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Scott N Furlan, Benjamin Watkins, Victor Tkachev, Sarah Cooley, Angela Panoskaltsis-Mortari, Kayla Betz, Melanie Brown, Daniel J Hunt, John B Schell, Katie Zeleski, Alison Yu, Cindy Giver, Edmund Waller, Jeffrey S Miller, Bruce R Blazar, Leslie S Kean
One of the central challenges of transplantation is the development of alloreactivity despite the use of multi-agent immunoprophylaxis. Effective control of this immune-suppression-resistant T cell activation represents one of the key unmet needs in the fields of both solid organ and hematopoietic stem cell transplant (HCT). To address this unmet need, we have used a highly-translational non-human primate model to interrogate the transcriptional signature of T cells during Breakthrough Acute GVHD that occurs in the setting of clinically-relevant immune suppression and compared this to the Hyperacute GVHD, that develops in unprophylaxed or sub-optimally prophylaxed transplant recipients...
October 6, 2016: Blood
Marie de Bourayne, Yann Gallais, Zeina El Ali, Philippe Rousseau, Marie-Hélène Damiens, Claude Cochet, Odile Filhol, Sylvie Chollet-Martin, Marc Pallardy, Saadia Kerdine-Römer
Allergic contact dermatitis (ACD) represents a severe health problem with increasing worldwide prevalence. It is a T-cell-mediated inflammatory skin disease caused by chemicals present in the daily or professional environment. NiSO4 and 2,4-dinitrochlorobenzene (DNCB) are 2 chemicals involved in ACD. These contact sensitizers are known to induce an up-regulation of phenotypic markers and cytokine secretion in dendritic cells (DCs; professional APCs), leading to the generation of CD8(+) Tc1/Tc17 and CD4(+) Th1/Th17 effector T cells...
October 5, 2016: Journal of Leukocyte Biology
Yalei Liu, Ran You, Nan Yu, Yan Gong, Chenxue Qu, Yang Zhang, Guizhi Lu, Youyuan Huang, Hong Zhang, Ying Gao, Yanming Gao, Xiaohui Guo
Both cellular and humoral responses play important roles in the pathogenesis of Hashimoto's thyroiditis (HT). However, the immunological differences between euthyroid (mild HT) and hypothyroid (severe HT) patients are unknown. This study aimed to investigate the distribution of lymphocyte subsets and cytokine profiles in HT patients with differences in thyroid function. Peripheral blood was drawn from 18 healthy controls and 54 HT patients (33 patients with mild HT, 21 patients with severe HT). The percentages of B cell subsets, T cell subsets and NK cells were analyzed by flow cytometry...
September 23, 2016: International Immunopharmacology
Long Chen, Gang Chen, Ming-Qiang Zhang, Xian-Zhi Xiong, Hong-Ju Liu, Jian-Bao Xin, Jian-Chu Zhang, Jiang-Hua Wu, Zhao-Ji Meng, Sheng-Wen Sun
Background. CD8(+) T lymphocytes are known to play a critical role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, systematic analyses of CD8(+) T cell (Cytotoxic T cells, Tc) subsets in COPD patients have yet to be well conducted. Methods. The whole Tc subsets, including Tc1/2/10/17, CD8(+) regulatory T cells (Tregs) and CD8(+) α7(+) T cells, were quantified by flow cytometry in peripheral blood from 24 stable COPD subjects (SCOPD), 14 patients during acute exacerbations (AECOPD), and 14 healthy nonsmokers (HN)...
2016: PeerJ
Zahra Salehi, Rozita Doosti, Masoumeh Beheshti, Ehsan Janzamin, Mohammad Ali Sahraian, Maryam Izad
Recent evidence points to a pathogenic role for CD8+ cytotoxic T (Tc) cells in Multiple sclerosis (MS). Based on cytokine profile, Tc cells can be divided into different subsets: IFN-γ (Tc1), IL-4 (Tc2), IL-10 (Tc10), IL-17 (Tc17), IL-21 (Tc21), IL-22 (Tc22) and TNF-α producing cells. In this study we evaluated the frequency of Tc cell subsets and the serum level of Tc17 differentiation cytokines in MS patients with different clinical patterns. We analyzed Tc cell subsets percentage in peripheral blood of relapsing-remitting (RRMS) (n = 28), secondary-progressive (SPMS) (n = 10) and primary-progressive (PPMS) (n = 4) MS patients in comparison to healthy controls (n = 15) using flow cytometry...
