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Autoimmunity t cell

Afshin Shirkani, Mohammad Shahrooei, Gholamreza Azizi, Hassan Rokni-Zadeh, Hassan Abolhassani, Shokrollah Farrokhi, Glynis Frans, Xavier Bossuyt, Asghar Aghamohammadi
ZAP-70 deficiency is a rare autosomal recessive form of combined immunodeficiency (CID) characterized by selective absence of circulating CD8 T cells with low, normal, or increased CD4 T cells in peripheral blood. Up to now, 14 unique mutations in the ZAP70 gene have been identified in patients with ZAP-70-related CID. We present a 3-year-old boy with a history of recurrent bacterial infections and autoimmunity. Initial laboratory findings showed a normal total lymphocyte count, but low levels of CD8 and CD4 T cells and an abnormal lymphocyte proliferation response...
October 19, 2016: Immunological Investigations
Gareth W Jones, David G Hill, Simon A Jones
Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules...
2016: Frontiers in Immunology
Chihiro Fujii, Takayuki Kondo, Hirofumi Ochi, Yoichiro Okada, Yuichiro Hashi, Tetsuya Adachi, Masaharu Shin-Ya, Sadayuki Matsumoto, Ryosuke Takahashi, Masanori Nakagawa, Toshiki Mizuno
Multiple sclerosis (MS) is a T cell-mediated autoimmune disease. Fingolimod, a highly effective disease-modifying drug for MS, retains CCR7(+) central memory T cells in which autoaggressive T cells putatively exist, in secondary lymphoid organs, although relapse may still occur in some patients. Here, we analyzed the T cell phenotypes of fingolimod-treated, fingolimod-untreated patients, and healthy subjects. The frequency of CD56(+) T cells and granzyme B-, perforin-, and Fas ligand-positive T cells significantly increased during fingolimod treatment...
October 18, 2016: Scientific Reports
Mathew Clement, James A Pearson, Stephanie Gras, Hugo A van den Berg, Anya Lissina, Sian Llewellyn-Lacey, Mark D Willis, Tamsin Dockree, James E McLaren, Julia Ekeruche-Makinde, Emma Gostick, Neil P Robertson, Jamie Rossjohn, Scott R Burrows, David A Price, F Susan Wong, Mark Peakman, Ania Skowera, Linda Wooldridge
CD8(+) T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8(+) T-cell population are not desirable because the associated lack of specificity can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8(+) T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-specific CD8(+) T-cells are relatively CD8-independent...
October 17, 2016: Scientific Reports
Martina Gatzka
Tumor necrosis factor alpha (TNF-α) and Interleukin 17 (IL-17) are key cytokines driving psoriasis and other inflammatory autoimmune diseases and thus represent effective targets for anti-psoriatic therapy. In a recent issue of The Journal of Pathology, Leite Dantas et al. explore a mouse model of TNF-mediated psoriasiform dermatitis and arthritis with Doxycyclin-inducible general over-expression of human TNF (ihTNFtg mice) for the contributions of macrophages and T cells in skin inflammation - with some unexpected and interesting findings...
October 17, 2016: Journal of Pathology
Joachim R Kalden
Diverse strategies to develop novel treatments for rheumatoid arthritis which specifically target those patients who do not respond to available medications, including biologics, are currently being explored. New potential therapeutic approaches which may become available as part of standard therapeutic regimens include the propagation of regulatory T cells and-in the future-of regulatory B cells. New biologic disease-modifying antirheumatic drugs (b-DMARDs) against interleukin-17 and -6, granulocyte-macrophage colony-stimulating factor, and complement component 5 are now standard components of clinical treatment programs...
June 2016: Rheumatol Ther
Lorenza Rattazzi, Giuseppa Piras, Samuel Brod, Koval Smith, Masahiro Ono, Fulvio D'Acquisto
T cells are known to be plastic and to change their phenotype according to the cellular and biochemical milieu they are embedded in. In this study, we transposed this concept at a macroscopic level assessing whether changes in the environmental housing conditions of C57/BL6 mice would influence the phenotype and function of T cells. Our study shows that exposure to 2 weeks in an enriched environment (EE) does not impact the T cell repertoire in vivo and causes no changes in the early TCR-driven activation events of these cells...
2016: Frontiers in Immunology
Chantal Kuhn, Rafael M Rezende, Andre Pires da Cunha, Fabrice Valette, Francisco J Quintana, Lucienne Chatenoud, Howard L Weiner
CD3-specific monoclonal antibody (mAb) treats autoimmune disease in animal models and has shown promise in clinical trials of type 1 diabetes. Whereas intravenous administration of CD3-specific mAb acts primarily by transient depletion of activated effector T cells, oral CD3-specific mAb acts primarily by the induction Tregs. We investigated whether oral CD3-specific mAb inhibits disease in non obese diabetic (NOD) mice that spontaneously develop autoimmune diabetes, closely resembling human type 1 diabetes...
