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Type 1 diabetes regulatory T lymphocyte

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https://www.readbyqxmd.com/read/27903296/factors-affecting-long-term-efficacy-of-t-regulatory-cell-based-therapy-in-type-1-diabetes
#1
Natalia Marek-Trzonkowska, Małgorzata Myśliwiec, Dorota Iwaszkiewicz-Grześ, Mateusz Gliwiński, Ilona Derkowska, Magdalena Żalińska, Maciej Zieliński, Marcelina Grabowska, Hanna Zielińska, Karolina Piekarska, Anna Jaźwińska-Curyłło, Radosław Owczuk, Agnieszka Szadkowska, Krystyna Wyka, Piotr Witkowski, Wojciech Młynarski, Przemysława Jarosz-Chobot, Artur Bossowski, Janusz Siebert, Piotr Trzonkowski
BACKGROUND: Recent studies suggest that immunotherapy using T regulatory cells (Tregs) prolongs remission in type 1 diabetes (T1DM). Here, we report factors that possibly affect the efficacy of this treatment. METHODS: The metabolic and immune background of 12 children with recently diagnosed T1DM, as well as that of untreated subjects, during a 2-year follow-up is presented. Patients were treated with up to 30 × 10(6)/kg b.w. of autologous expanded CD3(+)CD4(+)CD25(high)CD127(-) Tregs...
December 1, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/27797910/islet-expressed-cxcl10-promotes-autoimmune-destruction-of-islet-iso-grafts-in-mice-with-type-1-diabetes
#2
Christine Bender, Selina Christen, Klaus Scholich, Monika Bayer, Josef M Pfeilschifter, Edith Hintermann, Urs Christen
Type 1 diabetes (T1D) results from the autoimmune destruction of insulin-producing β-cells in the pancreas. Thereby the chemokine CXC-motif ligand 10 (CXCL10) plays an important role in the recruitment of autoaggressive lymphocytes to the islets of Langerhans. Transplantation of isolated islets as a promising therapy of T1D has been hampered by early graft rejection. Here, we investigated the influence of CXCL10 on the autoimmune destruction of islet iso-grafts using RIP-LCMV mice expressing a lymphocytic choriomeningitis virus (LCMV) protein in the β-cells...
October 26, 2016: Diabetes
https://www.readbyqxmd.com/read/27764529/t-lymphocyte-and-glycemic-status-after-vitamin-d-treatment-in-type-1-diabetes-a-randomized-controlled-trial-with-sequential-cross-over
#3
D Bogdanou, M Penna-Martinez, N Filmann, T L Chung, Y Moran-Auth, J Wehrle, C Cappel, S Huenecke, E Herrmann, U Koehl, K Badenhoop
BACKGROUND: Type 1 diabetes mellitus (T1D) is mediated by autoaggressive T effector cells with an underlying regulatory T cell (Treg) defect. Vitamin D (VD) deficiency is highly prevalent in T1D which can aggravate immune dysfunction. High dose VD treatment may enhance Tregs and improve metabolism in T1D patients. METHODS: In a randomized, double-blind, placebo-controlled trial with cross-over design, patients received either for three months cholecalciferol 4000 IU/d, followed by three months placebo or the sequential alternative...
October 20, 2016: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/27629840/abnormal-distribution-of-gamma-delta-t-lymphocytes-and-their-subsets-in-type-1-diabetes
#4
Agnieszka Zubkiewicz-Kucharska, Anna Noczyńska
BACKGROUND: It was assumed that T γδ lymphocytes (T γδ) are involved in the autoimmune destruction of beta cells, presumably as regulatory cells. OBJECTIVES: The aim of this paper was to investigate T γδ cells mean percentage (%) in peripheral blood in patients with type 1 diabetes (T1DM) at the time of diagnosis and after twelve months of observation. MATERIAL AND METHODS: A total of 41 patients (21 boys, 51.2%) with new-onset T1DM were included...
