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Regulatory T lymphocyte

Vivek Murthy, Janna Minehart, Daniel H Sterman
Modern cancer immunotherapies represent a major shift in paradigm with respect to how we understand innate and adaptive responses to malignancy. Successful tumors co-opt normal immunosurveillance mechanisms by potent interactions between the tumor and local draining lymph nodes. Tumor cells mediate a complex and dynamic immunoediting procedure that results in increased vascular efflux into the draining lymphatics, an immunosuppressive microenvironment rich in regulatory T-lymphocytes, dysfunctional antigen presentation, and downregulation of normal effector lymphocyte responses...
December 1, 2017: Journal of the National Cancer Institute
Peijuan Wang, Yan Lu, Si Chen, Yue Chen, Chunping Hu, Yawei Zuo
Autoimmune abnormality is one of the main causes of premature ovarian failure (POF). Bu Shen Huo Xue formula (BSHXF), a traditional Chinese medicine formula, has been clinically used for the treatment of patients with POF in China. Regulatory T cells (Tregs) are important in the pathogenesis of autoimmune POF. The aim of the present study was to evaluate the immunoprotective effects of BSHXF on POF and the underlying mechanisms. An experimental autoimmune POF model was induced in B6AF1 mice with zona pellucida 3 (ZP3) fragments...
April 2018: Experimental and Therapeutic Medicine
Daniela Dukovska, Daniel Fernández-Soto, Mar Valés-Gómez, Hugh T Reyburn
The biology and function of NKG2H receptor, unlike the better characterized members of the NKG2 family NKG2A, NKG2C, and NKG2D, remains largely unclear. Here, we show that NKG2H is able to associate with the signaling adapter molecules DAP12 and DAP10 suggesting that this receptor can signal for cell activation. Using a recently described NKG2H-specific monoclonal antibody (mAb), we have characterized the expression and function of lymphocytes that express this receptor. NKG2H is expressed at the cell surface of a small percentage of peripheral blood mononuclear cell (PBMC) and is found more frequently on T cells, rather than NK cells...
2018: Frontiers in Immunology
Zhaodong Li, Ludovica F Buttó, Kristine-Anne Buela, Li-Guo Jia, Minh Lam, John D Ward, Theresa T Pizarro, Fabio Cominelli
Death receptor 3 (DR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, has been implicated in regulating T-helper type-1 (TH 1), type-2 (TH 2), and type-17 (TH 17) responses as well as regulatory T cell (Treg ) and innate lymphoid cell (ILC) functions during immune-mediated diseases. However, the role of DR3 in controlling lymphocyte functions in inflammatory bowel disease (IBD) is not fully understood. Recent studies have shown that activation of DR3 signaling modulates Treg expansion suggesting that stimulation of DR3 represents a potential therapeutic target in human inflammatory diseases, including Crohn's disease (CD)...
2018: Frontiers in Immunology
Lorenza Tulli, Francesca Cattaneo, Juliette Vinot, Cosima T Baldari, Ugo D'Oro
Toll-like receptors (TLRs) play a key role in the activation of innate immune cells, in which their engagement leads to production of cytokines and co-stimulatory molecules. TLRs signaling requires recruitment of toll/IL-1R (TIR) domain-containing adaptors, such as MyD88 and/or TRIF, and leads to activation of several transcription factors, such as NF-κB, the AP1 complex, and various members of the interferon regulatory factor (IRF) family, which in turn results in triggering of several cellular functions associated with these receptors...
2018: Frontiers in Immunology
Bin Zhao, Jun-Jie Xia, Lu-Min Wang, Chang Gao, Jia-Li Li, Jia-Yin Liu, Qi-Jun Cheng, Chen Dai, Qi-Lin Ma, Zhong-Quan Qi, Ben-Hua Zhao
The role of arsenic trioxide (As2 O3 ) in inhibiting immune rejection and prolonging islet allograft survival has been identified in islet allotransplantation. This study aims to explore the role of As2 O3 in islet xenotransplantation and the action mechanism. The streptozotocin (STZ) was used in C57BL/6 mice to induce the type 1 diabetes mellitus (T1DM) for xenotransplantation models establishment. Donor islets were isolated by digesting. The flow cytometry (FCM) was used to analyze lymphocyte types. The blood sugar level was detected by using intraperitoneal glucose tolerance test (IPGTT)...
March 14, 2018: Cell Death & Disease
Mathew A Cherian, Sydney Olson, Hemalatha Sundaramoorthi, Kitra Cates, Xiaogang Cheng, John Harding, Andrew Martens, Grant A Challen, Manoj Tyagi, Lee Ratner, Daniel Rauch
The human T cell leukemia virus-1 (HTLV-1) oncoprotein Tax drives cell proliferation and resistance to apoptosis early in the pathogenesis of adult T-cell leukemia (ATL). Subsequently, likely as a result of specific immuno-editing, Tax expression is downregulated and functionally replaced by somatic driver mutations of the host genome. Both amplification and point mutations of interferon regulatory factor 4 (IRF4) have been previously detected in ATL, and the K59R mutation is the most common single-nucleotide variation in IRF4 and is found exclusively in ATL...
