Abstracts Archive

  Insulin-dependent diabetes mellitus (Type 1 diabetes, T1D) is an autoimmune disease where autoreactive T lymphocytes destroy pancreatic beta cells. Common human autoimmune diseases show quantitative or qualitative T regulatory (Treg) defects. We previously reported a defect in CD4+ Tregs cell pro...

Background: Induction of Tregs in the gut can promote tolerance towards pancreas associated antigens in type 1 diabetes. In this study, we induced colonic Tregs (cTregs) by administering sodium butyrate in NOD mice and analyzed their migratory potential towards pancreas and pancreatic lymph nodes (P...

Background: MicroRNAs are a class of small non-coding RNAs that regulate gene expression, which are involved in β-cell function and differentiation; their alteration may contribute to the development of type 1 diabetes(T1D). The aim of this study was to analyze their expression profile in pancreati...

Aim: The majority of people with long duration (>5years) T1D have a small number of functioning beta-cells, and a small proportion of these have relatively high C-peptide despite longstanding T1D. However, the clinical correlates and mechanisms for persistent beta cell function are not known...

Background: The single residue polymorphism at b57 in HLA-DQ8 and I-Ag7 is the dominant genetic feature of T1D. The molecular mechanisms supporting this association are unknown. We had shown that a “P9 switch model” of T cell recognition was controlled by b57 for the recognition of HEL antigen; ...

 Type 1 diabetes is an autoimmune disease that results from autoreactive destruction of insulin producing beta cells and the pathogenesis is characterized by chronic infiltration of immune cells in islets. Stimulator of interferon genes (STING), is a central hub for cytosolic nucleic acid sensing i...

Background Islet transplantation in patients with type 1 diabetes can be associated to re-activation of quiescent autoreactive T cells and standard immuno-suppression has limited capacity to control autoimmunity recurrence. Once activated, autoreactive T cells upregulate the glucose transporter GLUT...

The risk of developing type 1 diabetes is decreased in children born to mothers with type 1 diabetes as compared to children with a father or sibling with type 1 diabetes. We hypothesized that protection is provided by the increased proinsulin and insulin production by the fetus during a maternal ty...

Background DNA including self DNA binds to Toll-like receptor 9 (TLR9) as a nucleotide-sensing receptor. TLR9 is expressed mostly on antigen presenting cells (APCs) and plays an important role in host immune response to pathogens as well as to self antigens. We have previously shown that TLR9-defici...

Background Gold nanoparticles (GNP) are used as a means of delivering drugs as well as proteins and peptides, particularly for cancer therapy. However, comparatively little is known regarding the use of gold nanoparticles for autoimmune disease therapy. The aim of our study was to test the effects...

Background: Primary prevention of type 1 diabetes (T1D) requires early intervention in genetically at-risk infants. Neonates and infants who are at increased risk to develop type 1 diabetes can be identified using genetic markers. The Global Platform for the Prevention of Autoimmune Diabetes (GPPAD)...

Background: The reeducation of the immune system is crucial to tackle autoimmunity in type 1 diabetes (T1D). Since self–tolerance is induced by apoptotic cell clearance (a process known as efferocytosis), a nanotherapy consisting of liposomes rich in phosphatidylserine (PS) encapsulating beta–ce...

BACKGROUND: Antigen-specific immunotherapies (ASIT) may rely on targeting as many disease-relevant T cells as possible for efficacy. This clearly requires an appropriate delivery system that protects antigens or antigen-encoding vectors from degradation and facilitates their drainage to lymphoid tis...

BACKGROUND: Antigen-presenting cell (APC) populations in pancreatic lymph nodes (PLNs) remain poorly defined, and whether phenotypic or functional alterations in these populations contribute to the imbalance in T cell responses in human PLNs is yet to be determined. Furthermore, alternative APC subs...

Human ex vivo regulatory T cells (Treg) are commonly distinguished from conventional T cells (Tconv) by their expression of CD4+ CD25+, FOXP3+ and the lack of CD127. However, upon stimulation Tconv can up- or downregulate Treg characteristic markers making it difficult to distinguish effector and ...

