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T cell immunity

Mohammad Islamuddin, Garima Chouhan, Muzamil Yaqub Want, Hani A Ozbak, Hassan A Hemeg, Farhat Afrin
BACKGROUND: The therapy of visceral leishmaniasis (VL) is limited by resistance, toxicity and decreased bioavailability of the existing drugs coupled with dramatic increase in HIV-co-infection, non-availability of vaccines and down regulation of cell-mediated immunity (CMI). Thus, we envisaged combating the problem with plant-derived antileishmanial drug that could concomitantly mitigate the immune suppression of the infected hosts. Several plant-derived compounds have been found to exert leishmanicidal activity via immunomodulation...
October 2016: PLoS Neglected Tropical Diseases
Guanhua Song, Bingyu Liu, Zhihui Li, Haifeng Wu, Peng Wang, Kai Zhao, Guosheng Jiang, Lei Zhang, Chengjiang Gao
TBK1 is essential for interferon-β (IFN-β) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation. RNF128 directly interacted with TBK1 through its protease-associated (PA) domain and catalyzed the K63-linked polyubiquitination of TBK1, which led to TBK1 activation, IRF3 activation and IFN-β production. Deficiency of RNF128 expression attenuated IRF3 activation, IFN-β production and innate antiviral immune responses to RNA and DNA viruses, in vitro and in vivo...
October 24, 2016: Nature Immunology
Bing Kan, Li Yang, Yan-Jun Wen, Jin-Rong Yang, Ting Niu, Jiong Li, Hong-Xin Deng, Wei Wei, Li-Gong Chen, Quan Zhang, Wei Wang, Yu-Quan Wei
Vascular endothelial growth factor (VEGF) is an important regulating molecule of angiogenesis in tumor formation and progression. Cancer cells always secrete VEGF to stimulate angiogenesis that facilitate growth and invasion of the tumor. In this study, we established a VEGF164 overexpressing LL/2 lung cancer cell model and found that the postirradiated VEGF164-modified tumor cells protected the host against the challenge with LL/2 wild-type tumor cells. Histochemical assay showed that there were large areas of tumor necrosis with macrophage infiltration in the mice vaccinated with the VEGF164-modified tumor vaccine...
October 21, 2016: Anti-cancer Drugs
Jennie Johnstone, Robin Parsons, Fernando Botelho, Jamie Millar, Shelly McNeil, Tamas Fulop, Janet E McElhaney, Melissa K Andrew, Stephen D Walter, P J Devereaux, Mehrnoush Malek, Ryan R Brinkman, Jonathan Bramson, Mark Loeb
OBJECTIVES: To determine whether immune phenotypes associated with immunosenescence are predictive of frailty and mortality within 1-year in elderly nursing home residents. DESIGN: Cross sectional study of frailty; prospective cohort study of mortality. SETTING: Thirty-two nursing homes in four Canadian cities between September 2009 and October 2011. PARTICIPANTS: Nursing home residents aged 65 and older (N = 1,072, median age 86, 72% female)...
October 24, 2016: Journal of the American Geriatrics Society
Kelly D Moynihan, Cary F Opel, Gregory L Szeto, Alice Tzeng, Eric F Zhu, Jesse M Engreitz, Robert T Williams, Kavya Rakhra, Michael H Zhang, Adrienne M Rothschilds, Sudha Kumari, Ryan L Kelly, Byron H Kwan, Wuhbet Abraham, Kevin Hu, Naveen K Mehta, Monique J Kauke, Heikyung Suh, Jennifer R Cochran, Douglas A Lauffenburger, K Dane Wittrup, Darrell J Irvine
Checkpoint blockade with antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor regression in metastatic cancer, but these dramatic responses are confined to a minority of patients. This suboptimal outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint. Here we describe a combination immunotherapy that recruits a variety of innate and adaptive immune cells to eliminate large tumor burdens in syngeneic tumor models and a genetically engineered mouse model of melanoma; to our knowledge tumors of this size have not previously been curable by treatments relying on endogenous immunity...
October 24, 2016: Nature Medicine
Vera L Tunitskaya, Olesja V Eliseeva, Vladimir T Valuev-Elliston, Daria A Tyurina, Natalia F Zakirova, Olga A Khomich, Martins Kalis, Oleg E Latyshev, Elizaveta S Starodubova, Olga N Ivanova, Sergey N Kochetkov, Maria G Isaguliants, Alexander V Ivanov
Hepatitis delta virus (HDV) is a viroid-like blood-borne human pathogen that accompanies hepatitis B virus infection in 5% patients. HDV has been studied for four decades; however, the knowledge on its life-cycle and pathogenesis is still sparse. The studies are hampered by the absence of the commercially-available HDV-specific antibodies. Here, we describe a set of reproducible methods for the expression in E. coli of His-tagged small antigen of HDV (S-HDAg), its purification, and production of polyclonal anti-S-HDAg antibodies in rabbits...
