read by QxMD icon Read

Costimulatory t cells

Qiong Liu, Wen Wen, Liang Tang, Chen-Jie Qin, Yan Lin, Hui-Lu Zhang, Han Wu, Charles Ashton, Hong-Ping Wu, Jin Ding, Wei Dong, Le-Xing Yu, Wen Yang, Dan-Dan Huang, Meng-Chao Wu, Hong-Yang Wang, He-Xin Yan
Despite their central function in tumor immunity, dendritic cells (DCs) can respond to inhibitory signals and become tolerogenic, curtailing T cell responses in vivo. Here, we provide the evidence for an inhibitory function of signal regulatory protein (SIRP) α in DC survival and activation. In tumors from human liver cancer patients, infiltrative DCs expressed elevated levels of SIRPα, which is correlated with the induction of immune tolerance within the tumors. Silencing of SIRPα resulted in a significant increase in the longevity of antigen-pulsed DCs in the draining lymph nodes...
2016: Oncoimmunology
Hirotsugu Nagase, Tomohira Takeoka, Shinya Urakawa, Akiko Morimoto-Okazawa, Atsunari Kawashima, Kota Iwahori, Shuji Takiguchi, Hiroyoshi Nishikawa, Eiichi Sato, Shimon Sakaguchi, Masaki Mori, Yuichiro Doki, Hisashi Wada
Regulatory T cells (Tregs) have an immunosuppressive role in the tumor microenvironment. Since effector Tregs (eTregs), which have highly suppressive functions, are located in a subpopulation of Foxp3(+) CD4(+) Tregs, the TCR-inducible costimulatory receptor (ICOS) was applied as a marker of eTregs that infiltrated gastric cancer tissue and the induction pathway of ICOS(+) Foxp3(+) cells was analyzed by flow cytometry and immunohistochemistry. In tumor-infiltrating lymphocytes (TILs), ICOS(+) Foxp3(+) CD4(+) T cells were abundantly observed in the late stages of gastric cancer...
October 18, 2016: International Journal of Cancer. Journal International du Cancer
Susmita K Singh, Anna-Maria Andersson, Rada Ellegård, Cecilia S Lindestam Arlehamn, Alessandro Sette, Marie Larsson, Olle Stendahl, Robert Blomgran
HIV coinfection is the most prominent risk factor for progression of Mycobacterium tuberculosis (Mtb) infection into active tuberculosis (TB) disease. The mechanisms behind the increased transition from latent to active TB in coinfected individuals have not been well elucidated at the cellular level. We hypothesized that HIV infection contributes to Mtb pathogenesis by interfering with the dendritic cell (DC)-mediated immune control. Mtb-antigen processing and presentation are key events in the immune response against TB...
October 13, 2016: American Journal of Pathology
Herman Waldmann, Duncan Howie, Stephen Cobbold
A major goal of immunosuppressive therapies is to harness immune tolerance mechanisms so as to minimize unwanted side effects associated with protracted immunosuppressive therapy. Antibody blockade of lymphocyte coreceptor and costimulatory pathways in mice has demonstrated the principle that both naive and primed immune systems can be reprogrammed toward immunological tolerance. Such tolerance can involve the amplification of activity of regulatory T cells, and is maintained through continuous recruitment of such cells through processes of infectious tolerance...
August 2016: Microbiology Spectrum
Hengling Cai, Shenghua Chen, Sha Xu, Yuanbin Sun, Qinqin Bai, Chunxue Lu, Yuyu Chen, Xizong Fu, Guilian Xu, Lili Chen
LIGHT, a costimulatory member of the immunoglobulin superfamily (Ig SF), can greatly impact T cell activation. The role of the LIGHT signaling pathway in chlamydial infection was evaluated in mice following respiratory tract infection with Chlamydia psittaci. Compared with wild type (WT) mice, LIGHT knockout (KO) mice showed significant reduction of body weight, much lower survival rate, higher bacterial burden, prolonged infection time courses and more severe pathological changes in lung tissue. The mRNA levels of IFN-γ, TNF-α, IL-17 and IL-12 in the lung tissue of LIGHT KO mice were significantly lower than those in WT mice...
October 8, 2016: Microbial Pathogenesis
Judith Fraussen, Nele Claes, Bart Van Wijmeersch, Jack van Horssen, Piet Stinissen, Raymond Hupperts, Veerle Somers
Antibody-independent B cell functions play an important role in multiple sclerosis (MS) pathogenesis. In this study, B cell antigen presentation and costimulation in MS were studied. Peripheral blood B cells of MS patients showed increased expression of costimulatory CD86 and CD80 molecules compared with healthy controls (HC). In MS cerebrospinal fluid (CSF), 12-fold and 2-fold increases in CD86(+) and CD80(+) B cells, respectively, were evidenced compared with peripheral blood. Further, B cells from MS patients induced proinflammatory T cells in response to myelin basic protein (MBP)...
