The frequency and immunodominance of islet-specific CD8+ T-cell responses change after type 1 diabetes diagnosis and treatment.

Abstract:

OBJECTIVE:Islet-reactive CD8(+) T-cells play a key role in the pathogenesis of type 1 diabetes in the NOD mouse. The predominant T-cell specificities change over time, but whether similar shifts also occur after clinical diagnosis and insulin treatment in type 1 diabetic patients is unknown. RESEARCH DESIGN AND METHODS:We took advantage of a recently validated islet-specific CD8(+) T-cell gamma-interferon enzyme-linked immunospot (ISL8Spot) assay to follow responses against preproinsulin (PPI), GAD, insulinoma-associated protein 2 (IA-2), and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) epitopes in 15 HLA-A2(+) adult type 1 diabetic patients close to diagnosis and at a second time point 7-16 months later. RESULTS:CD8(+) T-cell reactivities were less frequent at follow-up, as 28.6% of responses tested positive at type 1 diabetes diagnosis vs. 13.2% after a median of 11 months (P = 0.003). While GAD and IA-2 autoantibody (aAb) titers were unchanged in 75% of cases, the fraction of patients responding to PPI and/or GAD epitopes by ISL8Spot decreased from 60-67 to 20% (P < 0.02). The previously subdominant IA-2(206-214) and IGRP(265-273) peptides were newly targeted, thus becoming the immunodominant epitopes. CONCLUSIONS:Shifts both in frequency and in immunodominance of CD8(+) T-cell responses occur more rapidly than do changes in aAb titers. These different kinetics may suggest complementary clinical applications for T-cell and aAb measurements.

journal_name

Diabetes

journal_title

Diabetes

authors

Martinuzzi E,Novelli G,Scotto M,Blancou P,Bach JM,Chaillous L,Bruno G,Chatenoud L,van Endert P,Mallone R

doi

10.2337/db07-1594

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

1312-20

issue

5

eissn

0012-1797

issn

1939-327X

pii

db07-1594

journal_volume

57

pub_type

杂志文章

相关文献

DIABETES文献大全
  • Binding of insulin to its receptor impairs recognition by monoclonal anti-insulin antibodies.

    abstract::The interaction between insulin and its receptor was investigated using both monoclonal and polyclonal anti-insulin antibodies. After covalent cross-linking of 125I-insulin to the insulin receptor on cultured human lymphocytes (IM-9 cells) using disuccinimidyl suberate, we inquired whether the insulin-receptor complex...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.8.778

    authors: Taylor SI,Schroer JA,Marcus-Samuels B,McElduff A,Bender TP

    更新日期:1984-08-01 00:00:00

  • Virus-induced murine diabetes. Enhancement by immunosuppression.

    abstract::Adult, male ICR Swiss mice are susceptible to the diabetogenic effects of the D-variant of encephalomyocarditis virus (EMC-D) in contrast to adult C3H/HeJ male mice, which are relatively resistant. To date, experimental evidence suggests that the immune system plays a role in the pathogenesis of this infection. We hav...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.12.1217

    authors: Gould CL,McMannama KG,Bigley NJ,Giron DJ

    更新日期:1985-12-01 00:00:00

  • Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24.

    abstract::This genome-wide search for susceptibility genes to type 2 diabetes/impaired glucose homeostasis (IGH) was performed on a relatively homogeneous Chinese sample with a total number of 257 pedigrees and 385 affected sibpairs. Two regions showed significant linkage to type 2 diabetes/IGH in the Chinese. The region showin...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.1.228

    authors: Xiang K,Wang Y,Zheng T,Jia W,Li J,Chen L,Shen K,Wu S,Lin X,Zhang G,Wang C,Wang S,Lu H,Fang Q,Shi Y,Zhang R,Xu J,Weng Q

    更新日期:2004-01-01 00:00:00

  • Dietary cod protein restores insulin-induced activation of phosphatidylinositol 3-kinase/Akt and GLUT4 translocation to the T-tubules in skeletal muscle of high-fat-fed obese rats.