July 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/27615679/coincidence-of-ptpn22-c-1858cc-and-fcrl3-169cc-genotypes-as-a-biomarker-of-preserved-residual-%C3%AE-cell-function-in-children-with-type-1-diabetes
#5
Małgorzata Pawłowicz, Rafał Filipów, Grzegorz Krzykowski, Anna Stanisławska-Sachadyn, Lucyna Morzuch, Julia Kulczycka, Anna Balcerska, Janusz Limon
BACKGROUND: Genotype-phenotype studies in type 1 diabetes (T1DM) patients are needed for further development of therapy strategies. OBJECTIVE: Our aims were to investigate the distribution of selected PTPN22 and FCRL3 gene polymorphisms and their associations with clinical course of disease in children with newly diagnosed T1DM from the Pomeranian region of Poland. SUBJECTS/METHODS: The prospective, longitudinal study of 147 children with newly diagnosed T1DM-autoimmune subtype was conducted...
September 12, 2016: Pediatric Diabetes
https://www.readbyqxmd.com/read/27560779/t-regulatory-lymphocytes-in-type-1-diabetes-impaired-cd25-expression-and-il-2-induced-stat5-phosphorylation-in-pediatric-patients
#6
Zuzana Parackova, Jana Kayserova, Klara Danova, Kristyna Sismova, Eva Dudkova, Zdenek Sumnik, Stanislava Kolouskova, Jan Lebl, Katerina Stechova, Anna Sediva
T regulatory cells (Tregs) are essential for maintaining tolerance and preventing autoimmune diseases, such as type 1 diabetes (T1D). In our study, we investigated CD25 + FoxP3 + Tregs and thymic FoxP3 + Helios + Tregs in large cohorts of children with T1D at onset and with long-term T1D, and further in their relatives and healthy controls. We observed significantly decreased numbers of CD25 + FoxP3 + Tregs, but not FoxP3 + Helios + Tregs, in long-term patients compared with the control group and T1D onset...
August 25, 2016: Autoimmunity
https://www.readbyqxmd.com/read/27498109/changes-of-regulatory-t-cells-transforming-growth-factor-beta-and-interleukin-10-in-patients-with-type-1-diabetes-mellitus-a-systematic-review-and-meta-analysis
#7
REVIEW
Yong-Chao Qiao, Jian Shen, Xue-Zhi Hong, Ling Liang, Chao-Sheng Bo, Yi Sui, Hai-Lu Zhao
Regulatory T lymphocyte cells (Treg) associated with interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) have implicated in the development of type 1 diabetes mellitus (T1DM), yet the existing evidence remains unclear. Hereby we performed a systematic review and meta-analysis to characterize the changes in T1DM patients. A total of 1407 T1DM patients and 1373 healthy controls from 40 case-control studies were eventually included in the pooling analysis. Compared with the controls, T1DM patients had decreased frequency of CD4(+)CD25(+)Treg (p=0...
September 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27318739/a-unique-cd8-t-lymphocyte-signature-in-pediatric-type-1-diabetes
#8
Yamina Hamel, François-Xavier Mauvais, Hang-Phuong Pham, Roland Kratzer, Christophe Marchi, Émilie Barilleau, Emmanuelle Waeckel-Enée, Jean-Baptiste Arnoux, Agnès Hartemann, Corinne Cordier, Jerome Mégret, Benedita Rocha, Pascale de Lonlay, Jacques Beltrand, Adrien Six, Jean-Jacques Robert, Peter van Endert
Human type 1 diabetes results from a destructive auto-reactive immune response in which CD8(+) T lymphocytes play a critical role. Given the intense ongoing efforts to develop immune intervention to prevent and/or cure the disease, biomarkers suitable for prediction of disease risk and progress, as well as for monitoring of immunotherapy are required. We undertook separate multi-parameter analyses of single naïve and activated/memory CD8(+) T lymphocytes from pediatric and adult patients, with the objective of identifying cellular profiles associated with onset of type 1 diabetes...