October 10, 2016: Journal of Autoimmunity
Eoin F McKinney, Kenneth Gc Smith
T cell exhaustion represents a continuous spectrum of cellular dysfunction induced during chronic viral infection, facilitating viral persistence and associating with poor clinical outcome. Modulation of T cell exhaustion can restore function in exhausted CD8 T cells, promoting viral clearance. Exhaustion has also been implicated as playing an important role in anti-tumour responses, whereby exhausted tumour-infiltrating lymphocytes fail to control tumour progression. More recently exhaustion has been linked to long-term clinical outcome in multiple autoimmune diseases but, in contrast to cancer or infection, it is associated with a favourable clinical outcome characterised by fewer relapses...
October 13, 2016: Current Opinion in Immunology
Arshad Khan, Robert L Hunter, Chinnaswamy Jagannath
Mesenchymal stem cells (MSCs) are non-hematopoietic cells that occur in almost all human tissues and can be cultured and expanded to large numbers in vitro. They secrete growth factors, cytokines, and chemokines and express Toll-like receptors on their surface, although multiple cell biological mechanisms remain unclear. MSCs are multi-potent and can differentiate into many cell types including adipocytes, neuronal cells and osteoclasts. Despite gaps in cell biology, because of their immunomodulatory and regenerative capacity, several hundred clinical trials have used MSCs for therapy of cancer, autoimmune diseases and control of inflammation during organ transplantation...
September 28, 2016: Tuberculosis
Juncal Fernández-Orth, Petra Ehling, Tobias Ruck, Susann Pankratz, Majella-Sophie Hofmann, Peter Landgraf, Daniela C Dieterich, Karl-Heinz Smalla, Thilo Kähne, Guiscard Seebohm, Thomas Budde, Heinz Wiendl, Stefan Bittner, Sven G Meuth
K2P 5.1 channels (also called TASK-2 or KCNK5) have already been shown to be relevant in the pathophysiology of autoimmune disease since they are known to be upregulated on peripheral and central T lymphocytes of multiple sclerosis (MS) patients. Moreover, overexpression of K2P 5.1 channels in vitro provokes enhanced T-cell effector functions. However, the molecular mechanisms regulating intracellular K2P 5.1 channel trafficking are unknown so far. Thus, the aim of the study is to elucidate the trafficking of K2P 5...
October 15, 2016: Traffic
M Daves, J Blecken, T Matthias, A Frey, V Perkmann, A Dall Acqua, A Joos, S Platzgummer
The IIF using the HEp-2 cell substrate should be still considered the "gold standard" techniques for determination of antinuclear antibody (ANA). Standardization and automation can be considered to be still in progress. Aim of this study was to evaluate the performance of the commercially automated indirect immunofluorescent antinuclear HEp-2 antibody assay. The study was designed to compare two commercially available HEp-2 ANA by indirect immunofluorescent antibody assays using a sensitivity panel (120 clinically determined patients) and a specificity panel consisting of 78 clinically confirmed negative patients...
October 14, 2016: Immunologic Research
Caroline Stienne, Michaël F Michieletto, Mehdi Benamar, Nadège Carrié, Isabelle Bernard, Xuan-Hung Nguyen, Yannick Lippi, Fanny Duguet, Roland S Liblau, Stephen M Hedrick, Abdelhadi Saoudi, Anne S Dejean
The transcription factor Foxo3 plays a crucial role in myeloid cell function but its role in lymphoid cells remains poorly defined. Here, we have shown that Foxo3 expression was increased after T cell receptor engagement and played a specific role in the polarization of CD4(+) T cells toward pathogenic T helper 1 (Th1) cells producing interferon-γ (IFN-γ) and granulocyte monocyte colony stimulating factor (GM-CSF). Consequently, Foxo3-deficient mice exhibited reduced susceptibility to experimental autoimmune encephalomyelitis...
October 1, 2016: Immunity
Yu-Shu Huang, Christian Guilleminault, Fang-Ming Hwang, Chuan Cheng, Cheng-Hui Lin, Hsueh-Yu Li, Li-Ang Lee
Pediatric obstructive sleep apnea (OSA) is associated with chronic systemic inflammation and with cognitive impairments. This study aimed to investigate the status of proinflammatory cytokines, particularly interleukin 17 (IL-17) and interleukin 23 (IL-23) and cognition in pediatric OSA.Controls and OSA children participated in the study. Exclusion criteria were adenotonsillectomy, heart, neurological and severe psychiatric diseases, craniofacial syndromes, and obesity. Polysomnogram was followed by serum testing for inflammatory markers and neurocognitive tests such as continuous performance task (CPT) and Wisconsin card sorting test, questionnaires, analyses of plasma high-sensitivity C-reactive protein (HS-CRP), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), IL-17, and IL-23...