March 14, 2018: Journal of Biological Chemistry
Denise C Hsu, Kimberly F Breglio, Luxin Pei, Chun-Shu Wong, Bruno B Andrade, Virginia Sheikh, Margery Smelkinson, Constantinos Petrovas, Adam Rupert, Leonardo Gil-Santana, Adrian Zelazny, Steven M Holland, Kenneth Olivier, Daniel Barber, Irini Sereti
Background: Immune reconstitution inflammatory syndrome (IRIS) is an aberrant inflammatory response in individuals with advanced human immunodeficiency virus (HIV) infection, after antiretroviral therapy (ART) initiation. The pathogenesis of Mycobacterium avium complex (MAC)-associated IRIS has not been fully elucidated. Methods: We investigated monocyte and CD4+ T-cell responses in vitro, tumor necrosis factor (TNF) expression in tissues, and plasma cytokines and inflammatory markers, in 13 HIV-infected patients with MAC-IRIS and 14 HIV-uninfected patients with pulmonary MAC infection...
March 10, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Tomohisa Okamura, Kazuhiko Yamamoto, Keishi Fujio
Regulatory T cells (Tregs) are necessary for the maintenance of immune tolerance. Tregs are divided into two major populations: one is thymus derived and the other develops in the periphery. Among these Tregs, CD4+ CD25+ Tregs, which mainly originate in the thymus, have been extensively studied. Transcription factor Foxp3 is well known as a master regulatory gene for the development and function of CD4+ CD25+ Tregs. On the other hand, peripheral Tregs consist of distinct cell subsets including Foxp3-dependent extrathymically developed Tregs and interleukin (IL)-10-producing type I regulatory T (Tr1) cells...
2018: Frontiers in Immunology
Taku Kuwabara, Yukihide Matsui, Fumio Ishikawa, Motonari Kondo
The adaptive immune system involves antigen-specific host defense mechanisms mediated by T and B cells. In particular, CD4⁺ T cells play a central role in the elimination of pathogens. Immunological tolerance in the thymus regulates T lymphocytes to avoid self-components, including induction of cell death in immature T cells expressing the self-reactive T-cell receptor repertoire. In the periphery, mature T cells are also regulated by tolerance, e.g., via induction of anergy or regulatory T cells. Thus, T cells strictly control intrinsic signal transduction to prevent excessive responses or self-reactions...
March 12, 2018: International Journal of Molecular Sciences
Brittany P Lassiter, Siqi Guo, Stephen J Beebe
Nano-pulse stimulation (NPS), previously called nsPEFs, induced a vaccine-like effect after ablation of orthotopic N1-S1 hepatocellular carcinoma (HCC), protecting rats from subsequent challenges with N1-S1 cells. To determine immunity, immune cell phenotypes were analyzed in naïve, treated and protected rats. NPS provides a positive, post-ablation immuno-therapeutic outcome by alleviating immunosuppressive T regulatory cells (Treg) in the tumor microenvironment (TME), allowing dendritic cell influx and inducing dynamic changes in natural killer cells (NKs), NKT-cells and T-lymphocytes in blood, spleen and liver...
March 13, 2018: Cancers
Angela Deyà-Martínez, Ana Esteve-Solé, Natalia Vélez-Tirado, Veronica Celis, Jordi Costa, Maria Cols, Cristina Jou, Alexandru Vlagea, Ana María Plaza-Martin, Manel Juan, Laia Alsina
BACKGROUND: One of the most frequent non-infectious complications of humoral immunodeficiencies with a CVID-like pattern is a particular form of inflammatory lung disease which is called granulomatous-lymphocytic interstitial lung disease (GLILD). Its development worsens patient prognosis, with a significant decrease in survival. Currently there are no unified guidelines regarding its management, and different combinations of immunosuppressants have been used with variable success. METHODS: Clinical and radiological data were collected from patient's medical charts...
March 12, 2018: Pediatric Allergy and Immunology
Asif Elahi, Subrata Sabui, Nell N Narasappa, Sudhanshu Agrawal, Nils W Lambrecht, Anshu Agrawal, Hamid M Said
Biotin (vitamin B7) is essential for human health because of its involvement, as a cofactor, in a variety of critical cellular metabolic reactions. Previous studies have shown that biotin deficiency enhances inflammation, and certain chronic inflammatory diseases are associated with biotin deficiency; however, the mechanisms that mediate the association between biotin status and inflammation are not well understood. In this study, we examined the effect of biotin deficiency on human CD4+ T cell responses to determine their role in biotin deficiency-associated inflammation...