October 4, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Revital Levy, Ziv Rotfogel, Dalia Hillman, Andrey Popugailo, Gila Arad, Emmanuelle Supper, Farhat Osman, Raymond Kaempfer
Full T-cell activation requires interaction between the costimulatory receptors B7-2 and CD28. By binding CD28, bacterial superantigens elicit harmful inflammatory cytokine overexpression through an unknown mechanism. We show that, by engaging not only CD28 but also its coligand B7-2 directly, superantigens potently enhance the avidity between B7-2 and CD28, inducing thereby T-cell hyperactivation. Using the same 12-aa β-strand-hinge-α-helix domain, superantigens engage both B7-2 and CD28 at their homodimer interfaces, areas remote from where these coreceptors interact, implying that inflammatory signaling can be controlled through the receptor homodimer interfaces...
October 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Suelen Martins Perobelli, Ana Carolina Terra Mercadante, Rômulo Gonçalves Galvani, Triciana Gonçalves-Silva, Ana Paula Gregório Alves, Antonio Pereira-Neves, Marlene Benchimol, Alberto Nóbrega, Adriana Bonomo
Acute graft-versus-host disease (aGVHD) is the main complication of allogeneic hematopoietic stem cell transplantation, and many efforts have been made to overcome this important limitation. We showed previously that G-CSF treatment generates low-density splenic granulocytes that inhibit experimental aGVHD. In this article, we show that aGVHD protection relies on incoming IL-10(+) neutrophils from G-CSF-treated donor spleen (G-Neutrophils). These G-Neutrophils have high phagocytic capacity, high peroxide production, low myeloperoxidase activity, and low cytoplasmic granule content, which accounts for their low density...
October 5, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Sara Tanaskovic, Patricia Price, Martyn A French, Sonia Fernandez
HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency often retain low CD4<sup>+</sup> T-cell counts despite virological control. We examined proliferative responses and upregulation of costimulatory molecules following anti-CD3 stimulation, in HIV patients with persistent CD4<sup>+</sup> T-cell deficiency on ART. Aviraemic HIV patients with nadir CD4<sup>+</sup> T-cell counts <100 cells/μl who had received ART for a median time of 7 (range 1-11) years were categorized into those achieving low (<350 cells/μL; n=13) or normal (>500 cells/μL; n=20) CD4<sup>+</sup> T-cell counts...
October 5, 2016: AIDS Research and Human Retroviruses
Yuriko Itzel Sánchez-Zamora, Imelda Juarez-Avelar, Alicia Vazquez-Mendoza, Marcia Hiriart, Miriam Rodriguez-Sosa
Macrophage migration inhibitory factor (Mif) is highly expressed in type 1 diabetes mellitus (T1DM). However, there is limited information about how Mif influences the activation of macrophages (Mφ) and dendritic cells (DC) in T1DM. To address this issue, we induced T1DM by administering multiple low doses of streptozotocin (STZ) to Mif-/- or wild-type (Wt) BALB/c mice. We found that Mif-/- mice treated with STZ (Mif-/-STZ) developed lower levels of hyperglycemia, inflammatory cytokines, and specific pancreatic islet antigen- (PIAg-) IgG and displayed reduced cellular infiltration into the pancreatic islets compared to Wt mice treated with STZ (WtSTZ)...
2016: Journal of Diabetes Research
Julien Leconte, Sahar Bagherzadeh Yazdchi, Vincent Panneton, Woong-Kyung Suh
The inducible costimulator (ICOS) is a T cell costimulatory receptor that plays crucial roles in T cell differentiation and function. So far, ICOS has been shown to activate three signaling components: phosphoinositide 3-kinase (PI3K), intracellular calcium mobilization, and TANK binding kinase 1 (TBK1). By generating a knock-in strain of mice in which the ICOS gene is modified such that the ICOS-mediated PI3K pathway is selectively abrogated while the capacity of ICOS to mobilize intracellular calcium remains intact, we have shown that ICOS-mediated PI3K activation is required for some but not all T cell responses...
September 29, 2016: Molecular Immunology
Emre Balta, Julian Stopp, Laura Castelletti, Henning Kirchgessner, Yvonne Samstag, Guido H Wabnitz
Neutrophils or polymorphonuclear cells (PMN) eliminate bacteria via phagocytosis and/or NETosis. Apart from these conventional roles, PMN also have immune-regulatory functions. They can transdifferentiate and upregulate MHCII as well as ligands for costimulatory receptors which enables them to behave as antigen presenting cells (APC). The initial step for activating T-cells is the formation of an immune synapse between T-cells and antigen-presenting cells). However, the immune synapse that develops at the PMN/T-cell contact zone is as yet hardly investigated due to the non-availability of methods for analysis of large number of PMN interactions...
September 27, 2016: Methods: a Companion to Methods in Enzymology
Kae Won Cho, Brian F Zamarron, Lindsey A Muir, Kanakadurga Singer, Cara E Porsche, Jennifer B DelProposto, Lynn Geletka, Kevin A Meyer, Robert W O'Rourke, Carey N Lumeng
Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDCs), contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we use CD64 to distinguish ATM and ATDC, and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80(+)CD11b(+) cells overlaps with other leukocytes and that CD45(+)CD64(+) is specific for ATM...