September 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/27133873/lower-omental-t-regulatory-cell-count-is-associated-with-higher-fasting-glucose-and-lower-%C3%AE-cell-function-in-adults-with-obesity
#9
Lauren E Gyllenhammer, Jonathan Lam, Tanya L Alderete, Hooman Allayee, Omid Akbari, Namir Katkhouda, Michael I Goran
OBJECTIVE: T-lymphocytes are potential initiators and regulators of adipose tissue (AT) inflammation, but there is limited human data on omental AT. The aim of this study was to assess the relationship between T cells, particularly Foxp3+ regulatory T (Treg) cells, in human subcutaneous (subQ) and omental AT and type 2 diabetes risk. METHODS: SubQ and deep subQ (DsubQ) abdominal and omental AT biopsies were collected from 44 patients (body mass index, BMI ≥25) undergoing elective abdominal surgery...
June 2016: Obesity
https://www.readbyqxmd.com/read/27003655/-effect-of-roux-en-y-gastric-bypass-on-the-short-term-immune-function-in-patients-with-type-2-diabetes-mellitus
#10
Lihai Zhang, Bin Xia, Jiao Wang, Xiaoping Lyu, Yuesheng Wang, Wenli Huang, Baihong Tan, Hong Deng, Yanbin Yin
OBJECTIVE: To investigate the effect of laparoscopic Roux-en-Y gastric bypass on the short-term immune function of type 2 diabetic patients and to explore the correlation between the immune regulatory effect and blood glucose control. METHODS: Clinical data of 28 patients with type 2 diabetes mellitus who underwent laparoscopic Roux-en-Y gastric bypass surgery in our hospital during January 2014 to January 2015 were retrospectively collected. Fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), immunoglobulin (IgG, IgA, IgM), T lymphocytes CD3(+), killer T cells CD3(+)CD8(+), helper T cells CD3(+)CD4(+), natural killer(NK) cell subsets CD16(+),CD56(+) and B cell subsets CD19(+),CD45(+) levels were detected and compared between before and after surgery...
March 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/26816588/role-of-alteration-in-treg-th17-cells-balance-in-nephropathic-patients-with-type-2-diabetes-mellitus
#11
Sameh Abouzeid, Nevine Sherif
INTRODUCTION: In type 2 diabetes mellitus, the adaptive immune system drives systemic inflammation, promoting insulin resistance and related complications, such as diabetic nephropathy. Increased infiltration of activated T lymphocytes has been found in patients with diabetic nephropathy. T-cell influx and accumulation are the factors that aggravate diabetic nephropathy and link with glomerular filtration surface and albumin excretion. An appropriate balance between pro-inflammatory (T helper 17: Th17, and T helper 1: Th1) and anti-inflammatory (regulatory T cells: Tregs) subsets of T cells is critical to maintain homeostasis and avoid inflammatory disease...
December 2015: Electronic Physician
https://www.readbyqxmd.com/read/26680606/restoration-of-t-cell-substes-of-patients-with-type-1-diabetes-mellitus-by-microencapsulated-human-umbilical-cord-wharton-jelly-derived-mesenchymal-stem-cells-an-in-vitro-study
#12
Pia Montanucci, Alessia Alunno, Giuseppe Basta, Onelia Bistoni, Teresa Pescara, Sara Caterbi, Ilaria Pennoni, Vittorio Bini, Roberto Gerli, Riccardo Calafiore
Human umbilical cord Wharton jelly-derived mesenchymal stem cells (hUCMS) might apply to treating chronic autoimmune disorders, as already shown for Sjögren's syndrome, including type 1 diabetes mellitus (T1D). Since naked hUCMS grafts encountered restraints, we enveloped hUCMS, within immunoisolatory microcapsules (CpS-hUCMS), made of our endotoxin-free, clinical grade alginate. We then examined the vitro effects of interferon (IFN)-γ-pretreated CpS-hUCMS on Th17 and Treg of T1D patients (n=15) and healthy controls (n=10)...