March 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Michelle L Ratay, Stephen C Balmert, Ethan J Bassin, Steven R Little
Dry eye disease (DED), also known as keratoconjunctivitis sicca, is an ocular surface disease characterized by T-cell-mediated inflammation. Current therapeutics, such as immunosuppressive agents, act to suppress the clinical signs and inflammation. However, long-term usage of these treatments can cause severe side effects. In this study, we present an alternative therapeutic approach that utilizes a histone deacetylase inhibitor (HDACi) to regulate transcription of a variety of immunomodulatory genes. Specifically, HDACi have emerged as a potential anti-inflammatory agent, which can modulate the functions of a subset of suppressive T lymphocytes known as regulatory T cells (Tregs), enhancing FoxP3 acetylation and subsequently guarding the transcription factor from proteasomal degradation...
March 8, 2018: Acta Biomaterialia
Luka Brcic, Stefanie Stanzer, Dagmar Krenbek, Ulrike Gruber-Moesenbacher, Gudrun Absenger, Franz Quehenberger, Arschang Valipour, Joerg Lindenmann, Herbert Stoeger, Mohamed Al Effah, Melanie Fediuk, Marija Balic, Helmut H Popper
Squamous cell and adenocarcinomas of the lung develop different mechanisms during carcinogenesis to evade attacks of the immune system. Besides the well-known check-point control programmed death 1 and its ligand, many more mechanisms, acting either tumoricidal or in favor of tumor progression, exist. Analysis of the immune cell profiles in resected tissues and bronchoalveolar lavage samples and correlation between them and with overall survival data was performed. In all tumor samples in this study, cells of the immune system expressed a tumor-cooperating phenotype...
March 8, 2018: Virchows Archiv: An International Journal of Pathology
Mohamed B Ezzelarab, Lien Lu, William F Shufesky, Adrian E Morelli, Angus W Thomson
Donor-derived regulatory dendritic cell (DCreg) infusion before transplantation, significantly prolongs renal allograft survival in non-human primates. This is associated with enhanced expression of the immunoregulatory molecules cytotoxic T-lymphocyte-associated antigen (Ag) 4 (CTLA4) and programmed cell death protein 1 (PD1) by host donor-reactive T cells. In rodents and humans, CD28 co-stimulatory pathway blockade with the fusion protein CTLA4:Ig (CTLA4Ig) is associated with reduced differentiation and development of regulatory T cells (Treg)...
2018: Frontiers in Immunology
Almudena García-Ortiz, Juan M Serrador
Nitric oxide (NO) is a key messenger in the pathogenesis of inflammation, linking innate and adaptive immunity. By targeting signaling molecules, NO from inducible NO synthase (iNOS) and endothelial (e)NOS affects T helper cell differentiation and the effector functions of T lymphocytes, and is a potential target for therapeutic manipulation. In this review we discuss the regulatory actions exerted by NO on T cell functions, focusing on S-nitrosylation as an important post-translational modification by which NO acts as a signaling molecule during T cell-mediated immunity...
March 5, 2018: Trends in Molecular Medicine
Teerawut Nedumpun, Chaitawat Sirisereewan, Chanoknun Thanmuan, Pong Techapongtada, Rinlapas Puntarotairung, Sarun Naraprasertkul, Roongroje Thanawongnuwech, Sanipa Suradhat
Regulatory T lymphocytes (Treg) residing within the tissues, are known to possess immunosuppressive properties which contribute to immunomodulation within the organs. PRRSV infection usually weakens lung defense mechanisms, leading to porcine respiratory disease complex (PRDC). Induction of circulatory Treg is one of the reported mechanisms involved in PRRSV-induced immunomodulation. However, whether PRRSV can induce tissue-infiltrating Treg in the lungs and lymph nodes is still unclear. To investigate the effect of PRRSV on induction of porcine Treg in the tissues, we isolated mononuclear cells from the lungs and tracheobronchial lymph nodes, and identified the existence of Treg by flow cytometry...
March 2018: Veterinary Microbiology
Joni Keto, Tanja Kaartinen, Urpu Salmenniemi, Johanna Castrén, Jukka Partanen, Arno Hänninen, Matti Korhonen, Kaarina Lähteenmäki, Maija Itälä-Remes, Johanna Nystedt
Mesenchymal stromal cells (MSCs) are used as salvage therapy to treat steroid-refractory acute graft-versus-host disease (aGvHD). We studied the immunological response to MSC treatment in 16 aGvHD patients by assessing lymphocyte profiles and three proposed aGvHD serum markers during the MSC treatment. Surprisingly, there were no obvious differences in the lymphocyte profiles between the responders and non-responders. The numbers of T, B, and NK cells were below the normal reference interval in all patients...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Yang Liu, Yin Yao, Zhi-Chao Wang, Qing Ning, Zheng Liu
Host immunity (innate and adaptive immunity) plays essential roles in the pathogenesis of inflammatory upper airway diseases including allergic rhinitis and chronic rhinosinusitis. Recently, the discovery of novel innate immune cells, particularly innate lymphoid cells, has renewed our view on the role of innate immunity in inflammatory upper airway diseases. Meanwhile, the identification of new subsets of T helper (Th) cells including Th22, Th9 and follicular Th cells, and regulatory B cells in the adaptive immunity has broadened our knowledge on the complex immune networks in inflammatory upper airway diseases...
March 7, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
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