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Li Ping, Zhen Yang, Qin Zhang, Wei Wang, Jiong Yang
OBJECTIVE: In allergic asthma, regulatory T cell (Treg) number and function are decreased. Antigen primed CD8(+) T cells play an indispensable role in the full development of airway inflammation and airway hyper-responsiveness (AHR) occurring in asthma. In this study, we investigated the relationship between subpopulations of CD8(+) T cells and CD39(+) Tregs. METHODS: Female C57BL/6 mice were used to develop the model of allergic asthma. Experimental mice were immunized with ovalbumin (OVA) by intra-peritoneal (i...
March 27, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
Aditya Arra, Holger Lingel, Benno Kuropka, Jonas Pick, Tina Schnoeder, Thomas Fischer, Christian Freund, Mandy Pierau, Monika C Brunner-Weinzierl
As the blockade of inhibitory surface-molecules such as CTLA-4 on T cells has led to recent advances in antitumor immune therapy, there is great interest in identifying novel mechanisms of action of CD8(+) T cells to evoke effective cytotoxic antitumor responses. Using in vitro and in vivo models, we investigated the molecular pathways underlying the CTLA-4-mediated differentiation of IL-17-producing CD8(+) T cells (Tc17 cells) that strongly impairs cytotoxicity. Our studies demonstrate that Tc17 cells lacking CTLA-4 signaling have limited production of STAT3-target gene products such as IL-17, IL-21, IL-23R and RORγt...
2017: Oncoimmunology
Yuan Kong, Yu-Tong Wang, Xie-Na Cao, Yang Song, Yu-Hong Chen, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang
BACKGROUND: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, whether abnormalities of T cell subsets in the bone marrow (BM) immune microenvironment, including Th17, Tc17, Th1, Tc1, Th2, Tc2 cells and regulatory T cells (Tregs), are involved in the pathogenesis of PGF remains unclear. METHODS: This prospective nested case-control study enrolled 20 patients with PGF, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD)...
March 14, 2017: Journal of Translational Medicine
Daniela Carlos, Frederico R C Costa, Camila A Pereira, Fernanda A Rocha, Juliana N U Yaochite, Gabriela G Oliveira, Fernando S Carneiro, Rita C Tostes, Simone G Ramos, Dario S Zamboni, Niels O S Camara, Bernhard Ryffel, João S Silva
Although a correlation between polymorphisms of NOD-like receptor family-pyrin domain containing 3 (NLRP3) and predisposition to type 1 diabetes (T1D) has been identified, the potential function and activation of the NLRP3 inflammasome in T1D have not been clarified. The present study shows that non-obese diabetic mice exhibited increased NLRP3, and pro-IL-1β gene expression in pancreatic lymph nodes (PLNs). Similar increases in gene expression of NLRP3, apoptosis associated speck like protein (ASC) and pro-IL-1β were induced by multiple low doses of streptozotocin (STZ) in C57BL/6 mice...
2017: Frontiers in Immunology
Adriana Gutiérrez-Hoya, Rubén López-Santiago, Jorge Vela-Ojeda, Laura Montiel-Cervantes, Octavio Rodríguez-Cortés, Víctor Rosales-García, Vladimir Paredes-Cervantes, Raúl Flores-Mejía, Daniela Sandoval-Borrego, Martha Moreno-Lafont
CD8(+) T cells that secrete proinflammatory cytokines play a central role in exacerbation of inflammation; however, a new subpopulation of CD8 regulatory T cells has recently been characterized. This study analyzes the prominent role of these different subpopulations in the development of graft-versus-host disease (GVHD). Samples from 8 healthy donors mobilized with Filgrastim® (G-CSF) and 18 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT) were evaluated by flow cytometry. Mobilization induced an increase in Tc1 (p < 0...
2017: Journal of Immunology Research
Stalin Chellappa, Harald Hugenschmidt, Morten Hagness, Saranya Subramani, Espen Melum, Pål Dag Line, Knut-Jørgen Labori, Gro Wiedswang, Kjetil Taskén, Einar Martin Aandahl
CD8(+) T cells that express retinoic acid-related orphan receptor (ROR)γt (TC17 cells) have been shown to promote procarcinogenic inflammation and contribute to a tolerogenic microenvironment in tumors. We investigated their phenotype and functional properties in relationship to the pathogenesis of human distal bile duct cancer (DBDC). DBDC patients had an elevated level of type 17 immune responses and the frequency of CD8(+)RORγt(+) T cells (TC17 cells) was increased in peripheral blood. The CD8(+)RORγt(+) T cells represented a highly activated subset and produced IL-17A in equal amount as CD4(+)RORγt(+) T cells (TH17 cells)...