February 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/26674203/inhibition-of-autoimmune-diabetes-in-nod-mice-by-mirna-therapy
#13
Duncheng Wang, Iryna Shanina, Wendy M Toyofuku, Marc S Horwitz, Mark D Scott
Autoimmune destruction of the pancreatic islets in Type 1 diabetes is mediated by both increased proinflammatory (Teff) and decreased regulatory (Treg) T lymphocytes resulting in a significant decrease in the Treg:Teff ratio. The non-obese diabetic (NOD) mouse is an excellent in vivo model for testing potential therapeutics for attenuating the decrease in the Treg:Teff ratio and inhibiting disease pathogenesis. Here we show for the first time that a bioreactor manufactured therapeutic consisting of a complex of miRNA species (denoted as TA1) can effectively reset the NOD immune system from a proinflammatory to a tolerogenic state thus preventing or delaying autoimmune diabetes...
2015: PloS One
https://www.readbyqxmd.com/read/26646829/protocol-of-the-adaptive-study-of-il-2-dose-frequency-on-regulatory-t-cells-in-type-1-diabetes-dilfrequency-a-mechanistic-non-randomised-repeat-dose-open-label-response-adaptive-study
#14
Lucy A Truman, Marcin L Pekalski, Paula Kareclas, Marina Evangelou, Neil M Walker, James Howlett, Adrian P Mander, Jane Kennet, Linda S Wicker, Simon Bond, John A Todd, Frank Waldron-Lynch
INTRODUCTION: Type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing β cells in the pancreatic islets, leading to insulinopenia and hyperglycaemia. Genetic analyses indicate that alterations of the interleukin-2 (IL-2) pathway mediating immune activation and tolerance predispose to T1D, specifically the polymorphic expression of the IL-2 receptor-α chain (CD25) on T lymphocytes. Replacement of physiological doses of IL-2 could restore self-tolerance and prevent further autoimmunity by enhancing the function of CD4(+) T regulatory cells (Tregs) to limit the activation of auto reactive T effector cells (Teffs)...
December 8, 2015: BMJ Open
https://www.readbyqxmd.com/read/26644313/a-patient-with-ctla-4-haploinsufficiency-presenting-gastric-cancer
#15
Seiichi Hayakawa, Satoshi Okada, Miyuki Tsumura, Sonoko Sakata, Yoshitaka Ueno, Kohsuke Imai, Tomohiro Morio, Osamu Ohara, Kazuaki Chayama, Masao Kobayashi
Cytotoxic T-lymphocyte-antigen 4 (CTLA-4) is an essential negative regulator expressed on regulatory T cells (Tregs) and activated T cells. Germline heterozygous mutations in CTLA4 lead to haploinsufficiency of CTLA-4, resulting in the development of an autosomal dominant immune dysregulation syndrome with incomplete penetrance. We report here a Japanese patient with this disorder who has a novel heterozygous single nucleotide insertion, 76_77insT (p. L28SfsX40), in the CTLA4 gene. Peripheral blood mononuclear cells from the patient showed decreased frequency of CTLA-4(high) cells in CD4(+)FOXP3(+) cells following CD3/CD28 stimulation...
January 2016: Journal of Clinical Immunology
https://www.readbyqxmd.com/read/26293506/anti-cd3-anti-cxcl10-antibody-combination-therapy-induces-a-persistent-remission-of-type-1-diabetes-in-two-mouse-models
#16
COMPARATIVE STUDY
Stanley Lasch, Peter Müller, Monika Bayer, Josef M Pfeilschifter, Andrew D Luster, Edith Hintermann, Urs Christen
Anti-CD3 therapy of type 1 diabetes results in a temporary halt of its pathogenesis but does not constitute a permanent cure. One problem is the reinfiltration of islets of Langerhans with regenerated, autoaggressive lymphocytes. We aimed at blocking such a reentry by neutralizing the key chemokine CXCL10. Combination therapy of diabetic RIP-LCMV and NOD mice with anti-CD3 and anti-CXCL10 antibodies caused a substantial remission of diabetes and was superior to monotherapy with anti-CD3 or anti-CXCL10 alone...