2016: PloS One
Michael R Tom, Ji Li, Aito Ueno, Miriam Fort Gasia, Ronald Chan, Daniel Y Hung, Shem Chenoo, Marietta Iacucci, Humberto B Jijon, Gilaad G Kaplan, Paul L Beck, Remo Panaccione, Herman W Barkema, Andre G Buret, Vijay Yajnik, Subrata Ghosh
BACKGROUND: Distinct CD8+ T-cell subsets such as interleukin-17-expressing Tc17 and Foxp3-expressing Tcreg are functionally similar to CD4+ T cells. Though CD4+ T cells are dysregulated in patients with inflammatory bowel disease (IBD), CD8+ T cells are not well investigated. Vitamin D is an environmental factor which influences T-cell subsets. We assessed the prevalence of CD8+ T-cell subsets among peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) of patients with Crohn's disease, patients with ulcerative colitis, and healthy controls...
July 2016: Inflammatory Bowel Diseases
Zhang Bao, Guohua Lu, Dawei Cui, Yinan Yao, Guangdie Yang, Jianying Zhou
Accumulating evidence has shown that T cells are crucial in shaping the tumor microenvironment and regulating tumor development. However, the roles of IL-17A‑producing T cells (IL-17A+CD4+ Th17, IL-17A+CD8+ Tc17 and IL-17A+ γδT17 cells) and related cytokines in the progression of lung cancer (LC) remain uncertain. Here, we found that the frequencies of both Th17 and γδT17 cells in the peripheral blood of patients with lung adenocarcinoma (LA) were higher than those in healthy controls (HCs), whereas the frequency of Tc17 cells in the patients with LA was decreased...
August 2016: Oncology Reports
Maxime Samson, Kim Heang Ly, Benjamin Tournier, Nona Janikashvili, Malika Trad, Marion Ciudad, Alexandrine Gautheron, Hervé Devilliers, Valérie Quipourt, François Maurier, Nadine Meaux-Ruault, Nadine Magy-Bertrand, Patrick Manckoundia, Paul Ornetti, Jean-Francis Maillefert, Jean-François Besancenot, Christophe Ferrand, Laura Mesturoux, François Labrousse, Anne-Laure Fauchais, Philippe Saas, Laurent Martin, Sylvain Audia, Bernard Bonnotte
CD8(+) T cells participate in the pathogenesis of some vasculitides. However, little is known about their role in Giant Cell Arteritis (GCA). This study was conducted to investigate CD8(+) T cell involvement in the pathogenesis of GCA. Analyses were performed at diagnosis and after 3 months of glucocorticoid treatment in 34 GCA patients and 26 age-matched healthy volunteers. Percentages of CD8(+) T-cell subsets, spectratype analysis of the TCR Vβ families of CD8(+) T cells, levels of cytokines and chemokines and immunohistochemistry of temporal artery biopsies (TAB) were assessed...
August 2016: Journal of Autoimmunity
Corinna Steckner, Andreas Weber, Anne K Mausberg, Maximilian Heininger, Felicitas Opdenhövel, Bernd C Kieseier, Hans P Hartung, Harald H Hofstetter
Interleukin 17 (IL-17), produced by T cells, plays an important role in Multiple Sclerosis (MS) and its animal model, Experimental Autoimmune Encephalomyelitis (EAE). In contrast to IL-17-producing CD4+ T cells, the contribution of IL-17-producing CD8+ T cells (Tc17) in CNS autoimmunity has been investigated less intensively. Here we investigate the role of TC17 in EAE. We compare different T cell populations and their cytokine pattern in the MOG35-55- and MOG37-50-induced EAE. We detected a similar cytokine phenotype for both EAE models in the autoimmune process assessed at different stages...