    abstract::Diet-induced obesity is known to cause peripheral insulin resistance in rodents. We have recently found that feeding cod protein to high-fat-fed rats prevents the development of insulin resistance in skeletal muscle. In the present study, we have further explored the cellular mechanisms behind this beneficial effect o...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.52.1.29

    authors: Tremblay F,Lavigne C,Jacques H,Marette A

    更新日期:2003-01-01 00:00:00

  • Enzyme inducers improve insulin sensitivity in non-insulin-dependent diabetic subjects.

    abstract::The reduction in blood glucose in non-insulin-dependent diabetes mellitus (NIDDM) brought about by the use of phenobarbital (PB), a hepatic microsomal enzyme inducer, suggests an improvement in insulin sensitivity. The effect of PB on insulin-mediated glucose metabolism was hence investigated using the euglycemic clam...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.34.9.911

    authors: Lahtela JT,Arranto AJ,Sotaniemi EA

    更新日期:1985-09-01 00:00:00

  • T-cell costimulation protects obesity-induced adipose inflammation and insulin resistance.

    abstract::A key pathophysiologic role for activated T-cells in mediating adipose inflammation and insulin resistance (IR) has been recently postulated. However, mechanisms underlying their activation are poorly understood. In this study, we demonstrated a previously unrecognized homeostatic role for the costimulatory B7 molecul...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db13-1094

    authors: Zhong J,Rao X,Braunstein Z,Taylor A,Narula V,Hazey J,Mikami D,Needleman B,Rutsky J,Sun Q,Deiuliis JA,Satoskar AR,Rajagopalan S

    更新日期:2014-04-01 00:00:00

  • Circulating immune complexes and platelet thromboxane synthesis in patients with insulin-dependent (type I) diabetes mellitus.

    abstract::Platelets from diabetic subjects with circulating immune complexes (CIC) synthesized greater amounts of thromboxane than did platelets from CIC-negative patients or controls. In view of the known action of CIC on platelet function, a relationship between these two factors may be suggested in the initiation and progres...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.33.8.728

    authors: Triolo G,Davi' G,Giardina E,Cardella F,Meli F,La Grutta A,Strano A,Bompiani GD

    更新日期:1984-08-01 00:00:00

  • Impairment of lymphocyte-suppressive system in recent-onset insulin-dependent diabetes mellitus. Correlation with metabolic control.

    abstract::Impairment of suppressor-cell activity may be important in the pathogenesis and maintenance of insulin-dependent diabetes mellitus (IDDM). In 23 recent-onset IDDM patients, lymphocyte sensitivity in vitro to theophylline was tested both in basal conditions and after improvement of metabolic control. This pharmacologic...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.35.9.1053

    authors: Crosti F,Secchi A,Ferrero E,Falqui L,Inverardi L,Pontiroli AE,Ciboddo GF,Pavoni D,Protti P,Rugarli C

    更新日期:1986-09-01 00:00:00

  • Human apolipoprotein(a) kringle V inhibits ischemia-induced retinal neovascularization via suppression of fibronectin-mediated angiogenesis.

    abstract::Retinal neovascularization is observed in progression of diabetic retinopathy. New vessels grow into the vitreous cavity in proliferative diabetic retinopathy, resulting in traction retinal detachment and vitreous hemorrhage. To overcome the catastrophic visual loss due to these complications, efforts have been focuse...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db11-1541

    authors: Lim Y,Jo DH,Kim JH,Ahn JH,Hwang YK,Kang DK,Chang SI,Yu YS,Yoon Y,Kim JH

    更新日期:2012-06-01 00:00:00

  • Altered nephrogenesis due to maternal diabetes is associated with increased expression of IGF-II/mannose-6-phosphate receptor in the fetal kidney.

    abstract::We have recently demonstrated that the exposure to hyperglycemia in utero impairs nephrogenesis in rat fetuses (Amri K et al., Diabetes 48:2240-2245, 1999). Diabetic pregnancy is commonly associated with alterations in the IGF system in fetal tissues. It has also been shown that both IGF-I and IGF-II are produced with...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.50.5.1069

    authors: Amri K,Freund N,Duong Van Huyen JP,Merlet-Bénichou C,Lelièvre-Pégorier M