January 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
Zahra Faghih, Saeideh Sadat Shobeiri, Ali Ariafar, Mohsen Sarkarian, Shahryar Zeighami, Nazanin Nazari, Saeed Abbasi-Sarvak, Nasrollah Erfani
BACKGROUND: Cytotoxic CD8+ T cells, as essential parts of the adaptive immune system, play pivotal roles in anti-tumor immune responses. It is well documented that cytokine expression profiles and activation status of these cells during anti-tumor immune responses affect the outcome of host-tumor interaction. OBJECTIVE: To investigate the percentages of CD8+ lymphocytes and their subsets in tumor draining lymph nodes of patients with bladder cancer. METHODS: Forty-five patients with bladder cancer, candidate for radical cystectomy, were recruited...
December 2016: Iranian Journal of Immunology: IJI
Sheng Cheng, Huilong Chen, Aili Wang, Hansvin Bunjhoo, Yong Cao, Jungang Xie, Yongjian Xu, Weining Xiong
INTRODUCTION: Tc17 cells are interleukin (IL)-17-producing CD8(+) T cells and have been found to participate in the development of allergic asthma. Interleukin-23 is a cytokine that may be involved in modulating the IL-17 response via Th17 cells. This study aimed to investigate whether IL-23 also has immunomodulatory effects on Tc17 cells. MATERIAL AND METHODS: An allergic asthmatic mouse model was induced by sensitizing and challenging with ovalbumin (OVA). Anti-IL-23 antibody was administered intratracheally before challenge to the OVA-induced asthmatic mouse model...
December 1, 2016: Archives of Medical Science: AMS
Ling Wang, Peng Zhao, Lingling Song, Fahong Yan, Chunlei Shi, Ying Li, Mingzhe Han, Ketao Lan
Acute graft-versus-host disease (aGVHD) is associated with an immune dysregulation usually mediated by T lymphocytes. Recently, IL-17-producing T cells including Th17 and Tc17 cells have been implicated in immune-related diseases. However, their roles in aGVHD remain uncertain. In the study, we analyzed IL-17-producing cell recovery and association with the occurrence of aGVHD. While Th17 cells steadily recovered, Tc17 cell numbers remained unaltered during the first 3months after transplantation. Occurrence of aGVHD was correlated with increased level of Tc17 cells at the second months after allo-SCT...
December 2016: International Immunopharmacology
Kelli P A MacDonald, Geoffrey R Hill, Bruce R Blazar
With the increasing use of mismatched, unrelated, and granulocyte colony-stimulating factor-mobilized peripheral blood stem cell donor grafts and successful treatment of older recipients, chronic graft-versus-host disease (cGVHD) has emerged as the major cause of nonrelapse mortality and morbidity. cGVHD is characterized by lichenoid changes and fibrosis that affects a multitude of tissues, compromising organ function. Beyond steroids, effective treatment options are limited. Thus, new strategies to both prevent and treat disease are urgently required...
January 5, 2017: Blood
Azumi Ueyama, Chihiro Imura, Yasuyuki Fusamae, Kenichiro Tsujii, Yoko Furue, Miwa Aoki, Minoru Suzuki, Tomohiko Okuda, Itsuki Oshima, Kiyoshi Yasui, Michitaka Shichijo, Mina Yamamoto
BACKGROUND: Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders and is accompanied by erythematous scaly plaques. There is growing evidence that the IL-23/Th17 axis plays a critical role in development of the disease. It was recently shown that in addition to CD4(+) Th17 cells, various IL-17-producing cell subsets such as CD8(+) Tc17 cells, dermal γδ T cells, and innate lymphoid cells are also involved in the development of psoriatic inflammation in humans...
January 2017: Journal of Dermatological Science
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, Cynthia R Giver, Edmund K 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 multiagent 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 nonhuman primate (NHP) model to interrogate the transcriptional signature of T cells during breakthrough acute graft-versus-host disease (GVHD) that occurs in the setting of clinically relevant immune suppression and compared this to the hyperacute GVHD, which develops in unprophylaxed or suboptimally prophylaxed transplant recipients...
November 24, 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...
November 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
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