December 2015: Diabetes
https://www.readbyqxmd.com/read/26220361/the-big-bang-in-obese-fat-events-initiating-obesity-induced-adipose-tissue-inflammation
#17
REVIEW
Felix M Wensveen, Sonja Valentić, Marko Šestan, Tamara Turk Wensveen, Bojan Polić
Obesity is associated with the accumulation of pro-inflammatory cells in visceral adipose tissue (VAT), which is an important underlying cause of insulin resistance and progression to diabetes mellitus type 2 (DM2). Although the role of pro-inflammatory cytokines in disease development is established, the initiating events leading to immune cell activation remain elusive. Lean adipose tissue is predominantly populated with regulatory cells, such as eosinophils and type 2 innate lymphocytes. These cells maintain tissue homeostasis through the excretion of type 2 cytokines, such as IL-4, IL-5, and IL-13, which keep adipose tissue macrophages (ATMs) in an anti-inflammatory, M2-like state...
September 2015: European Journal of Immunology
https://www.readbyqxmd.com/read/26136917/treatment-with-incomplete-freund-s-adjuvant-and-listeria-monocytogenes-delays-diabetes-via-an-interleukin-17-secretion-independent-pathway
#18
Hai-Ping Wang, Zhi-Gao He
Non-obese diabetes (NOD) mice are widely used as an animal model in studies of type I diabetes (TID). Treatment with complete Freund's adjuvant (CFA) in pro-diabetic NOD mice is known to inhibit disease progression by activating CD1d-specific natural killer (NK) T cells and inducing interleukin (IL)-17 secretion in innate immune cells. The aim of the present study was to examine the effect of incomplete Freund's adjuvant (IFA) and L. monocytogenes treatment on the development of TID in NOD mice. This combined treatment of IFA and L...
May 2015: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/26076454/induction-of-tolerogenic-dendritic-cells-by-a-pegylated-tlr7-ligand-for-treatment-of-type-1-diabetes
#19
Tomoko Hayashi, Shiyin Yao, Brian Crain, Victor J Promessi, Luke Shyu, Caroline Sheng, McNancy Kang, Howard B Cottam, Dennis A Carson, Maripat Corr
Autoimmune diabetes mellitus (DM) results from the destruction of pancreatic islet cells by activated T lymphocytes, which have been primed by activated dendritic cells (DC). Individualized therapy with ex vivo DC manipulation and reinfusion has been proposed as a treatment for DM, but this treatment is limited by cost, and requires specialized facilities. A means of in situ modulation of the DC phenotype in the host would be more accessible. Here we report a novel innate immune modulator, 1Z1, generated by conjugating a TLR7 ligand to six units of polyethylene glycol (PEG), which skews DC phenotype in vivo...
2015: PloS One
https://www.readbyqxmd.com/read/25896969/multiple-mechanisms-involved-in-diabetes-protection-by-lipopolysaccharide-in-non-obese-diabetic-mice
#20
Jun Wang, Hui Cao, Hongjie Wang, Guoxiao Yin, Jiao Du, Fei Xia, Jingli Lu, Ming Xiang
Toll-like receptor 4 (TLR4) activation has been proposed to be important for islet cell inflammation and eventually β cell loss in the course of type 1 diabetes (T1D) development. However, according to the "hygiene hypothesis", bacterial endotoxin lipopolysaccharide (LPS), an agonist on TLR4, inhibits T1D progression. Here we investigated possible mechanisms for the protective effect of LPS on T1D development in non-obese diabetic (NOD) mice. We found that LPS administration to NOD mice during the prediabetic state neither prevented nor reversed insulitis, but delayed the onset and decreased the incidence of diabetes, and that a multiple-injection protocol is more effective than a single LPS intervention...
June 15, 2015: Toxicology and Applied Pharmacology
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