October 20, 2016: International Journal of Molecular Sciences
Bethany L Mundy-Bosse, Steven D Scoville, Li Chen, Kathleen McConnell, Hsiaoyin C Mao, Elshafa H Ahmed, Nicholas Zorko, Sophia Harvey, Jordan Cole, Xiaoli Zhang, Stefan Costinean, Carlo M Croce, Karilyn Larkin, John C Byrd, Sumithira Vasu, William Blum, Jianhua Yu, Aharon G Freud, Michael A Caligiuri
Natural killer (NK) cells can have potent antileukemic activity following haplo-mismatched, T cell-depleted stem cell transplantations for the treatment of acute myeloid leukemia (AML), but they are not successful in eradicating de novo AML. Here, we have used a mouse model of de novo AML to elucidate the mechanisms by which AML evades NK cell surveillance. NK cells in leukemic mice displayed a marked reduction in the cytolytic granules perforin and granzyme B. Further, as AML progressed, we noted the selective loss of an immature subset of NK cells in leukemic mice and in AML patients...
October 24, 2016: Journal of Clinical Investigation
Hanna Starobinets, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, Jayanta Debnath
The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy...
October 24, 2016: Journal of Clinical Investigation
Antigona Ulndreaj, Apostolia Tzekou, Andrea J Mothe, Ahad Siddiqui, Rachel Dragas, Charles Tator, Emina Torlakovic, Michael Fehlings
The immune system plays a critical and complex role in the pathobiology of spinal cord injury (SCI), exerting both beneficial and detrimental effects. Increasing evidence suggests that there are injury level-dependent differences in the immune response to SCI. Patients with traumatic SCI have elevated levels of circulating autoantibodies against components of the central nervous system (CNS), but the role of these antibodies in SCI outcomes remains unknown. In rodent models of mid-thoracic SCI, antibody-mediated autoimmunity appears to be detrimental to recovery...
October 24, 2016: Journal of Neurotrauma
Cameron Browne
This paper concerns modeling the coupled within-host population dynamics of virus and CTL (Cytotoxic T Lymphocyte) immune response. There is substantial evidence that the CTL immune response plays a crucial role in controlling HIV in infected patients. Recent experimental studies have demonstrated that certain CTL variants can recognize HIV infected cells early in the infected cell lifecycle before viral production, while other CTLs only detect viral proteins (epitopes) presented on the surface of infected cells after viral production...
October 1, 2016: Mathematical Biosciences and Engineering: MBE
Jia Sun, Jintang Sun, Bingfeng Song, Lin Zhang, Qianqian Shao, Yanguo Liu, Daoying Yuan, Yun Zhang, Xun Qu
In tumor microenvironment, macrophages as a polarized M2 population promote tumor progression via releasing multiple cytokines and chemokines. A brown seaweed fucose-rich polysaccharide, fucoidan has antitumor activity and immune modulation through affecting tumor cells and lymphocytes. Here, we focused on the effect of fucoidan on macrophages especially M2 subtype. Our results demonstrated that fucoidan down-regulated partial cytokines and chemokines, especially a M2-type chemokine CCL22. Furthermore, fucoidan inhibited tumor cells migration and CD4(+) T lymphocytes, especially Treg cells, recruitment induced by M2 macrophages conditioned medium through suppression of CCL22...
October 24, 2016: Scientific Reports
Meriem Attaf, Stephan J Holland, Istvan Bartok, Julian Dyson
αβ T cells respond to peptide epitopes presented by major histocompatibility complex (MHC) molecules. The role of T cell receptor (TCR) germline complementarity determining regions (CDR1 and 2) in MHC restriction is not well understood. Here, we examine T cell development, MHC restriction and antigen recognition where germline CDR loop structure has been modified by multiple glycine/alanine substitutions. Surprisingly, loss of germline structure increases TCR engagement with MHC ligands leading to excessive loss of immature thymocytes...
October 24, 2016: Scientific Reports
Lulu Jiang, Charles C T Hindmarch, Mark Rogers, Colin Campbell, Christy Waterfall, Jane Coghill, Peter W Mathieson, Gavin I Welsh
Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or 'podocytes', the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells...