September 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Olga Brandstätter, Oliver Schanz, Julia Vorac, Jessica König, Tetsushi Mori, Toru Maruyama, Markus Korkowski, Thomas Haarmann-Stemmann, Dorthe von Smolinski, Joachim L Schultze, Josef Abel, Charlotte Esser, Haruko Takeyama, Heike Weighardt, Irmgard Förster
As a sensor of polyaromatic chemicals the aryl hydrocarbon receptor (AhR) exerts an important role in immune regulation besides its requirement for xenobiotic metabolism. Transcriptional activation of AhR target genes is counterregulated by the AhR repressor (AhRR) but the exact function of the AhRR in vivo is currently unknown. We here show that the AhRR is predominantly expressed in immune cells of the skin and intestine, different from other AhR target genes. Whereas AhRR antagonizes the anti-inflammatory function of the AhR in the context of systemic endotoxin shock, AhR and AhRR act in concert to dampen intestinal inflammation...
2016: Scientific Reports
J Ma, L-L Shi, Y-K Deng, H Wang, P-P Cao, X-B Long, X-H Zhang, Y Liu, M Zeng, Z Liu
BACKGROUND: CD8(+) T cells are important effectors of cell-mediated immunity; however, their contribution to the pathogenesis of CRS is unclear. OBJECTIVE: This study aimed to characterize the cytokine-producing features and cytotoxic activity of CD8(+) T cells, and their correlation with inflammation patterns in CRS with nasal polyps. METHODS: The expression of IFN-γ, IL-4, IL-5, IL-17A, forkhead box P3 (FOXP3), perforin, and granzyme B in CD8(+) T cells was studied by means of flow cytometry, immunohistochemistry, and immunofluorescence...
September 2016: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Ushani Srenathan, Kathryn Steel, Leonie S Taams
The pro-inflammatory cytokine interleukin-17A (IL-17) has been the subject of research by many groups worldwide. IL-17 expression is often associated with a specific subset of CD4+ T cells (the so-called Th17 cells); however various other immune cell subsets can also synthesise and express IL-17, including CD8+ T cells. Here we review recent data regarding the presence of IL-17+ CD8+ T cells (also known as Tc17 cells) in human inflammatory disease, discuss current knowledge regarding the culture conditions required for the differentiation of these cells in humans and mice, and describe key phenotypic and functional features...
October 2016: Immunology Letters
Huilong Chen, Xiangqin Xu, Jieming Teng, Sheng Cheng, Hansvin Bunjhoo, Yong Cao, Jin Liu, Jungang Xie, Congyi Wang, Yongjian Xu, Weining Xiong
Accumulating evidence suggests that chemokine (C-X-C motif) ligand 12 (CXCL12) and its receptor chemokine (C-X-C motif) receptor 4 (CXCR4) may contribute to the pathogenesis of allergic asthma. However, the underlying molecular mechanisms remain to be fully understood. T-helper 17 cells (Th17) and T-cytotoxic 17 cells (Tc17) have been implicated in the development of several allergic disorders, including asthma. The present study aimed to explore the association between CXCL12 signaling and Th17/Tc17 cells in the development of asthma...
May 2016: Experimental and Therapeutic Medicine
Min-Chao Duan, Jian-Quan Zhang, Yue Liang, Guang-Nan Liu, Jin Xiao, Hai-Juan Tang, Yi Liang
Chronic obstructive pulmonary disease (COPD) is a progressive and irreversible chronic inflammatory disease associated with the accumulation of activated T cells. To date, there is little information concerning the intrinsic association among Th17, Tc17, and regulatory T (Treg) cells in COPD. The objective of this study was to investigate the variation of lungs CD4(+)Foxp3(+) Treg cells and IL-17-producing CD4 and CD8 (Th17 and Tc17) lymphocytes in mice with cigarette-induced emphysema. Groups of mice were exposed to cigarette smoke or room air...