    更新日期:2001-05-01 00:00:00

  • Evidence from glut2-null mice that glucose is a critical physiological regulator of feeding.

    abstract::A role for glucose in the control of feeding has been proposed, but its precise physiological importance is unknown. Here, we evaluated feeding behavior in glut2-null mice, which express a transgenic glucose transporter in their beta-cells to rescue insulin secretion (ripglut1;glut2-/- mice). We showed that in the abs...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.55.04.06.db05-1386

    authors: Bady I,Marty N,Dallaporta M,Emery M,Gyger J,Tarussio D,Foretz M,Thorens B

    更新日期:2006-04-01 00:00:00

  • Effects of calcium antagonists on insulin-mediated glucose metabolism in skeletal muscle.

    abstract::The effect of three calcium antagonists (verapamil, diltiazem, and nifedipine) on insulin effects was investigated in isolated rat soleus muscles. Soleus muscles were incubated in the presence of insulin (100 microU/ml), a concentration that stimulates the rates of lactate formation and glycogen synthesis half-maximal...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.43.1.73

    authors: Foot EA,Leighton B

    更新日期:1994-01-01 00:00:00

  • Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model.

    abstract::The quantitative insulin-sensitivity check index (QUICKI) has an excellent linear correlation with the glucose clamp index of insulin sensitivity (SI(Clamp)) that is better than that of many other surrogate indexes. However, correlation between a surrogate and reference standard may improve as variability between subj...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.7.1914

    authors: Chen H,Sullivan G,Quon MJ

    更新日期:2005-07-01 00:00:00

  • Association of HbA1c with prevalent cardiovascular disease in the original cohort of the Framingham Heart Study.

    abstract::We studied the cross-sectional relationship between HbA1c and cardiovascular disease (CVD) in the survivors of the original cohort of the Framingham Heart Study (n = 1045). HbA1c was significantly related to prevalent CVD among women but not men. HbA1c was also related to hypertension and to the ratio of total to high...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.41.2.202

    authors: Singer DE,Nathan DM,Anderson KM,Wilson PW,Evans JC

    更新日期:1992-02-01 00:00:00

  • Differential activation of peroxisome proliferator-activated receptor-gamma by troglitazone and rosiglitazone.

    abstract::The antidiabetic thiazolidinediones, which include troglitazone and rosiglitazone, are ligands for the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-gamma and exert their antihyperglycemic effects by regulation of PPAR-gamma-responsive genes. We report here that PPAR-gamma activation by troglitazo...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.4.539

    authors: Camp HS,Li O,Wise SC,Hong YH,Frankowski CL,Shen X,Vanbogelen R,Leff T

    更新日期:2000-04-01 00:00:00

  • Cd36 and molecular mechanisms of insulin resistance in the stroke-prone spontaneously hypertensive rat.

    abstract::Insulin resistance is of pathogenic importance in several common human disorders including type 2 diabetes, hypertension, obesity and hyperlipidemia, but the underlying mechanisms are unknown. The spontaneously hypertensive rat (SHR) is a model of these human insulin resistance syndromes. Quantitative trait loci (QTLs...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.49.12.2222

    authors: Collison M,Glazier AM,Graham D,Morton JJ,Dominiczak MH,Aitman TJ,Connell JM,Gould GW,Dominiczak AF

    更新日期:2000-12-01 00:00:00

  • Defective differentiation of regulatory FoxP3+ T cells by small-intestinal dendritic cells in patients with type 1 diabetes.

    abstract:OBJECTIVE:The gut environment modulates the pathogenesis of type 1 diabetes (T1D), but how it affects autoimmunity toward pancreatic β-cells, a self-tissue located outside the intestine, is still unclear. In the small intestine, lamina propria dendritic cells (LPDCs) induce peripheral differentiation of FoxP3(+) regula...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/db10-1201

    authors: Badami E,Sorini C,Coccia M,Usuelli V,Molteni L,Bolla AM,Scavini M,Mariani A,King C,Bosi E,Falcone M

    更新日期:2011-08-01 00:00:00

  • Absolute requirement of macrophages for the development and activation of beta-cell cytotoxic CD8+ T-cells in T-cell receptor transgenic NOD mice.