October 24, 2016: Scientific Reports
Dana Tedesco, Manoj Thapa, Sanjeev Gumber, Elizabeth J Elrod, Khalidur Rahman, Chris C Ibegbu, Joseph F Magliocca, Andrew B Adams, Frank Anania, Arash Grakoui
: Persistent hepatotropic viral infections are a common etiologic agent of chronic liver disease. Unresolved infection can be attributed to non-functional intrahepatic CD8+ T cell responses. In light of dampened CD8+ T cell responses, liver disease often manifests systemically as Ig-related syndromes due to aberrant B cell functions. These two opposing yet co-existing phenomena implicate the potential of altered CD4+ T cell help. Elevated CD4+ Foxp3+ T cells were evident in both human liver disease and a mouse model of chemically induced liver injury despite marked activation and spontaneous IgG production by intrahepatic B cells...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Mazen Al-Hommrani, Paramita Chakraborty, Shilpak Chatterjee, Shikhar Mehrotra
Cell, the basic unit of life depends for its survival on nutrients and thereby energy to perform its physiological function. Cells of lymphoid and myeloid origin are key in evoking an immune response against "self" or "non-self" antigens. The thymus derived lymphoid cells called T cells are a heterogenous group with distinct phenotypic and molecular signatures that have been shown to respond against an infection (bacterial, viral, protozoan) or cancer. Recent studies have unearthed the key differences in energy metabolism between the various T cell subsets, natural killer cells, dendritic cells, macrophages and myeloid derived suppressor cells...
2016: J Immunol Res Ther
Sandra Demaria, C Norman Coleman, Silvia C Formenti
Immune checkpoint inhibitors are effective in cancer treatment. A pre-existing immune response demonstrated by significant pretreatment tumor lymphocytic infiltration is a pre-requisite for response. Within such infiltrated tumors, referred as "hot", immune checkpoint inhibitors rescue anti-tumor T cells activity. In contrast, "cold" tumors lack lymphocytic infiltration and are refractory to immunotherapy. Preclinical data show that radiotherapy sensitizes refractory tumors to immune checkpoint inhibitors by recruiting anti-tumor T cells...
June 2016: Trends in Cancer
Ying Wang, Lili Wang, Haoyu Yang, Weichang Yuan, Jingyi Ren, Yanping Bai
Circulating T follicular helper (cTfh) cells are known to be involved in numerous immune-mediated diseases, but their pathological role in psoriasis is less fully investigated. Herein, we aimed to identify whether cTfh cells contributed to the pathogenesis of psoriasis. The frequency and function of cTfh cells were compared between patients with psoriasis vulgaris and healthy controls, and the infiltration of Tfh cells was detected between lesional and nonlesional skin tissues of psoriasis patients. Moreover, the dynamic change of cTfh cells before and after acitretin treatment was evaluated...
2016: Journal of Immunology Research
Lize Cuypers, Guangdi Li, Christoph Neumann-Haefelin, Supinya Piampongsant, Pieter Libin, Kristel Van Laethem, Anne-Mieke Vandamme, Kristof Theys
Despite significant progress in hepatitis C (HCV) treatment, global viral eradication remains a challenge. An in-depth map of its genome diversity within the context of structural and immunological constraints could contribute to the design of pan-genotypic antivirals and preventive vaccines. For such analyses, extensive information is only available for the highly prevalent HCV genotypes (GT) 1a and 1b. Using 647 GT1a and 408 GT1b full-genome sequences obtained from the Los Alamos database, we found that respectively 3 per cent and 82 per cent of all codon positions are under positive and negative selective pressure, suggesting variation mainly accumulates due to random genetic drift...
July 2016: Virus Evolution
Silvia Pesce, Lorenzo Moretta, Alessandro Moretta, Emanuela Marcenaro
Innate and adaptive immunity has evolved complex molecular mechanisms regulating immune cell migration to facilitate the dynamic cellular interactions required for its function involving the chemokines and their receptors. One important chemokine receptor in the immune system is represented by CCR7. Together with its ligands CCL19 and CCL21, this chemokine receptor controls different arrays of migratory events, both in innate and adaptive immunity, including homing of CD56(bright) NK cells, T cells, and DCs to lymphoid compartments, where T cell priming occurs...
2016: Frontiers in Immunology
Adriaan A van Beek, Bruno Sovran, Floor Hugenholtz, Ben Meijer, Joanne A Hoogerland, Violeta Mihailova, Corine van der Ploeg, Clara Belzer, Mark V Boekschoten, Jan H J Hoeijmakers, Wilbert P Vermeij, Paul de Vos, Jerry M Wells, Pieter J M Leenen, Claudio Nicoletti, Rudi W Hendriks, Huub F J Savelkoul
Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-week bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1(-/Δ7) mice, which have a median lifespan of ~20 weeks, and their wild-type littermates. The colonic barrier in Ercc1(-/Δ7) mice was characterized by a thin (< 10 μm) mucus layer...
2016: Frontiers in Immunology
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