August 2016: Inflammation
Hsin-Wei Chen, Jy-Ping Tsai, Tsung-You Yao, Chia-Ling Hsieh, I-Hua Chen, Shin-Jen Liu
TGF-β together with IL-21 or IL-6 can drive the differentiation of naïve CD8(+) T cells into IL-17-producing CD8(+) T cells. These IL-17-producing CD8(+) T cells are termed Tc17 cells. Tc17 cells preserve plasticity under various conditions in vitro and in vivo. IFN-γ-producing CD8(+) T cells are termed Tc1 cells. However, Tc1 cells are considered relatively stable. In the present study, we show that the combination of TGF-β plus IL-21, but not IL-6, converts Tc1 cells into Tc17 cells; this conversion is associated with elevated RORα, RORγt, and Batf mRNA levels...
June 2016: Immunology Letters
Wei-Han Xu, Xiao-Ling Hu, Xiao-Fang Liu, Peng Bai, Yong-Chang Sun
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by progressive loss of lung function and local and systemic inflammation, in which CD8+ T-cells are believed to play a key role. Activated CD8+ T-cells differentiate into distinct subpopulations, including interferon-γ (IFN-γ)-producing Tc1 and interleukin (IL)-17-producing Tc17 cells. Recent evidence indicates that Tc17 cells exhibit considerable plasticity and may convert into IL-17/IFN-γ-double producing (Tc17/IFN-γ) cells when driven by inflammatory conditions...
April 20, 2016: Chinese Medical Journal
Rushikesh Sudam Patil, Sagar Umesh Shah, Shailesh Vinayak Shrikhande, Mahesh Goel, Rajesh Prabhakar Dikshit, Shubhada Vivek Chiplunkar
Despite conventional treatment modalities, gallbladder cancer (GBC) remains a highly lethal malignancy. Prognostic biomarkers and effective adjuvant immunotherapy for GBC are not available. In the recent past, immunotherapeutic approaches targeting tumor associated inflammation have gained importance but the mediators of inflammatory circuit remain unexplored in GBC patients. In the current prospective study, we investigated the role of IL17 producing TCRγδ(+) (Tγδ17), CD4(+) (Th17), CD8(+) (Tc17) and regulatory T cells (Tregs) in pathogenesis of GBC...
August 15, 2016: International Journal of Cancer. Journal International du Cancer
Min Zhang, Guang-Min Nong, Min Jiang, Wen-Jie Zhan
OBJECTIVE: To determine the proportion of Tc17 cells in the lungs of mice with neutrophilic(NEU) asthma, and to investigate the role of Tc17 cells in the pathogenesis of NEU asthma. METHODS: Thirty-two C57/B6 mice of clean grade were randomly divided into two groups: NEU asthma and control. The mice in the NEU asthma group were sensitized by airway instillation of ovalbumin (OVA) and lipopolysaccharide (LPS), and challenged with an aerosol of OVA, while those in the control group were sensitized and challenged with normal saline...
February 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Paola Lovato, Hanne Norsgaard, Yoshiki Tokura, Mads A Røpke
BACKGROUND: Psoriasis vulgaris is characterised by epidermal hyper-proliferation and infiltration of immune cells including dendritic cells (DCs) and T cells. The inflammation is driven by a complex interplay between immune and skin cells involving interleukin (IL)-17A, IL-23 and TNF-α as key drivers. The calcipotriol/betamethasone dipropionate two-compound fixed combination product is widely used for topical treatment of psoriasis. However, the mechanism behind its high efficacy has not been elucidated in detail...
March 2016: Journal of Dermatological Science
Mi Ra Chang, Venkatasubramanian Dharmarajan, Christelle Doebelin, Ruben D Garcia-Ordonez, Scott J Novick, Dana S Kuruvilla, Theodore M Kamenecka, Patrick R Griffin
The T cell specific RORγ isoform RORγt has been shown to be the key lineage-defining transcription factor to initiate the differentiation program of TH17 and TC17 cells, cells that have demonstrated antitumor efficacy. RORγt controls gene networks that enhance immunity including increased IL17 production and decreased immune suppression. Both synthetic and putative endogenous agonists of RORγt have been shown to increase the basal activity of RORγt enhancing TH17 cell proliferation. Here, we show that activation of RORγt using synthetic agonists drives proliferation of TH17 cells while decreasing levels of the immune checkpoint protein PD-1, a mechanism that should enhance antitumor immunity while blunting tumor associated adaptive immune resistance...
April 15, 2016: ACS Chemical Biology
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