October 2016: Medicine (Baltimore)
Rahul Krishnan, David Ko, Clarence E Foster, Wendy Liu, A M Smink, Bart de Haan, Paul De Vos, Jonathan R T Lakey
Transplantation of alginate-encapsulated islets has the potential to treat patients suffering from type I diabetes, a condition characterized by an autoimmune attack against insulin-secreting beta cells. However, there are multiple immunological challenges associated with this procedure, all of which must be adequately addressed prior to translation from trials in small animal and nonhuman primate models to human clinical trials. Principal threats to graft viability include immune-mediated destruction triggered by immunogenic alginate impurities, unfavorable polymer composition and surface characteristics, and release of membrane-permeable antigens, as well as damage associated molecular patterns (DAMPs) by the encapsulated islets themselves...
2017: Methods in Molecular Biology
Keshav Raj Sigdel, Lihua Duan, Yin Wang, Weiping Hu, Ning Wang, Qingyi Sun, Qingyan Liu, Xiaocong Liu, Xianghua Hou, Ao Cheng, Guixiu Shi, Yanlin Zhang
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control...
2016: Mediators of Inflammation
Brandon Coder, Weikan Wang, Liefeng Wang, Zhongdao Wu, Qichuan Zhuge, Dong-Ming Su
The interaction between T cells and the central nervous system (CNS) in homeostasis and injury has been recognized being both pathogenic (CD4+ T-helper 1 - Th1, Th17 and γδT) and ameliorative (Th2 and regulatory T cells - Tregs). However, in-depth studies aimed to elucidate the precise in the aged microenvironment and the dichotomous role of Tregs have just begun and many aspects remain unclear. This is due, not only to a mutual dependency and reciprocal causation of alterations and diseases between the nervous and T cell immune systems, but also to an inconsistent aging of the two systems, which dynamically changes with CNS injury/recovery and/or aging process...
October 11, 2016: Oncotarget
Young Uk Kim, Byung-Seok Kim, Hoyong Lim, Rick A Wetsel, Yeonseok Chung
CXCR5⁺ T follicular helper (Tfh) cells are associated with aberrant autoantibody production in patients with antibody-mediated autoimmune diseases including lupus. Follicular regulatory T (Tfr) cells expressing CXCR5 and Bcl6 have been recently identified as a specialized subset of Foxp3⁺ regulatory T (Treg) cells that control germinal center reactions. In this study, we show that retroviral transduction of CXCR5 gene in Foxp3⁺ Treg cells induced a stable expression of functional CXCR5 on their surface...
October 17, 2016: Biomolecules & Therapeutics
O I Afanas'eva, E A Pylaeva, E A Klesareva, A V Potekhina, S I Provatorov, M I Afanas'eva, T L Krasnikova, V P Masenko, T I Aref'eva, S N Pokrovsky
AIM: To study the role of lipoprotein(a) [Lp(a)] as a potential autoantigen causing the activation of immunocompetent cells in atherosclerosis. SUBJECTS AND METHODS: A total of 104 men with stable coronary artery (CA) disease and different degrees of progressive coronary atherosclerosis were examined. Clinical blood analysis was carried out and lymphocyte subpopulations (CD4+, Th1, Th17, and Treg) were determined using immunofluorescence and flow cytometry. In addition, the indicators of blood lipid composition, Lp(a), autoantibody (autoAb) titer to Lp(a), and low-density lipoproteins (LDL), and the lymphocyte activation marker sCD25 were also measured...
2016: Terapevticheskiĭ Arkhiv
Mei Song, Xiaojing Ma
Interleukin-35 (IL-35) is the latest addition to the IL-12 family of heterodimeric cytokines, consisting of IL-12 p35 subunit and IL-27β subunit Epstein-Barr virus induced 3 (EBI3). Since its discovery, IL-35 has been shown to exhibit immunosuppressive activities which are distinct from other members of IL-12 family. IL-35 is also unique in that it is expressed primarily by regulatory T-cells (Tregs) rather than by antigen-presenting cells (APCs). IL-35 can directly suppress effector T-cell proliferation and function and inhibit the differentiation of Th17 cells...
2016: Advances in Experimental Medicine and Biology
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