    abstract::The development of autoimmune diabetes in NOD mice results from selective destruction of beta-cells by a T-cell-dependent autoimmune process. However, the mechanisms that control the generation of beta-cell cytotoxic T-cells in vivo are poorly understood. We recently established 8.3-T-cell receptor (TCR)-beta transgen...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.1.34

    authors: Jun HS,Santamaria P,Lim HW,Zhang ML,Yoon JW

    更新日期:1999-01-01 00:00:00

  • Hepatocyte nuclear factor-4gamma: cDNA sequence, gene organization, and mutation screening in early-onset autosomal-dominant type 2 diabetes.

    abstract::The aim of this study was to investigate whether mutations in hepatocyte nuclear factor (HNF)-4gamma, a transcription factor homologous to HNF-4alpha, contribute to the etiology of early-onset type 2 diabetes. Linkage between diabetes and two polymorphic markers at the HNF-4gamma locus (D8S286 and D8S548) was evaluate...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.10.2099

    authors: Plengvidhya N,Antonellis A,Wogan LT,Poleev A,Borgschulze M,Warram JH,Ryffel GU,Krolewski AS,Doria A

    更新日期:1999-10-01 00:00:00

  • Divergent pathways of gene expression are activated by the RAGE ligands S100b and AGE-BSA.

    abstract::Activation of the receptor for advanced glycation end products (RAGE) reportedly triggers a variety of proinflammatory responses. However, our previous work revealed that RAGE-binding AGEs free of endotoxin were incapable of inducing vascular cell adhesion molecule-1 (VCAM-1) or tumor necrosis factor-alpha (TNF-alpha)...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.53.3.743

    authors: Valencia JV,Mone M,Zhang J,Weetall M,Buxton FP,Hughes TE

    更新日期:2004-03-01 00:00:00

  • Progression from insulitis to beta-cell destruction in NOD mouse requires L3T4+ T-lymphocytes.

    abstract::The identity of the cells responsible for beta-cell destruction in type I (insulin-dependent) diabetes is still uncertain. L3T4+ T-lymphocytes have a role in the initiation of insulitis and in damaging transplanted allogeneic islets in nonobese diabetic (NOD) mice. The role of L3T4+ T-lymphocytes in destruction of bet...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.37.8.1108

    authors: Charlton B,Mandel TE

    更新日期:1988-08-01 00:00:00

  • ALT-946 and aminoguanidine, inhibitors of advanced glycation, improve severe nephropathy in the diabetic transgenic (mREN-2)27 rat.

    abstract::The severe diabetic nephropathy that develops in the hypertensive transgenic (mRen-2)27 rat with streptozotocin (STZ) diabetes has previously been considered angiotensin II-dependent. Because metabolic pathways are also activated in the diabetic kidney, the present study aimed to determine whether renoprotection could...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.51.11.3283

    authors: Wilkinson-Berka JL,Kelly DJ,Koerner SM,Jaworski K,Davis B,Thallas V,Cooper ME

    更新日期:2002-11-01 00:00:00

  • Glycogen synthesis in human gastrocnemius muscle is not representative of whole-body muscle glycogen synthesis.

    abstract::The introduction of 13C magnetic resonance spectroscopy (MRS) has enabled noninvasive measurement of muscle glycogen synthesis in humans. Conclusions based on measurements by the MRS technique assume that glucose metabolism in gastrocnemius muscle is representative for all skeletal muscles and thus can be extrapolated...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.5.1277

    authors: Serlie MJ,de Haan JH,Tack CJ,Verberne HJ,Ackermans MT,Heerschap A,Sauerwein HP

    更新日期:2005-05-01 00:00:00

  • Altered hepatic and muscle substrate utilization provoked by GLUT4 ablation.

    abstract::Studies were conducted to explore altered substrate utilization and metabolism in GLUT4 null mice. Liver fatty acid synthase mRNA and fatty acid synthesis rates were dramatically increased in GLUT4 null mice compared with control mice and were supported by increased rates of the pentose phosphate pathway oxidative pha...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.4.935

    authors: Ranalletta M,Jiang H,Li J,Tsao TS,Stenbit AE,Yokoyama M,Katz EB,Charron MJ