September 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Inge Kepert, Juliano Fonseca, Constanze Müller, Katrin Milger, Kerstin Hochwind, Matea Kostric, Maria Fedoseeva, Caspar Ohnmacht, Stefan Dehmel, Petra Nathan, Sabine Bartel, Oliver Eickelberg, Michael Schloter, Anton Hartmann, Philippe Schmitt-Kopplin, Susanne Krauss-Etschmann
BACKGROUND: Chronic immune diseases (CIDs), such as asthma, are highly prevalent. Currently available pharmaceuticals improve symptoms, but cannot cure the disease. This prompted demands for alternatives to pharmaceuticals such as probiotics for prevention of allergic disease. However, clinical trials have given inconsistent results. This is at least partly explained by the highly complex crosstalk among probiotic bacteria, the host´s microbiota, and immune cells. The identification of a bioactive substance from probiotic bacteria could circumvent this difficulty...
September 23, 2016: Journal of Allergy and Clinical Immunology
Wataru Amano, Saeko Nakajima, Yasuo Yamamoto, Atsuo Tanimoto, Mutsuyoshi Matsushita, Yoshiki Miyachi, Kenji Kabashima
BACKGROUND: Using JAK inhibitors to inhibit cytokine signaling is presumed to be a possible means of treating skin inflammatory disorders such as contact dermatitis. OBJECTIVE: To clarify the action site of JAK inhibitors in skin inflammatory disorders. METHODS: We analyzed the mechanism of action of the JAK inhibitor JTE-052 using murine skin inflammation models, including contact hypersensitivity (CHS) and irritant contact dermatitis. Cells isolated from ear tissue or lymph node (LN) were analyzed by flow cytometry...
September 13, 2016: Journal of Dermatological Science
Shinsuke Oshima, Yasutomo Fujii, Erik E Karrer, Fujiko Takamura, Steven J Chapin, Margaret Neighbors, Sridhar Viswanathan, Bruce H Devens, Yasuyuki Higashi, Hidekazu Mizuhara
The CTLA4-Ig fusion proteins abatacept and belatacept inhibit CD28-mediated T cell activation by binding CD80 (B7-1) and CD86 (B7-2) costimulatory ligands and are clinically proven immunosuppressants used for rheumatoid arthritis and renal transplantation, respectively. Abatacept and belatacept preferentially bind CD80, yet CD86 has been implicated as the dominant ligand for CD28-mediated costimulation of T cells. We investigated the immunosuppressive effects of ASP2408, a novel CTLA4-Ig with CD86 selectivity and high potency created by directed evolution methods...
September 19, 2016: International Immunopharmacology
Tara M Strutt, Karl Kai McKinstry, Yi Kuang, Caroline M Finn, Ji Hae Hwang, Kunal Dhume, Stewart Sell, Susan L Swain
Memory T cells can often respond against pathogens that have evaded neutralizing Abs and are thus key to vaccine-induced protection, yet the signals needed to optimize their responses are unclear. In this study, we identify a dramatic and selective requirement for IL-6 to achieve optimal memory CD4 T cell recall following heterosubtypic influenza A virus (IAV) challenge of mice primed previously with wild-type or attenuated IAV strains. Through analysis of endogenous T cell responses and adoptive transfer of IAV-specific memory T cell populations, we find that without IL-6, CD4(+), but not CD8(+), secondary effector populations expand less and have blunted function and antiviral impact...
September 19, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Christopher S Eickhoff, Xiuli Zhang, Jose R Vasconcelos, R Geoffrey Motz, Nicole L Sullivan, Kelly O'Shea, Nicola Pozzi, David W Gohara, Jennifer R Blase, Enrico Di Cera, Daniel F Hoft
Trypanosoma cruzi infection is controlled but not eliminated by host immunity. The T. cruzi trans-sialidase (TS) gene superfamily encodes immunodominant protective antigens, but expression of altered peptide ligands by different TS genes has been hypothesized to promote immunoevasion. We molecularly defined TS epitopes to determine their importance for protection versus parasite persistence. Peptide-pulsed dendritic cell vaccination experiments demonstrated that one pair of immunodominant CD4+ and CD8+ TS peptides alone can induce protective immunity (100% survival post-lethal parasite challenge)...
September 2016: PLoS Pathogens
Lijun Meng, Shaoyan Hu, Jian Wang, Shan He, Yi Zhang
Dendritic cells (DCs) are critical regulators of adaptive immune responses. DCs can elicit primary T cell responses at low DC:T cell ratios through their expression of high levels of antigen-presenting molecules and costimulatory molecules. DCs are important for induction of functionally diverse T cell subsets such as CD4(+) T helper (Th)1 and Th17 cells and effector CD8(+) T cells able to reside in epithelial tissues. Recent studies begin illuminating the underlying mechanism by which DCs regulate specialized T cell subsets...
September 14, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Hu Zeng, Sivan Cohen, Cliff Guy, Sharad Shrestha, Geoffrey Neale, Scott A Brown, Caryn Cloer, Rigel J Kishton, Xia Gao, Ben Youngblood, Mytrang Do, Ming O Li, Jason W Locasale, Jeffrey C Rathmell, Hongbo Chi
Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses...
September 20, 2016: Immunity
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"