IL-2 is a promising therapy for autoimmune type 1 diabetes (T1D), but the short half-life of injected IL-2 (less than 6 minutes) necessitates frequent injections and limits effective tissue exposure to IL-2. We have developed an injectable hydrogel for delivery of sustained release IL-2. This platf...

Islet autoimmunity, the presymptomatic phase of type 1 diabetes (T1D), is characterized by aberrations in immune activation versus T-cell tolerance. However, the molecular underpinnings remain poorly understood. MiRNAs regulate multiple targets and thereby can alter complex cellular states. During r...

  T cell exhaustion is a dysfunctional state that has been associated with reduced disease activity in autoimmune disorders including type 1 diabetes (T1D). Hence, the induction of T cell exhaustion might be an attractive approach to impair self-reactive effector memory T cells and halt autoimmune ...

Neonatal period is a critical window when central tolerance is established in an Autoimmune Regulator (Aire). However, not all self-antigens are expressed downstream of Aire and tolerance to some tissue restricted antigens might rely in part on peripheral dendritic cells (DCs). The relative contrib...

  Background. Type 1 diabetes (T1D) is an autoimmune disease in which the immune system destroys insulin-producing pancreatic beta-cells. Although pro-insulin is probably the primary autoantigen, other non-beta-cell specific proteins behave as autoantigens. Data indicate that such proteins can ...

The long-term success of islet transplantation as a diabetes treatment depends on halting underlying recurrence of autoimmunity driven by pre-primed autoreactive effector T cells. Low-dose anti-CD3 monoclonal antibodies combined with live Lactococcus lactis secreting proinsulin and IL-10 (LL-PINS+IL...

Background: Insulin is an essential autoantigen in human and murine type 1 diabetes. Thymic negative selection is critical for the removal of self-reactive cells, while peripheral regulation maintains tolerance to self-antigen. As low-affinity autoreactive cells escape central tolerance, peripheral ...

Background. Tolerogenic vaccinations using beta-cell antigens (Ags) targeted by autoimmune T-cells are attractive for T1D prevention due to their selectivity and safety, but have not hold their promise in clinical trials. This is probably due to the late time of intervention, once the autoimmune rea...

Type 1 diabetes (T1D) is a complex disease that is influenced by various genetic and environmental factors. Studies have shown that a dysregulation in iron metabolism contributes to the development of diabetes, and higher dietary iron increases the risk of developing T1D. The underlying mechanism, h...

  CD8+ T cells are key player of the adaptive immune response. Improving our understanding of antigen-specific T cell responses on the single cell level will be crucial for the development of highly effective future vaccines and a necessity to resolve or minimize errant immunity in autoimmune disea...

  We recently established that hybrid insulin peptides (HIPs), formed spontaneously in islet beta-cells by fusion of insulin C-peptide fragments to peptides of Chromogranin A (ChgA) or Islet Amyloid Polypeptide (IAPP), are ligands for diabetogenic CD4 T cell clones. The goal of this study was t...

  Samuel I. Blum1, Ashley R. Burg1, Yi-Guang Chen2 and Hubert M. Tse1  1Department of Microbiology, Comprehensive Diabetes Center, University of Alabama at Birmingham, Birmingham, AL  2Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI While microbial infections can...

  Under particular circumstances human leukocyte antigen (HLA) class I molecules may present peptides derived from extracellular proteins to CD8+ T cells (a process termed cross-presentation) to induce or maintain cytotoxic T cell responses (CTL). This interaction is likely to be important in autoi...

BACKGROUND: Antigen-specific tolerance has not yet been achieved in Type 1 diabetes (T1D) patients, who harbor diabetogenic T cells reacting against multiple beta-cell antigens. Plasmid DNA (pDNA)-encoding such antigens have been evaluated with the goal to achieve tolerance, and have the advantages ...