    更新日期:2005-04-01 00:00:00

  • Diminished specific activity of cytosolic protein kinase C in sciatic nerve of streptozocin-induced diabetic rats and its correction by dietary myo-inositol.

    abstract::The impaired Na(+)-K(+)-ATPase activity in peripheral nerve from diabetic rats is prevented by dietary myo-inositol (MI) supplementation in vivo and corrected by protein kinase C (PKC) agonists in vitro, suggesting that PKC may mediate the effects of nerve MI depletion on Na(+)-K(+)-ATPase activity. However, little is...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.40.11.1545

    authors: Kim J,Rushovich EH,Thomas TP,Ueda T,Agranoff BW,Greene DA

    更新日期:1991-11-01 00:00:00

  • Autocrine action of adiponectin on human fat cells prevents the release of insulin resistance-inducing factors.

    abstract::The adipocyte hormone adiponectin is negatively correlated with obesity and insulin resistance and may exert an important antidiabetes function. In this study, primary human skeletal muscle cells were cocultured with human fat cells or incubated with adipocyte-conditioned medium in the presence or absence of the globu...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.54.7.2003

    authors: Dietze-Schroeder D,Sell H,Uhlig M,Koenen M,Eckel J

    更新日期:2005-07-01 00:00:00

  • Genetics of NIDDM in France: studies with 19 candidate genes in affected sib pairs.

    abstract::As part of an ongoing search for susceptibility loci for NIDDM, we tested 19 genes whose products are implicated in insulin secretion or action for linkage with NIDDM. Loci included the G-protein-coupled inwardly rectifying potassium channels expressed in beta-cells (KCNJ3 and KCNJ7), glucagon (GCG), glucokinase regul...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diab.46.6.1062

    authors: Vionnet N,Hani EH,Lesage S,Philippi A,Hager J,Varret M,Stoffel M,Tanizawa Y,Chiu KC,Glaser B,Permutt MA,Passa P,Demenais F,Froguel P

    更新日期:1997-06-01 00:00:00

  • Evidence for rapamycin toxicity in pancreatic β-cells and a review of the underlying molecular mechanisms.

    abstract::Rapamycin is used frequently in both transplantation and oncology. Although historically thought to have little diabetogenic effect, there is growing evidence of β-cell toxicity. This Review draws evidence for rapamycin toxicity from clinical studies of islet and renal transplantation, and of rapamycin as an anticance...

    journal_title:Diabetes

    pub_type: 杂志文章,评审

    doi:10.2337/db13-0106

    authors: Barlow AD,Nicholson ML,Herbert TP

    更新日期:2013-08-01 00:00:00

  • Role of apoptosis in failure of beta-cell mass compensation for insulin resistance and beta-cell defects in the male Zucker diabetic fatty rat.

    abstract::To define the mechanisms involved in the evolution of diabetes in the Zucker diabetic fatty (ZDF) rat, beta-cell mass and replication rates were determined by immunochemistry, point-counting morphometry, and 6-h 5-bromo-2'-deoxyuridine (BrdU) incorporation. The beta-cell mass in 5- to 7-week-old prediabetic ZDF rats (...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.47.3.358

    authors: Pick A,Clark J,Kubstrup C,Levisetti M,Pugh W,Bonner-Weir S,Polonsky KS

    更新日期:1998-03-01 00:00:00

  • The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration.

    abstract::Islet duodenal homeobox 1 (IDX-1/PF-1/STF-1/PDX-1), a homeodomain protein that transactivates the insulin promoter, has been shown by targeted gene ablation to be required for pancreatic development. After 90% pancreatectomy (Px), the adult pancreas regenerates in a process recapitulating embryonic development, starti...

    journal_title:Diabetes

    pub_type: 杂志文章

    doi:10.2337/diabetes.48.3.507

    authors: Sharma A,Zangen DH,Reitz P,Taneja M,Lissauer ME,Miller CP,Weir GC,Habener JF,Bonner-Weir S

    更新日期:1999-03-01 00:00:00